Efficacy of Rifaximin Combined with Probiotics in the Treatment of Functional Diarrhea: A Prospective Cohort Study

Efficacy of Rifaximin Combined with Probiotics in the Treatment of Functional Diarrhea: A Prospective Cohort Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Efficacy of Rifaximin Combined with Probiotics in the Treatment of Functional Diarrhea: A Prospective Cohort Study Jing Zhou, Guo-Jian Yin, Yu Xin Liu, Feng Jie Ji This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8650251/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Functional diarrhea (FDr) is a common functional gastrointestinal disorder characterized by chronic or recurrent loose stools without organic pathology. It has a worldwide prevalence and exerts a substantial negative impact on patients’ quality of life. Current therapeutic options for FDr remain limited and are often unsatisfactory. Rifaximin is a minimally absorbed, broad-spectrum, gut-targeted antibiotic with modulatory effects on intestinal microbiota and mucosal inflammation. While rifaximin has demonstrated efficacy in irritable bowel syndrome with diarrhea, robust evidence for its therapeutic role in FDr is lacking. Aims This prospective cohort study aimed to investigate the efficacy and safety of rifaximin combined with probiotics in improving clinical symptoms and reducing recurrence in patients with FDr. Methods From April 2022 to June 2024, 121 patients diagnosed with FDr at the Department of Gastroenterology, the Second Affiliated Hospital of Soochow University, were consecutively enrolled. Patients chose either rifaximin combined with probiotics (exposed group) or probiotics alone (unexposed group). All patients received probiotics as baseline therapy, while the exposed group additionally received rifaximin. Symptom changes, including mean daily stool frequency, stool consistency, urgency, incomplete evacuation, flatulence, borborygmi, and presence of mucus or foam, were recorded at baseline, at the end of treatment, and one month after treatment. Primary outcomes were improvements in stool frequency and stool consistency. Secondary outcomes included changes in other gastrointestinal symptoms and overall response rate. Statistical analysis was performed using chi-square and paired t-tests, with P < 0.05 considered significant. Results At the end of treatment, both groups showed significant improvement compared with baseline across all evaluated symptoms. Between-group comparison demonstrated that the rifaximin group achieved significantly greater improvement in stool frequency and flatulence (P < 0.05). At one month post-treatment, partial symptom relapse was observed, but both groups maintained better outcomes compared with baseline. The rifaximin group exhibited significantly greater improvement in stool frequency, stool consistency, and flatulence than the control group (P < 0.05). The overall response rate was 87.1% versus 72.9% at treatment completion (P < 0.05) and 77.4% versus 54.2% at one month post-treatment (P < 0.05). No serious adverse events were reported. Conclusion Rifaximin combined with probiotics effectively improves stool frequency, stool consistency, and flatulence in patients with FDr, reduces recurrence, and enhances quality of life. The regimen was well tolerated and may represent a promising therapeutic option for FDr, warranting further validation in randomized controlled trials. chronic diarrhea functional diarrhea rifaximin probiotics gut microbiota Figures Figure 1 Core Tip Functional diarrhea (FDr) lacks effective treatment strategies. This prospective cohort study evaluated rifaximin, a non-absorbable antibiotic targeting intestinal microbiota, combined with probiotics in FDr patients. The regimen significantly improved stool frequency, stool consistency, and flatulence, with sustained benefits one month post-treatment and a reduced recurrence rate compared with probiotics alone. No serious adverse events were observed. These findings suggest that rifaximin plus probiotics is a safe and effective therapeutic option for FDr, offering novel insights into microbiota-targeted management of functional gastrointestinal disorders. Background Functional diarrhea (FDr) is a common functional gastrointestinal disease characterized by persistent or recurrent loose, pasty, or watery stools, typically lasting for more than six months [ 1 ] . An internet based survey found that FDr affects about 4.7% of the global population, and the incidence rate in China is slightly higher, 5.6% [ 2 ] . At present, the treatment intervention of FDr mainly focuses on relieving symptoms and improving quality of life. These intervention measures include adjusting diet and lifestyle, medication treatment for diarrhea (such as loperamide), alternative and complementary therapies (including prebiotics and probiotics), cognitive-behavioral therapy and other psychosocial interventions, as well as traditional Chinese medicine [ 3 , 4 ] . Probiotics demonstrate the ability to regulate gut microbiota balance and enhance intestinal barrier defense [ 5 ] , and hinder pathogen growth [ 6 ] . Many studies [ 7 – 9 ] have confirmed the efficacy of probiotics in improving FDr symptoms, and specific combinations of probiotic strains may provide more benefits [ 10 ] . Rifaximin, a broad-spectrum antibiotic exerting a localized effect on intestinal flora without systemic absorption, has demonstrated its effectiveness in managing gastrointestinal disorders. It can significantly alleviate gastrointestinal symptoms such as diarrhea, abdominal pain, and bloating, reduce the risk of systemic side effects, and contribute to enhancing the quality of life [ 11 , 12 ] . Although rifaximin has been proven safe and effective in various situations [ 13 , 14 ], the conclusive evidences supporting its specific use in FDr treatment remains elusive [ 1 ] . The aim of this study is to evaluate the efficacy and safety of the combination of rifaximin and probiotics in the treatment of FDr. Patients receiving combined treatment with live Bacillus licheniformis and Lactobacillus acidophilus were assigned to the unexposed group, while patients receiving treatment plus with rifaximin formed the exposed group. Methods Study Design and Setting This was a non-randomized, prospective cohort study conducted at the Gastroenterology outpatient department of the Second Affiliated Hospital of Soochow University (Suzhou, China) from April 2022 to February 2024. Patients were provided the option to choose between receiving rifaximin combined with probiotics (exposed group) or probiotics alone (unexposed group) after being informed about the potential benefits and risks of both treatments by the attending physician. The decision was based on patient preference and informed consent. Participants Adults aged 18–65 years with a diagnosis of functional diarrhea (FDr) according to the Rome IV criteria were eligible for inclusion. Patients were excluded if they had evidence of organic bowel disease (e.g., inflammatory bowel disease, colon cancer, ischemic bowel disease), severe organ failure (cardiac, renal, hepatic), advanced malignancy, or any conditions that could interfere with their ability to understand or comply with the study protocol, such as severe mental illness or cognitive impairments. Inclusion Criteria Age between 18 and 65 years; Diagnosed with FDr according to Rome IV criteria; Ability to understand the research details and voluntarily sign informed consent; No FDr-related medication within two weeks prior to enrollment. Exclusion Criteria Colonoscopy indicating inflammatory bowel disease, colon cancer, ischemic bowel disease, or other organic bowel diseases; Severe cardiovascular, renal, hepatic, or other critical organ failure; Advanced malignancy or severe cachexia; Pregnancy or breastfeeding status; Allergy to rifaximin or any components of the probiotics used; Severe mental illness or cognitive impairments preventing understanding of or compliance with the study protocol; History of alcohol or substance abuse. Ethics Statement The study was approved by the Ethics Committee of the Second Affiliated Hospital of Soochow University (Approval No. LC2024009). All participants provided written informed consent before enrollment. The study was conducted in accordance with the 2013 revision of the Declaration of Helsinki. Intervention Patients in the exposed group received rifaximin (400 mg twice daily for 6 consecutive days), Bacillus licheniformis (0.25g three times daily for 12 days), and Lactobacillus acidophilus (0.5g three times daily for 12 days). Patients in the unexposed group received the same probiotic regimen without rifaximin. The medications used in the study were: Rifaximin : Brand name: 'Xifushen', 0.2g tablets (12 tablets per box), manufactured by Alfa Sigma Co., Ltd., approval number H20181212, valid for 36 months, stored in a light-protected, tightly sealed container. Bacillus licheniformis : Brand name: 'Zhengchangsheng', 0.25g capsules (36 capsules per bottle), manufactured by Northeast Pharmaceutical Group Shenyang No.1 Pharmaceutical Co., Ltd., approval number National Medicine Zhunzi S20073008, valid for 24 months, stored at room temperature in a light-protected, dry place. Lactobacillus acidophilus : Brand name: 'Yijinkang', 0.5g tablets (24 tablets per box), manufactured by Tonghua Jinma Pharmaceutical Group Co., Ltd., approval number National Medicine Zhunzi H10940114, valid for 24 months, stored in a light-protected, sealed container at room temperature. Efficacy Endpoints As no clinical trials have specifically evaluated rifaximin in functional diarrhea to date, the efficacy endpoints in this study were selected by referring to outcome measures widely adopted in rifaximin clinical trials for diarrhea-predominant irritable bowel syndrome [ 14 – 17 ] . Primary Endpoint The primary efficacy endpoint was the change from baseline (CFB) in the mean number of bowel movements per day (BMD) at the end of treatment (Day 12 ± 1) and one month post-treatment (Day 30 ± 5). BMD was calculated as the average number of bowel movements recorded over three consecutive days. Secondary Endpoints Change from baseline in stool consistency assessed by the Bristol Stool Form Scale (BSFS) [ 16 ] (types 1–7) at the end of treatment and one month after treatment; Change from baseline in urgency of defecation and incomplete evacuation, classified into five severity grades: grade 0 (not at all), grade 1 (mildly), grade 2 (moderately), grade 3 (greatly), and grade 4 (extremely); Presence or absence of frequent flatulence, borborygmi, mucus in stool, and frothy stool (recorded as yes/no); Overall efficacy, categorized as cured, markedly effective, effective, or ineffective, based on symptom improvement (Table 1 ). Table 1 Evaluation Criteria for the Overall Therapeutic Effect of Rifaximin Effect Evaluation Criteria Cure 1–2 bowel movements daily, well-formed stool, and most symptoms resolved. Marked Effect Fewer than 3 bowel movements daily, nearly formed stool unaffected by external factors, with significant symptom improvement. Effective Reduced frequency of bowel movements, nearly formed but may vary due to external factors, some symptom improvement. Ineffective No notable change in the frequency or consistency of bowel movements; possible worsening and no significant symptom improvement. Follow-up and Data Collection Follow-up assessments were conducted at the end of treatment (Day 12 ± 1) and one month after treatment (Day 30 ± 5) through clinical surveys, telephone calls, or online questionnaires. Stool hardness was documented via photographs provided by the patients, using a reference image for consistency. Healthcare providers verified the photographs during follow-up visits. Detailed records of any adverse events were promptly documented and managed. Statistical Analysis Data were analyzed using IBM SPSS Statistics version 27.0 (IBM Corp., Armonk, NY). For continuous data, normality was assessed using the Shapiro–Wilk test. Normally distributed data were presented as mean ± standard deviation and analyzed using t-tests. Non-normally distributed data were presented as medians (interquartile ranges) and analyzed using nonparametric tests (Mann-Whitney U test). Categorical data were described using frequencies and percentages and analyzed using chi-square or Fisher’s exact test. Repeated measures data were evaluated using ANOVA or the generalized estimating equation (GEE) approach for correlated outcomes.The significance level was set at α = 0.05. For multiple comparisons, a Bonferroni correction was applied to adjust for family-wise error rate. A p-value < 0.05 was considered statistically significant. Results Patient Demographics and Baseline Characteristics A total of 133 patients were enrolled in this study: 69 in the exposed group (rifaximin + probiotics) and 64 in the unexposed group (probiotics only). After exclusion (due to poor compliance, temporary work changes, or loss to follow-up), 121 patients (62 in the exposed group and 59 in the unexposed group) completed the study and follow-up. Baseline demographic and clinical characteristics were similar between the two groups (Table 2 ). The mean age of participants was 43.81 ± 8.73 years in the exposed group and 42.36 ± 11.60 years in the unexposed group (P = 0.44). The majority of participants were male (66.9%). The median disease duration was 5 years in both groups, and there were no significant differences in baseline symptom severity (BMD, stool hardness, urgency, incomplete evacuation, flatulence, borborygmi, mucus in stool, and frothy stool) between the two groups (P > 0.05). Table 2 Baseline characteristics of participants, by group. Characteristic Exposed Group (n = 62) Unexposed group(n = 59) P Sex, n (%) Male 42(67.74%) 39(66.10%) 0.848 Female 20(32.26%) 20(33.90%) Age,y 43.81 ± 8.73 42.36 ± 11.60 0.44 Height, cm 170.05 ± 5.99 169.12 ± 9.65 0.528 weight, kg 71.36 ± 9.66 70.58 ± 14.79 0.734 BMI, n (%) 0.338 Thin BMI<18.5 0 1(1.69%) Normal 18.5 ≤ BMI<24 22(35.48%) 24(40.68%) Overweight 24 ≤ BMI 28 9(14.52%) 6(10.17%) Disease duration, y 5(2 ~ 10) 5(2 ~ 10) 0.68 Hypertension, n (%) 11(17.74%) 15(25.4%) 0.304 Diabetes, n (%) 2(3.23%) 3(5.08%) 0.674 Smoking, n (%) 10(16.13%) 11(18.6%) 0.715 Alcohol consumption, n (%) 10(16.13%) 13(22.0%) 0.408 Cholecystectomy, n (%) 4(6.45%) 3(5.08%) 1 Main Symptoms BMD 2.25(2, 3.125) 2.5(2, 3.5) 0.167 Secondary symptoms Stool hardness score, n (%) 0.979 6 44(71.0%) 42(71.2%) 7 18(29.0%) 17(28.8%) Other symptoms Urgency of defecation score, n (%) 0.502 0 16(25.8%) 16(27.1%) 1 9(14.5%) 7(11.9%) 2 21(33.9%) 15(25.4%) 3 13(21.0%) 15(25.4%) 4 3(4.8%) 6(10.2%) Incomplete evacuation score, n (%) 0.701 0 22(35.5%) 22(37.3%) 1 14(22.6%) 8(13.6%) 2 16(25.8%) 17(28.8%) 3 9(14.5%) 12(20.3%) 4 1(1.6%) 0 Frequent flatulence, n (%) 0.336 yes 43(69.35%) 36(61.02%) no 19(30.65%) 23(38.98%) Borborygmi, n (%) 0.682 yes 24(38.71%) 25(42.37%) no 38(61.29%) 34(57.6%) Mucus in stool, n (%) 0.563 yes 19(30.65%) 21(35.59%) no 43(69.35%) 38(64.41%) Frothy stool, n (%) 0.436 yes 15(24.19%) 18(30.51%) no 47(75.81%) 41(69.49%) Primary Endpoint: Bowel Movements per Day (BMD) The mean BMD significantly decreased from baseline in both groups at the end of treatment and one month after treatment (Table 3 ). Table 3 Mean number of bowel movements per day (BMD) and stool characterization statistics W 0 W 1 W 2 Comparison within exposed group Comparison within unexposed group Comparison between groups Mean Difference (95% confidence interval) P Mean Difference (95% confidence interval) P Mean Difference (95% confidence interval) P BMD Exposed group 2.25 (2, 3.125) 1.5 (1, 2) 1.5 (1, 2.125) -1.073 (-1.261, -0.884) P 1 <0.001 -0.958 (-1.236, -0.679) P 3 <0.001 -0.368 (-0.627, -0.109) P 5 =0.005 Unexposed group 2.5 (2, 3.5) 2 (1.5, 2.5) 2.5 (1.5, 3) -0.887 (-1.101, -0.673) P 2 <0.001 -0.568 (-0810, -0.325) P 4 <0.001 -0.572 (-0.885, -0.259) P 6 <0.001 Stool hardness Exposed group 6 (6, 6) 4 (4, 5) 4 (4, 6) -1.855 (-2.154, -1.555) P 1 <0.001 -1.559 (-1.930, -1.189) P 3 <0.001 -0.388 (-0.848, 0.068) P 5 =0.096 Unexposed group 6 (6, 7) 5 (4, 6) 6 (5, 6) -1.661 (-1.993, -1.330) P 2 <0.001 -1.153 (-1.537, -0.768) P 4 <0.001 -0.602 (-1.088, -0.115) P 6 =0.015 W 0 : before medication; W 1 : at the end of treatment; W 2 : 1 month after the end of treatment. P 1 is the within-group comparison of the exposed group at the end of treatment, P 2 is the within-group comparison of the exposed group at 1 month after the end of treatment, P 3 is the within-group comparison of the unexposed group at the end of treatment, P 4 is the within-group comparison of the unexposed group at 1 month after the end of treatment. P 5 is the between-group comparison of the exposed group and the unexposed group at the end of treatment. P 6 is a between-group comparison between the exposed group and the unexposed group 1 month after the end of drug In the exposed group, BMD decreased from 2.25 (2.00, 3.125) at baseline to 1.5 (1.00, 2.00) at the end of treatment (P < 0.001), and to 1.5 (1.00, 2.125) at one month post-treatment (P < 0.001). In the unexposed group, BMD decreased from 2.5 (2.00, 3.50) at baseline to 2.0 (1.50, 2.50) at the end of treatment (P < 0.001), and to 2.5 (1.50, 3.00) at one month post-treatment (P < 0.001). Between-group comparison at the end of treatment revealed a greater reduction in BMD in the exposed group (mean difference: −0.368, P = 0.005), with a more significant improvement one month after treatment (mean difference: −0.572, P < 0.001). Secondary Endpoint 1: Stool Hardness Both groups showed significant improvement in stool hardness from baseline at the end of treatment and one month after treatment (Table 3 ). In the exposed group, stool hardness decreased from 6 (6.00, 6.00) at baseline to 4 (4.00, 5.00) at the end of treatment (P < 0.001), and to 4 (4.00, 6.00) one month post-treatment (P < 0.001). In the unexposed group, stool hardness decreased from 6 (6.00, 7.00) at baseline to 5 (4.00, 6.00) at the end of treatment (P < 0.001), and to 6 (5.00, 6.00) at one month post-treatment (P < 0.001). However, there was no significant difference in stool hardness between the two groups at the end of treatment (P = 0.096), though a significant difference was observed one month after treatment (mean difference: −0.602, P = 0.015). Secondary Endpoint 2: Gastrointestinal Symptoms Urgency of Defecation and Incomplete Evacuation Both groups experienced improvements in urgency of defecation and incomplete evacuation at the end of treatment and one month post-treatment (Fig. 1 ). However, no significant difference was observed between the two groups (P > 0.05 for both time points), indicating that rifaximin had a limited effect on these symptoms. Flatulence, Borborygmi, Mucus in Stool, and Frothy Stool There were significant differences between the groups in terms of flatulence and borborygmi, but no significant differences for mucus in stool and frothy stool (Table 4 ). Table 4 Statistical analysis of the efficacy of other symptoms W 0 W 1 W 2 Within Group Comparison Between Group Comparison RR P RR P Frequent flatulence Exposed group(n = 62) YES 43(69.35%) 10(6.13%) 15(24.19%) 0.23 P 1 <0.001 0.47 P 5 =0.026 NO 19(30.65%) 52(83.87%) 47(75.81%) 0.35 P 2 <0.001 Unexposed group(n = 59) YES 36(61.02%) 20(33.90%) 27(45.76%) 0.56 P 3 <0.001 0.53 P 6 =0.008 NO 23(38.98%) 39(66.10%) 32(54.24%) 0.75 P 4 =0.004 Borborygmi Exposed group(n = 62) YES 24(38.7%) 8(12.9%) 13(20.97%) 0.33 P 1 <0.001 0.76 P 5 =0.533 NO 38(61.3%) 54(87.1%) 49(79.03%) 0.54 P 2 =0.015 Unexposed group(n = 59) YES 25(42.4%) 10(16.9%) 18(30.5%) 0.4 P 3 <0.001 0.69 P 6 =0.232 NO 34(57.6%) 49(83.1%) 41(69.5%) 0.72 P 4 =0.005 Mucus in stool Exposed group(n = 62) YES 19(30.6%) 9(14.5%) 10(16.1%) 0.47 P 1 <0.001 0.95 P 5 =0.909 NO 43(69.4%) 53(85.5%) 52(83.9%) 0.53 P 2 =0.005 Unexposed group(n = 59) YES 21(35.6%) 9(15.3%) 14(23.7%) 0.43 P 3 <0.001 0.68 P 6 =0.297 NO 38(64.4%) 50(84.7%) 45(76.3%) 0.67 P 4 =0.016 Frothy stool Exposed group(n = 62) YES 15(24.2%) 7(11.3%) 8(12.9%) 0.47 P 1 =0.003 0.83 P 5 =0.705 NO 47(75.8%) 55(88.7%) 54(87.1%) 0.53 P 2 =0.006 Unexposed group(n = 59) YES 18(30.5%) 8(13.6%) 11(18.6%) 0.44 P 3 =0.003 0.69 P 6 =0.388 NO 41(69.5%) 51(86.4%) 48(81.4%) 0.61 P 4 =0.016 W 1 : at the end of treatment; W 2 : 1 month after the end of treatment. P 1 is the within-group comparison of the exposed group at the end of treatment, P 2 is the within-group comparison of the exposed group at 1 month after the end of treatment, P 3 is the within-group comparison of the unexposed group at the end of treatment, P 4 is the within-group comparison of the unexposed group at 1 month after the end of treatment. P 5 is the between-group comparison of the exposed group and the unexposed group at the end of treatment. P 6 is a between-group comparison between the exposed group and the unexposed group 1 month after the end of drug. Flatulence : In the exposed group, the relative risk (RR) at the end of treatment was 0.23 (P < 0.001), and 0.35 after one month of treatment (P < 0.001). In the unexposed group, the RR at the end of treatment was 0.56 (P < 0.001), and 0.75 one month post-treatment (P = 0.004). The between-group comparison showed a statistically significant difference at both time points (end of treatment: P = 0.026; one month post-treatment: P = 0.008). Borborygmi In the exposed group, the RR was 0.33 (P < 0.001) at the end of treatment and 0.54 (P = 0.015) one month post-treatment. In the unexposed group, the RR was 0.40 (P < 0.001) at the end of treatment and 0.72 (P 0.05). Mucus in Stool In the exposed group, RR was 0.47 (P < 0.001) at the end of treatment and 0.53 (P = 0.005) one month post-treatment. In the unexposed group, RR was 0.43 (P 0.05). Frothy Stool The exposed group showed an RR of 0.47 (P = 0.003) at the end of treatment and 0.53 (P = 0.006) one month post-treatment. In the unexposed group, RR was 0.44 (P = 0.003) at the end of treatment and 0.61 (P = 0.016) one month post-treatment. Again, there was no significant difference between the two groups (P > 0.05). Overall Efficacy At the end of treatment, the overall response rate (cured, markedly effective, and effective) was significantly higher in the exposed group compared to the unexposed group (87.1% vs. 72.9%, P = 0.021). This trend continued one month post-treatment, with the exposed group showing a greater improvement (77.4% vs. 54.2%, P = 0.003) (Table 5 ). Table 5 Statistical assessment of efficacy at the end of treatment and at 1 month after the end of treatment Cure Marked Effect Effective Ineffective Overall effective rate P W 1 Exposed group 10(16.1%) 31(50.0%) 13(21.0%) 8(12.9%) 87.10% 0.021 Unexposed group 12(20.3%) 14(23.7%) 17(28.8%) 16(27.1%) 72.90% W 2 Exposed group 11(17.7%) 23(37.1%) 14(22.6%) 14(22.6%) 77.40% 0.003 Unexposed group 9(15.3%) 7(11.9%) 16(27.1%) 27(45.8%) 54.20% Overall effective rate = (cured + apparent + effective)/total. A: exposed group; B: unexposed group ;W1: at the end of treatment; W 2 : 1 month after the end of treatment. Safety No serious adverse events were reported during the study. Both treatment regimens were well tolerated, and there were no significant differences in adverse events between the two groups. Discussion The findings of this study suggested that the combination of rifaximin and probiotics for a 12 day course was a safe and effective treatment option for FDr patients, according to the definition of Rome IV criteria. The observed improvement in gastrointestinal (GI) symptoms indicated that rifaximin might serve as a feasible therapeutic approach for FDr, with its benefits lasting for one month after the end of treatment. The Rome IV diagnostic criteria distinguish FDr from irritable bowel syndrome with diarrhoea (IBS-D) primarily by the absence of recurrent abdominal pain in FDr, focusing primarily on chronic diarrhoea. Both of these diseases are classified as functional gastrointestinal disorders, with similar physiological and psychological manifestations. According to Prashant Singh [ 18 ] et al., although the frequency of diarrhea is comparable, IBS-D patients experience a higher proportion and severity of abdominal pain compared to those with FDr. In addition, the incidence of anxiety, depression, and sleep disorders is similar in these two situations. Yan-Fang Zhao [ 19 ] et al. noticed that the fecal characteristics of FDr and IBS-D are similar. However, the characteristics of IBS-D are more frequent bowel movements (> 3 times), urgency of bowel movements, and bloating. Investigations based on the Rome II criteria suggest that some cases initially diagnosed wth IBS-D might actually meet the criteria for FDr under newer guidelines. Studies have shown that there was a significant difference in the incidence rate when using Rome III and Rome IV criteria for diagnosis [ 20 ] . Given their similarities, it has been proposed that FDr and IBS-D might represent different stages of the same disease spectrum, ranging from mild/painless chronic diarrhea to painful chronic diarrhea [ 18 ] . 15%-20% of IBS-D cases are linked to gut microbiota, and dysbiosis can affect motility, immune function, and barrier integrity [ 21 – 23 ] . Specific gut bacteria are associated with the severity of symptoms [ 24 ] . I M Carroll [ 25 ] et al. found that compared to healthy subjects, IBS-D patients had significantly more abundance of Enterobacteriaceae, while fecal Enterococcus was significantly reduced, and the overall abundance of bacteria was lower. Saffouri GB [ 26 ] et al. reported that FDr is associated with changes in gut microbiota, including small intestinal bacterial overgrowth (SIBO). Chronic diarrhea in both cases may involve multiple pathogenic mechanisms, with dysbiosis of the gut microbiota being a common factor. The American Gastroenterological Association's 2022 guidelines recommend various treatment options for FDr, including antidiarrhoeal agents, 5-HT3 receptor antagonists, probiotics, and prebiotics. As is well known, probiotics such as lactobacilli and bifidobacteria can protect intestinal epithelial cells, enhance barrier function, and regulate intestinal microbiota [ 27 ] . A meta-analysis has shown that probiotics can improve stool frequency, morphology, and related symptoms in patients with diarrhoea [ 28 ] . A specific study on Lactobacillus plantarum CCFM1143 demonstrated its ability to alleviate chronic diarrhoea by modulating gut microbiota and reducing inflammation [ 29 ] . Evidence supports using specific probiotic combinations for treatment. Based on guidelines, literature review, and clinical experience, our center selected a combination of Lactobacillus acidophilus complex and Bacillus licheniformis for clinical research. This study indicated that the combined use of these two probiotics significantly improved patients' symptoms compared to baseline. This mechanism may involve Bacillus licheniformis restoring gut microbiota balance and reducing inflammation, while Lactobacillus acidophilus contains four types of bacteria that can increase bacterial abundance. A study showed that Bacillus licheniformis reversed ceftriaxone sodium-induced dysbiosis and intestinal inflammation in mice, promoting beneficial bacteria growth (e.g., fungi and Lactobacillus) [ 30 ] . Another study demonstrated its ability to repair intestinal barrier damage and restore tight junction protein expression after antibiotic treatment, which is crucial for maintaining intestinal integrity and function. The efficacy and safety of rifaximin in the treatment of IBS-D have been confirmed, but its efficacy on FDr is still unclear due to limited clinical research. In two phase 3 randomized double-blind trials with identical designs, compared with the placebo group, the proportion of IBS-D patients who received treatment with rifaximin 550 mg three times a day for 14 days had a higher rate of symptom relief (40.7% vs. 31.7%, p < 0.01) [ 15 ] . In another randomized double-blind trial evaluating repeated treatment with the same regimen, the safety of rifaximin was comparable to placebo [ 31 ] . Our center has accumulated rich clinical experience in the treatment of FDr over the past period. Before starting the study, we decided on a treatment regimen of rifaximin 400 mg twice daily for 6 consecutive days, considering guideline recommendations, relevant literature, and patient affordability. Patients were fully informed about the differences between the two treatment regimens before starting therapy and have the option to choose whether or not to receive treatment with rifaximin. The results of this study indicated that the combination of rifaximin with Lactobacillus acidophilus and Bacillus licheniformis was effective in treating FDr. This combination showed better efficacy than using the probiotics alone, suggesting rifaximin's potential for FDr treatment. Rifaximin can bind to the DNA-dependent RNA polymerase b subunit of target bacteria, inhibiting bacterial RNA synthesis [ 32 ] . IBS-D could be treated with rifaximin by regulating the intestinal flora [ 33 ] . It can promote the growth of beneficial bacteria such as bifidobacteria and lactobacilli without significantly altering the overall composition of the gut microbiota [ 34 – 36 ] . Additionally, rifaximin stabilizes epithelial cells and reduces intestinal inflammation [ 37 ] . The mechanism behind rifaximin's effectiveness with probiotics may involve normalizing gut flora, reducing inflammation, and restoring barrier function. However, studies show that rifaximin’s effect on flora are limited and short-lived [ 33 , 38 , 39 ] . Some patients experienced symptom recurrence after one month of treatment. Our next step will be to investigate the effects of repeated rifaximin treatments for FDr, as well as longer-term follow-up. Limitations of this study include its single-center design and small sample size, which reduce the reliability of the findings. There was no unexposed group receiving rifaximin alone, and non-randomization was a limited factor. This study did not fully explore the specific mechanisms by which the combination of rifaximin and probiotics may benefit patients diagnosed with FDr.. Overall, the combination of rifaximin and probiotics is safe and effective for short-term treatment of FDr, but it is necessary to validate it through more randomized controlled trials and conduct long-term protocol studies to further investigate its mechanism of action. Declarations Ethics Approval and Consent to Participate This study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of the Second Affiliated Hospital of Soochow University. (Project No. lc2024009; Ethics approval code: jd-lc2024009-ir01) Written informed consent was obtained from all participants prior to enrollment. Human Ethics and Consent to Participate The ethical approval and informed consent procedures for this study involving human participants are described above. The study was reviewed and approved by the Ethics Committee of the Second Affiliated Hospital of Soochow University, and written informed consent was obtained from all participants. Funding This study was supported by the Suzhou Municipal Health and Family Planning Commission(Grant No. GSWS2022033). Acknowledgments The authors sincerely acknowledge the nursing staff of the outpatient clinic for their assistance in patient reception and questionnaire collection, and our colleagues for their contributions during data collection and analysis. Competing Interests The authors declare that they have no competing interests. Consent for publication : Not applicable. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. References Savarino E, Zingone F, Barberio B, et al. Functional bowel disorders with diarrhoea: Clinical guidelines of the united european gastroenterology and european society for neurogastroenterology and motility[J]. United Eur Gastroenterol J. 2022;10(6):556–84. Sperber AD, Bangdiwala SI, Drossman DA, et al. Worldwide prevalence and burden of functional gastrointestinal disorders, results of rome foundation global study[J]. Gastroenterology. 2021;160(1):99–e1143. 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Clinical efficacy of Mecobalamin Enteric-Coated Tablets combinedwith Trimebutine Maleate Tablets in the treatment of functional diarrhea [J]. Chin J Clin Med. 2017;24(5):782–4. Li Xiaotong K, Nan L, Jiali K, Weizhi C, Zhiqun. Research progress on the relationship between intestinal flora and traditional Chinese medicine in functional diarrhea [J]. J Liaoning Univ Traditional Chin Med. 2023;25(12):60–5. Dai Deru. Observation on the efficacy of Enterogermina combined with Ecologic in the treatment of functional diarrhea with intestinal flora imbalance [EB/OL]. [2024-09-15]. Lembo A, Rao SSC, Heimanson Z, Pimentel M. Abdominal pain response to rifaximin in patients with irritable bowel syndrome with diarrhea[J]. Clin Translational Gastroenterol. 2020;11(3):e00144. Sharara AI, Aoun E, Abdul-Baki H, Mounzer R, Sidani S, Elhajj I. A randomized double-blind placebo-controlled trial of rifaximin in patients with abdominal bloating and flatulence[J]. Am J Gastroenterol. 2006;101(2):326–33. Schoenfeld P, Pimentel M, Chang L, et al. Safety and tolerability of rifaximin for the treatment of irritable bowel syndrome without constipation: A pooled analysis of randomised, double-blind, placebo-controlled trials[J]. Volume 39. Alimentary Pharmacology & Therapeutics; 2014. pp. 1161–8. 10. Lembo A, Pimentel M, Rao SS, et al. Repeat treatment with rifaximin is safe and effective in patients with diarrhea-predominant irritable bowel syndrome[J]. Gastroenterology. 2016;151(6):1113–21. Pimentel M, Lembo A, Chey WD, et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation[J]. N Engl J Med. 2011;364(1):22–32. Lewis SJ, Heaton KW. Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol. 1997;32(9):920–4. Garsed K, Chernova J, Hastings M, et al. A randomized trial of ondansetron for the treatment of irritable bowel syndrome with diarrhoea. Gut. 2014;63(10):1617–25. Singh P, Lee H-N, Rangan V, et al. Similarities in clinical and psychosocial characteristics of functional diarrhea and irritable bowel syndrome with diarrhea[J]. Clin Gastroenterol Hepatology: Official Clin Pract J Am Gastroenterological Association. 2020;18(2):399–e4051. Zhao Y-F, Guo X-J, Zhang Z-S, et al. Epidemiology of functional diarrhea and comparison with diarrhea-predominant irritable bowel syndrome: A population-based survey in China[J]. PLoS ONE. 2012;7(8):e43749. Zhao K. Comparative Study Between RomeⅢand RomeⅣCriteria in College Students With Functional Gastrointestinal Disorders[J]. Chin J Gastroenterol, 2022(6): 336–40. Zhan K, Zheng H, Li J et al. Gut microbiota-bile acid crosstalk in diarrhea-irritable bowel syndrome[J]. BioMed Research International, 2020, 2020: 3828249. Frissora CL, Schiller LR. Getting the BS out of irritable bowel syndrome with diarrhea (IBS-D): Let’s make a diagnosis[J]. Curr Gastroenterol Rep. 2024;26(1):20–9. Pimentel M, Lembo A. Microbiome and its role in irritable bowel syndrome[J]. Dig Dis Sci. 2020;65(3):829–39. Tap J, Derrien M, Törnblom H, et al. Identification of an Intestinal Microbiota Signature Associated With Severity of Irritable Bowel Syndrome[J]. Gastroenterology. 2017;152(1):111–e1238. Carroll IM, Ringel-Kulka T, Siddle JP, Ringel Y. Alterations in composition and diversity of the intestinal microbiota in patients with diarrhea-predominant irritable bowel syndrome[J]. Neurogastroenterol Motil. 2012;24(6):521–30. e248. Saffouri GB, Shields-Cutler RR, Chen J et al. Small intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders[J]. Nature Communications, 2019, 10(1): 2012. Yan F, Polk DB. Probiotics as functional food in the treatment of diarrhea[J]. Curr Opin Clin Nutr Metab Care. 2006;9(6):717–21. Wang F, Zhao T, Wang W, Dai Q, Ma X. Meta-analysis of the efficacy of probiotics to treat diarrhea[J]. Medicine. 2022;101(38):e30880. Yang B, Yue Y, Chen Y, et al. Lactobacillus plantarum CCFM1143 alleviates chronic diarrhea via inflammation regulation and gut microbiota modulation: A double-blind, randomized, placebo-controlled study[J]. Front Immunol. 2021;12:746585. Zeng Z, Yue W, Kined C, et al. Bacillus licheniformis reverses the environmental ceftriaxone sodium-induced gut microbial dysbiosis and intestinal inflammation in mice[J]. Ecotoxicol Environ Saf. 2023;257:114890. Schoenfeld P, Pimentel M, Chang L, et al. Safety and tolerability of rifaximin for the treatment of irritable bowel syndrome without constipation: A pooled analysis of randomised, double-blind, placebo-controlled trials[J]. Volume 39. Alimentary Pharmacology & Therapeutics; 2014. pp. 1161–8. 10. Pimentel M, Cash BD, Lembo A, et al. Repeat rifaximin for irritable bowel syndrome: No clinically significant changes in stool microbial antibiotic sensitivity[J]. Dig Dis Sci. 2017;62(9):2455–63. Acosta A, Camilleri M, Shin A, et al. Effects of rifaximin on transit, permeability, fecal microbiome, and organic acid excretion in irritable bowel syndrome[J]. Clin Translational Gastroenterol. 2016;7(5):e173. The Effect of Rifaximin on Gut Flora and Staphylococcus Resistance. | Digestive Diseases and Sciences[EB/OL]. [2025-02-18]. https://link.springer.com/article/ 10.1007/s10620-013- 2675–0. Calanni F, Renzulli C, Barbanti M, Viscomi GC. Rifaximin: beyond the traditional antibiotic activity[J]. J Antibiot. 2014;67(9):667–70. Ponziani FR, Scaldaferri F, Petito V, et al. The Role of Antibiotics in Gut Microbiota Modulation: The Eubiotic Effects of Rifaximin[J]. Dig Dis. 2016;34(3):269–78. Pretreatment of Epithelial Cells with Rifaximin Alters. Bacterial Attachment and Internalization Profiles - PMC[EB/OL]. [2025-02-18]. Zeber-Lubecka N, Kulecka M, Ambrozkiewicz F, et al. Limited prolonged effects of rifaximin treatment on irritable bowel syndrome-related differences in the fecal microbiome and metabolome[J]. Gut Microbes. 2016;7(5):397–413. Soldi S, Vasileiadis S, Uggeri F, et al. Modulation of the gut microbiota composition by rifaximin in non-constipated irritable bowel syndrome patients: A molecular approach[J]. Clin Exp Gastroenterol. 2015;8:309–25. Additional Declarations No competing interests reported. Supplementary Files FunctionalDiarrheaPatientSymptomQuestionnaire.pdf Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8650251","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":587883334,"identity":"68bd670e-e799-4182-af94-5685a4283ea5","order_by":0,"name":"Jing Zhou","email":"","orcid":"","institution":"Changshu No. 2 People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jing","middleName":"","lastName":"Zhou","suffix":""},{"id":587883335,"identity":"3f2806b1-dec4-4298-a313-a86d94bc6f58","order_by":1,"name":"Guo-Jian Yin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAuUlEQVRIiWNgGAWjYHCCxIcfeGx4+PkbiNeSbCwhkyYjOeMA8VrYJHhsDtsYNCQQqd7g/IIHEhI553kMGA4wfviYQ4yWGw8SDArO3OYxZ25glpy5jSgtBxISJHtu81g2HGBj5iVWywHef+d4DA4kEKvlfENiAw/PARK0SN5gSGaW4EnmkZxxsJk4v/CdP5P+8wOPnT0/f/PBDx+J0aJwIycBymRsIEI9EMj3Hz9AnMpRMApGwSgYuQAA1c07KVsl5tUAAAAASUVORK5CYII=","orcid":"","institution":"The Fourth Affiliated Hospital of Soochow University","correspondingAuthor":true,"prefix":"","firstName":"Guo-Jian","middleName":"","lastName":"Yin","suffix":""},{"id":587883341,"identity":"78e11597-e0a9-4180-b585-f80655220266","order_by":2,"name":"Yu Xin Liu","email":"","orcid":"","institution":"Second Affiliated Hospital of Soochow University","correspondingAuthor":false,"prefix":"","firstName":"Yu","middleName":"Xin","lastName":"Liu","suffix":""},{"id":587883342,"identity":"c40c6b96-be62-4858-8bf2-c184b9e12bdc","order_by":3,"name":"Feng Jie Ji","email":"","orcid":"","institution":"Suzhou BenQ Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Feng","middleName":"Jie","lastName":"Ji","suffix":""}],"badges":[],"createdAt":"2026-01-20 14:46:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8650251/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8650251/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102238965,"identity":"b50d745b-daa0-4453-8a4b-af72adee513b","added_by":"auto","created_at":"2026-02-09 16:42:50","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":39948,"visible":true,"origin":"","legend":"\u003cp\u003eStatistical analysis of urgency and incompleteness of bowel movement\u003c/p\u003e\n\u003cp\u003e*: P \u0026lt; 0.05, **:P \u0026lt; 0.01, #:P \u0026gt; 0.05. A: exposed group; B: unexposed group ; W\u003csub\u003e0\u003c/sub\u003e: before medication ;W\u003csub\u003e1\u003c/sub\u003e: at the end of treatment; W\u003csub\u003e2\u003c/sub\u003e: 1 month after the end of treatment.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8650251/v1/d708bb29d71df0956df48498.jpg"},{"id":105741586,"identity":"8b60e73d-68c6-4d6d-9092-ced536036f1b","added_by":"auto","created_at":"2026-03-30 13:13:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1207567,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8650251/v1/ad75f246-6d5d-43dd-b3f3-f7a425142fd6.pdf"},{"id":102238967,"identity":"6368c9fc-0143-4d78-a242-9ccb18db65e0","added_by":"auto","created_at":"2026-02-09 16:42:50","extension":"pdf","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":161823,"visible":true,"origin":"","legend":"","description":"","filename":"FunctionalDiarrheaPatientSymptomQuestionnaire.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8650251/v1/e6426471cee913c77fd52002.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Efficacy of Rifaximin Combined with Probiotics in the Treatment of Functional Diarrhea: A Prospective Cohort Study","fulltext":[{"header":"Core Tip","content":"\u003cp\u003eFunctional diarrhea (FDr) lacks effective treatment strategies. This prospective cohort study evaluated rifaximin, a non-absorbable antibiotic targeting intestinal microbiota, combined with probiotics in FDr patients. The regimen significantly improved stool frequency, stool consistency, and flatulence, with sustained benefits one month post-treatment and a reduced recurrence rate compared with probiotics alone. No serious adverse events were observed. These findings suggest that rifaximin plus probiotics is a safe and effective therapeutic option for FDr, offering novel insights into microbiota-targeted management of functional gastrointestinal disorders.\u003c/p\u003e"},{"header":"Background","content":"\u003cp\u003eFunctional diarrhea (FDr) is a common functional gastrointestinal disease characterized by persistent or recurrent loose, pasty, or watery stools, typically lasting for more than six months \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. An internet based survey found that FDr affects about 4.7% of the global population, and the incidence rate in China is slightly higher, 5.6% \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAt present, the treatment intervention of FDr mainly focuses on relieving symptoms and improving quality of life. These intervention measures include adjusting diet and lifestyle, medication treatment for diarrhea (such as loperamide), alternative and complementary therapies (including prebiotics and probiotics), cognitive-behavioral therapy and other psychosocial interventions, as well as traditional Chinese medicine \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. Probiotics demonstrate the ability to regulate gut microbiota balance and enhance intestinal barrier defense \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e, and hinder pathogen growth \u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. Many studies \u003csup\u003e[\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e have confirmed the efficacy of probiotics in improving FDr symptoms, and specific combinations of probiotic strains may provide more benefits \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eRifaximin, a broad-spectrum antibiotic exerting a localized effect on intestinal flora without systemic absorption, has demonstrated its effectiveness in managing gastrointestinal disorders. It can significantly alleviate gastrointestinal symptoms such as diarrhea, abdominal pain, and bloating, reduce the risk of systemic side effects, and contribute to enhancing the quality of life \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. Although rifaximin has been proven safe and effective in various situations \u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e],\u003c/sup\u003e the conclusive evidences supporting its specific use in FDr treatment remains elusive\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe aim of this study is to evaluate the efficacy and safety of the combination of rifaximin and probiotics in the treatment of FDr. Patients receiving combined treatment with live Bacillus licheniformis and Lactobacillus acidophilus were assigned to the unexposed group, while patients receiving treatment plus with rifaximin formed the exposed group.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Setting\u003c/h2\u003e \u003cp\u003eThis was a non-randomized, prospective cohort study conducted at the Gastroenterology outpatient department of the Second Affiliated Hospital of Soochow University (Suzhou, China) from April 2022 to February 2024. Patients were provided the option to choose between receiving rifaximin combined with probiotics (exposed group) or probiotics alone (unexposed group) after being informed about the potential benefits and risks of both treatments by the attending physician. The decision was based on patient preference and informed consent.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eParticipants\u003c/h3\u003e\n\u003cp\u003eAdults aged 18\u0026ndash;65 years with a diagnosis of functional diarrhea (FDr) according to the Rome IV criteria were eligible for inclusion. Patients were excluded if they had evidence of organic bowel disease (e.g., inflammatory bowel disease, colon cancer, ischemic bowel disease), severe organ failure (cardiac, renal, hepatic), advanced malignancy, or any conditions that could interfere with their ability to understand or comply with the study protocol, such as severe mental illness or cognitive impairments.\u003c/p\u003e \u003cp\u003e \u003cb\u003eInclusion Criteria\u003c/b\u003e \u003c/p\u003e \u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eAge between 18 and 65 years;\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eDiagnosed with FDr according to Rome IV criteria;\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e Ability to understand the research details and voluntarily sign informed consent;\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eNo FDr-related medication within two weeks prior to enrollment.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e \u003cp\u003e \u003cb\u003eExclusion Criteria\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eColonoscopy indicating inflammatory bowel disease, colon cancer, ischemic bowel disease, or other organic bowel diseases;\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eSevere cardiovascular, renal, hepatic, or other critical organ failure;\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eAdvanced malignancy or severe cachexia;\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePregnancy or breastfeeding status;\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eAllergy to rifaximin or any components of the probiotics used;\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eSevere mental illness or cognitive impairments preventing understanding of or compliance with the study protocol;\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eHistory of alcohol or substance abuse.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e\n\u003ch3\u003eEthics Statement\u003c/h3\u003e\n\u003cp\u003e The study was approved by the Ethics Committee of the Second Affiliated Hospital of Soochow University (Approval No. LC2024009). All participants provided written informed consent before enrollment. The study was conducted in accordance with the 2013 revision of the Declaration of Helsinki.\u003c/p\u003e\n\u003ch3\u003eIntervention\u003c/h3\u003e\n\u003cp\u003ePatients in the exposed group received rifaximin (400 mg twice daily for 6 consecutive days), Bacillus licheniformis (0.25g three times daily for 12 days), and Lactobacillus acidophilus (0.5g three times daily for 12 days). Patients in the unexposed group received the same probiotic regimen without rifaximin. The medications used in the study were:\u003c/p\u003e \u003cp\u003e \u003cb\u003eRifaximin\u003c/b\u003e: Brand name: 'Xifushen', 0.2g tablets (12 tablets per box), manufactured by Alfa Sigma Co., Ltd., approval number H20181212, valid for 36 months, stored in a light-protected, tightly sealed container.\u003c/p\u003e \u003cp\u003e \u003cb\u003eBacillus licheniformis\u003c/b\u003e: Brand name: 'Zhengchangsheng', 0.25g capsules (36 capsules per bottle), manufactured by Northeast Pharmaceutical Group Shenyang No.1 Pharmaceutical Co., Ltd., approval number National Medicine Zhunzi S20073008, valid for 24 months, stored at room temperature in a light-protected, dry place.\u003c/p\u003e \u003cp\u003e \u003cb\u003eLactobacillus acidophilus\u003c/b\u003e: Brand name: 'Yijinkang', 0.5g tablets (24 tablets per box), manufactured by Tonghua Jinma Pharmaceutical Group Co., Ltd., approval number National Medicine Zhunzi H10940114, valid for 24 months, stored in a light-protected, sealed container at room temperature.\u003c/p\u003e\n\u003ch3\u003eEfficacy Endpoints\u003c/h3\u003e\n\u003cp\u003eAs no clinical trials have specifically evaluated rifaximin in functional diarrhea to date, the efficacy endpoints in this study were selected by referring to outcome measures widely adopted in rifaximin clinical trials for diarrhea-predominant irritable bowel syndrome \u003csup\u003e[\u003cspan additionalcitationids=\"CR15 CR16\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePrimary Endpoint\u003c/h2\u003e \u003cp\u003eThe primary efficacy endpoint was the change from baseline (CFB) in the mean number of bowel movements per day (BMD) at the end of treatment (Day 12\u0026thinsp;\u0026plusmn;\u0026thinsp;1) and one month post-treatment (Day 30\u0026thinsp;\u0026plusmn;\u0026thinsp;5). BMD was calculated as the average number of bowel movements recorded over three consecutive days.\u003c/p\u003e \u003cp\u003e \u003cb\u003eSecondary Endpoints\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eChange from baseline in stool consistency assessed by the Bristol Stool Form Scale (BSFS)\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e (types 1\u0026ndash;7) at the end of treatment and one month after treatment;\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eChange from baseline in urgency of defecation and incomplete evacuation, classified into five severity grades: grade 0 (not at all), grade 1 (mildly), grade 2 (moderately), grade 3 (greatly), and grade 4 (extremely);\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePresence or absence of frequent flatulence, borborygmi, mucus in stool, and frothy stool (recorded as yes/no);\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eOverall efficacy, categorized as cured, markedly effective, effective, or ineffective, based on symptom improvement (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEvaluation Criteria for the Overall Therapeutic Effect of Rifaximin\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEffect\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEvaluation Criteria\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCure\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u0026ndash;2 bowel movements daily, well-formed stool, and most symptoms resolved.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMarked Effect\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFewer than 3 bowel movements daily, nearly formed stool unaffected by external factors, with significant symptom improvement.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEffective\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReduced frequency of bowel movements, nearly formed but may vary due to external factors, some symptom improvement.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIneffective\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo notable change in the frequency or consistency of bowel movements; possible worsening and no significant symptom improvement.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eFollow-up and Data Collection\u003c/h3\u003e\n\u003cp\u003eFollow-up assessments were conducted at the end of treatment (Day 12\u0026thinsp;\u0026plusmn;\u0026thinsp;1) and one month after treatment (Day 30\u0026thinsp;\u0026plusmn;\u0026thinsp;5) through clinical surveys, telephone calls, or online questionnaires. Stool hardness was documented via photographs provided by the patients, using a reference image for consistency. Healthcare providers verified the photographs during follow-up visits. Detailed records of any adverse events were promptly documented and managed.\u003c/p\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eData were analyzed using IBM SPSS Statistics version 27.0 (IBM Corp., Armonk, NY). For continuous data, normality was assessed using the Shapiro\u0026ndash;Wilk test. Normally distributed data were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation and analyzed using t-tests. Non-normally distributed data were presented as medians (interquartile ranges) and analyzed using nonparametric tests (Mann-Whitney U test). Categorical data were described using frequencies and percentages and analyzed using chi-square or Fisher\u0026rsquo;s exact test. Repeated measures data were evaluated using ANOVA or the generalized estimating equation (GEE) approach for correlated outcomes.The significance level was set at α\u0026thinsp;=\u0026thinsp;0.05. For multiple comparisons, a Bonferroni correction was applied to adjust for family-wise error rate. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003ePatient Demographics and Baseline Characteristics\u003c/h2\u003e \u003cp\u003eA total of 133 patients were enrolled in this study: 69 in the exposed group (rifaximin\u0026thinsp;+\u0026thinsp;probiotics) and 64 in the unexposed group (probiotics only). After exclusion (due to poor compliance, temporary work changes, or loss to follow-up), 121 patients (62 in the exposed group and 59 in the unexposed group) completed the study and follow-up.\u003c/p\u003e \u003cp\u003eBaseline demographic and clinical characteristics were similar between the two groups (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The mean age of participants was 43.81\u0026thinsp;\u0026plusmn;\u0026thinsp;8.73 years in the exposed group and 42.36\u0026thinsp;\u0026plusmn;\u0026thinsp;11.60 years in the unexposed group (P\u0026thinsp;=\u0026thinsp;0.44). The majority of participants were male (66.9%). The median disease duration was 5 years in both groups, and there were no significant differences in baseline symptom severity (BMD, stool hardness, urgency, incomplete evacuation, flatulence, borborygmi, mucus in stool, and frothy stool) between the two groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics of participants, by group.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eExposed Group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;62)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUnexposed group(n\u0026thinsp;=\u0026thinsp;59)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex, n (%)\u003c/p\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42(67.74%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39(66.10%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.848\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20(32.26%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20(33.90%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge,y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43.81\u0026thinsp;\u0026plusmn;\u0026thinsp;8.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42.36\u0026thinsp;\u0026plusmn;\u0026thinsp;11.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.44\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeight, cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e170.05\u0026thinsp;\u0026plusmn;\u0026thinsp;5.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e169.12\u0026thinsp;\u0026plusmn;\u0026thinsp;9.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.528\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eweight, kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71.36\u0026thinsp;\u0026plusmn;\u0026thinsp;9.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70.58\u0026thinsp;\u0026plusmn;\u0026thinsp;14.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.734\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.338\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThin BMI\u0026lt;18.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(1.69%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNormal 18.5\u0026thinsp;\u0026le;\u0026thinsp;BMI\u0026lt;24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22(35.48%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24(40.68%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOverweight 24\u0026thinsp;\u0026le;\u0026thinsp;BMI\u0026thinsp;\u0026lt;\u0026thinsp;28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31(50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28(16.94%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eObese BMI\u0026gt;28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9(14.52%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(10.17%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisease duration, y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(2\u0026thinsp;~\u0026thinsp;10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(2\u0026thinsp;~\u0026thinsp;10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.68\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11(17.74%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15(25.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.304\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(3.23%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(5.08%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.674\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10(16.13%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11(18.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.715\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlcohol consumption, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10(16.13%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13(22.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.408\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCholecystectomy, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(6.45%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(5.08%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMain Symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.25(2, 3.125)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.5(2, 3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.167\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecondary symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStool hardness score, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.979\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44(71.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42(71.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18(29.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17(28.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrgency of defecation score, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.502\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16(25.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16(27.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9(14.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(11.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21(33.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15(25.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13(21.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15(25.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(4.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(10.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIncomplete evacuation score, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.701\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22(35.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22(37.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14(22.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8(13.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16(25.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17(28.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9(14.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12(20.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(1.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFrequent flatulence, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.336\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43(69.35%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36(61.02%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19(30.65%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23(38.98%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBorborygmi, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.682\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24(38.71%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25(42.37%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38(61.29%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34(57.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMucus in stool, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.563\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19(30.65%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21(35.59%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43(69.35%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38(64.41%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFrothy stool, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.436\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15(24.19%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18(30.51%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47(75.81%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41(69.49%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003ePrimary Endpoint: Bowel Movements per Day (BMD)\u003c/h2\u003e \u003cp\u003eThe mean BMD significantly decreased from baseline in both groups at the end of treatment and one month after treatment (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMean number of bowel movements per day (BMD) and stool characterization statistics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"11\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eW\u003csub\u003e0\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eW\u003csub\u003e1\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eW\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eComparison within\u003c/p\u003e \u003cp\u003eexposed group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eComparison within\u003c/p\u003e \u003cp\u003eunexposed group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003eComparison between groups\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMean Difference\u003c/p\u003e \u003cp\u003e(95% confidence interval)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMean Difference\u003c/p\u003e \u003cp\u003e(95% confidence interval)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eMean Difference\u003c/p\u003e \u003cp\u003e(95% confidence interval)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eBMD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eExposed group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.25\u003c/p\u003e \u003cp\u003e(2, 3.125)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.5\u003c/p\u003e \u003cp\u003e(1, 2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.5\u003c/p\u003e \u003cp\u003e(1, 2.125)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-1.073\u003c/p\u003e \u003cp\u003e(-1.261, -0.884)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e1\u003c/sup\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-0.958\u003c/p\u003e \u003cp\u003e(-1.236, -0.679)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e3\u003c/sup\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-0.368\u003c/p\u003e \u003cp\u003e(-0.627, -0.109)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e5\u003c/sup\u003e=0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnexposed group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003cp\u003e(2, 3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(1.5, 2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003cp\u003e(1.5, 3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-0.887\u003c/p\u003e \u003cp\u003e(-1.101, -0.673)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-0.568\u003c/p\u003e \u003cp\u003e(-0810, -0.325)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e4\u003c/sup\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-0.572\u003c/p\u003e \u003cp\u003e(-0.885, -0.259)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e6\u003c/sup\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eStool hardness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eExposed group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(6, 6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e(4, 5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e(4, 6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-1.855\u003c/p\u003e \u003cp\u003e(-2.154, -1.555)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e1\u003c/sup\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-1.559\u003c/p\u003e \u003cp\u003e(-1.930, -1.189)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e3\u003c/sup\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-0.388\u003c/p\u003e \u003cp\u003e(-0.848, 0.068)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e5\u003c/sup\u003e=0.096\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnexposed group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(6, 7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e(4, 6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(5, 6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-1.661\u003c/p\u003e \u003cp\u003e(-1.993, -1.330)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-1.153\u003c/p\u003e \u003cp\u003e(-1.537, -0.768)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e4\u003c/sup\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-0.602\u003c/p\u003e \u003cp\u003e(-1.088, -0.115)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e6\u003c/sup\u003e=0.015\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"11\"\u003eW\u003csub\u003e0\u003c/sub\u003e: before medication; W\u003csub\u003e1\u003c/sub\u003e: at the end of treatment; W\u003csub\u003e2\u003c/sub\u003e: 1 month after the end of treatment. \u003cem\u003eP\u003c/em\u003e\u003csup\u003e1\u003c/sup\u003e is the within-group comparison of the exposed group at the end of treatment, \u003cem\u003eP\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e is the within-group comparison of the exposed group at 1 month after the end of treatment, \u003cem\u003eP\u003c/em\u003e\u003csup\u003e3\u003c/sup\u003e is the within-group comparison of the unexposed group at the end of treatment, \u003cem\u003eP\u003c/em\u003e\u003csup\u003e4\u003c/sup\u003e is the within-group comparison of the unexposed group at 1 month after the end of treatment. \u003cem\u003eP\u003c/em\u003e\u003csup\u003e5\u003c/sup\u003e is the between-group comparison of the exposed group and the unexposed group at the end of treatment. \u003cem\u003eP\u003c/em\u003e\u003csup\u003e6\u003c/sup\u003e is a between-group comparison between the exposed group and the unexposed group 1 month after the end of drug\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn the exposed group, BMD decreased from 2.25 (2.00, 3.125) at baseline to 1.5 (1.00, 2.00) at the end of treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and to 1.5 (1.00, 2.125) at one month post-treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eIn the unexposed group, BMD decreased from 2.5 (2.00, 3.50) at baseline to 2.0 (1.50, 2.50) at the end of treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and to 2.5 (1.50, 3.00) at one month post-treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eBetween-group comparison at the end of treatment revealed a greater reduction in BMD in the exposed group (mean difference: \u0026minus;0.368, P\u0026thinsp;=\u0026thinsp;0.005), with a more significant improvement one month after treatment (mean difference: \u0026minus;0.572, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eSecondary Endpoint 1: Stool Hardness\u003c/h2\u003e \u003cp\u003eBoth groups showed significant improvement in stool hardness from baseline at the end of treatment and one month after treatment (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn the exposed group, stool hardness decreased from 6 (6.00, 6.00) at baseline to 4 (4.00, 5.00) at the end of treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and to 4 (4.00, 6.00) one month post-treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eIn the unexposed group, stool hardness decreased from 6 (6.00, 7.00) at baseline to 5 (4.00, 6.00) at the end of treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and to 6 (5.00, 6.00) at one month post-treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eHowever, there was no significant difference in stool hardness between the two groups at the end of treatment (P\u0026thinsp;=\u0026thinsp;0.096), though a significant difference was observed one month after treatment (mean difference: \u0026minus;0.602, P\u0026thinsp;=\u0026thinsp;0.015).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eSecondary Endpoint 2: Gastrointestinal Symptoms\u003c/h2\u003e \u003cdiv id=\"Sec16\" class=\"Section3\"\u003e \u003ch2\u003eUrgency of Defecation and Incomplete Evacuation\u003c/h2\u003e \u003cp\u003eBoth groups experienced improvements in urgency of defecation and incomplete evacuation at the end of treatment and one month post-treatment (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). However, no significant difference was observed between the two groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05 for both time points), indicating that rifaximin had a limited effect on these symptoms.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eFlatulence, Borborygmi, Mucus in Stool, and Frothy Stool\u003c/h2\u003e \u003cp\u003eThere were significant differences between the groups in terms of flatulence and borborygmi, but no significant differences for mucus in stool and frothy stool (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eStatistical analysis of the efficacy of other symptoms\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eW\u003csub\u003e0\u003c/sub\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eW\u003csub\u003e1\u003c/sub\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eW\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eWithin Group Comparison\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eBetween Group Comparison\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eRR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eFrequent flatulence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eExposed group(n\u0026thinsp;=\u0026thinsp;62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYES\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e43(69.35%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e10(6.13%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e15(24.19%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e1\u003c/sup\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e5\u003c/sup\u003e=0.026\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19(30.65%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e52(83.87%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e47(75.81%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eUnexposed group(n\u0026thinsp;=\u0026thinsp;59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYES\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e36(61.02%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e20(33.90%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e27(45.76%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e3\u003c/sup\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e6\u003c/sup\u003e=0.008\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e23(38.98%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e39(66.10%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e32(54.24%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e4\u003c/sup\u003e=0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eBorborygmi\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eExposed group(n\u0026thinsp;=\u0026thinsp;62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYES\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e24(38.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8(12.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e13(20.97%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e1\u003c/sup\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e5\u003c/sup\u003e=0.533\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e38(61.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e54(87.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e49(79.03%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e=0.015\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eUnexposed group(n\u0026thinsp;=\u0026thinsp;59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYES\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e25(42.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e10(16.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e18(30.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e3\u003c/sup\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e6\u003c/sup\u003e=0.232\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e34(57.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e49(83.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e41(69.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e4\u003c/sup\u003e=0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eMucus in stool\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eExposed group(n\u0026thinsp;=\u0026thinsp;62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYES\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19(30.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9(14.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e10(16.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e1\u003c/sup\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e5\u003c/sup\u003e=0.909\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e43(69.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e53(85.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e52(83.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e=0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eUnexposed group(n\u0026thinsp;=\u0026thinsp;59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYES\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e21(35.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9(15.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e14(23.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e3\u003c/sup\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e6\u003c/sup\u003e=0.297\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e38(64.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e50(84.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e45(76.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e4\u003c/sup\u003e=0.016\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eFrothy stool\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eExposed group(n\u0026thinsp;=\u0026thinsp;62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYES\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15(24.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7(11.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8(12.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e1\u003c/sup\u003e=0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e5\u003c/sup\u003e=0.705\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e47(75.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e55(88.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e54(87.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e=0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eUnexposed group(n\u0026thinsp;=\u0026thinsp;59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYES\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18(30.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8(13.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e11(18.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e3\u003c/sup\u003e=0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e6\u003c/sup\u003e=0.388\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e41(69.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e51(86.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e48(81.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e4\u003c/sup\u003e=0.016\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eW\u003csub\u003e1\u003c/sub\u003e: at the end of treatment; W\u003csub\u003e2\u003c/sub\u003e: 1 month after the end of treatment. \u003cem\u003eP\u003c/em\u003e\u003csup\u003e1\u003c/sup\u003e is the within-group comparison of the exposed group at the end of treatment, \u003cem\u003eP\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e is the within-group comparison of the exposed group at 1 month after the end of treatment, \u003cem\u003eP\u003c/em\u003e\u003csup\u003e3\u003c/sup\u003e is the within-group comparison of the unexposed group at the end of treatment, \u003cem\u003eP\u003c/em\u003e\u003csup\u003e4\u003c/sup\u003e is the within-group comparison of the unexposed group at 1 month after the end of treatment. \u003cem\u003eP\u003c/em\u003e\u003csup\u003e5\u003c/sup\u003e is the between-group comparison of the exposed group and the unexposed group at the end of treatment. \u003cem\u003eP\u003c/em\u003e\u003csup\u003e6\u003c/sup\u003e is a between-group comparison between the exposed group and the unexposed group 1 month after the end of drug.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eFlatulence\u003c/b\u003e: In the exposed group, the relative risk (RR) at the end of treatment was 0.23 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and 0.35 after one month of treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In the unexposed group, the RR at the end of treatment was 0.56 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and 0.75 one month post-treatment (P\u0026thinsp;=\u0026thinsp;0.004). The between-group comparison showed a statistically significant difference at both time points (end of treatment: P\u0026thinsp;=\u0026thinsp;0.026; one month post-treatment: P\u0026thinsp;=\u0026thinsp;0.008).\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eBorborygmi\u003c/strong\u003e \u003cp\u003eIn the exposed group, the RR was 0.33 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) at the end of treatment and 0.54 (P\u0026thinsp;=\u0026thinsp;0.015) one month post-treatment. In the unexposed group, the RR was 0.40 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) at the end of treatment and 0.72 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) one month post-treatment. No significant difference was observed between the groups at either time point (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eMucus in Stool\u003c/strong\u003e \u003cp\u003eIn the exposed group, RR was 0.47 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) at the end of treatment and 0.53 (P\u0026thinsp;=\u0026thinsp;0.005) one month post-treatment. In the unexposed group, RR was 0.43 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) at the end of treatment and 0.67 (P\u0026thinsp;=\u0026thinsp;0.016) one month post-treatment. There was no significant difference between the two groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eFrothy Stool\u003c/strong\u003e \u003cp\u003eThe exposed group showed an RR of 0.47 (P\u0026thinsp;=\u0026thinsp;0.003) at the end of treatment and 0.53 (P\u0026thinsp;=\u0026thinsp;0.006) one month post-treatment. In the unexposed group, RR was 0.44 (P\u0026thinsp;=\u0026thinsp;0.003) at the end of treatment and 0.61 (P\u0026thinsp;=\u0026thinsp;0.016) one month post-treatment. Again, there was no significant difference between the two groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eOverall Efficacy\u003c/h2\u003e \u003cp\u003eAt the end of treatment, the overall response rate (cured, markedly effective, and effective) was significantly higher in the exposed group compared to the unexposed group (87.1% vs. 72.9%, P\u0026thinsp;=\u0026thinsp;0.021). This trend continued one month post-treatment, with the exposed group showing a greater improvement (77.4% vs. 54.2%, P\u0026thinsp;=\u0026thinsp;0.003) (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eStatistical assessment of efficacy at the end of treatment and at 1 month after the end of treatment\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCure\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMarked Effect\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eEffective\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIneffective\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOverall effective rate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eW\u003csub\u003e1\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eExposed group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10(16.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e31(50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e13(21.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e8(12.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e87.10%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnexposed group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12(20.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e14(23.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e17(28.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e16(27.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e72.90%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eW\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eExposed group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11(17.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e23(37.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e14(22.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e14(22.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e77.40%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnexposed group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9(15.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7(11.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e16(27.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e27(45.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e54.20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eOverall effective rate = (cured\u0026thinsp;+\u0026thinsp;apparent\u0026thinsp;+\u0026thinsp;effective)/total. A: exposed group; B: unexposed group ;W1: at the end of treatment; W\u003csub\u003e2\u003c/sub\u003e: 1 month after the end of treatment.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eSafety\u003c/h2\u003e \u003cp\u003eNo serious adverse events were reported during the study. Both treatment regimens were well tolerated, and there were no significant differences in adverse events between the two groups.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe findings of this study suggested that the combination of rifaximin and probiotics for a 12 day course was a safe and effective treatment option for FDr patients, according to the definition of Rome IV criteria. The observed improvement in gastrointestinal (GI) symptoms indicated that rifaximin might serve as a feasible therapeutic approach for FDr, with its benefits lasting for one month after the end of treatment.\u003c/p\u003e \u003cp\u003eThe Rome IV diagnostic criteria distinguish FDr from irritable bowel syndrome with diarrhoea (IBS-D) primarily by the absence of recurrent abdominal pain in FDr, focusing primarily on chronic diarrhoea. Both of these diseases are classified as functional gastrointestinal disorders, with similar physiological and psychological manifestations. According to Prashant Singh\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e et al., although the frequency of diarrhea is comparable, IBS-D patients experience a higher proportion and severity of abdominal pain compared to those with FDr. In addition, the incidence of anxiety, depression, and sleep disorders is similar in these two situations. Yan-Fang Zhao\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e et al. noticed that the fecal characteristics of FDr and IBS-D are similar. However, the characteristics of IBS-D are more frequent bowel movements (\u0026gt;\u0026thinsp;3 times), urgency of bowel movements, and bloating.\u003c/p\u003e \u003cp\u003e Investigations based on the Rome II criteria suggest that some cases initially diagnosed wth IBS-D might actually meet the criteria for FDr under newer guidelines. Studies have shown that there was a significant difference in the incidence rate when using Rome III and Rome IV criteria for diagnosis \u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. Given their similarities, it has been proposed that FDr and IBS-D might represent different stages of the same disease spectrum, ranging from mild/painless chronic diarrhea to painful chronic diarrhea\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003e15%-20% of IBS-D cases are linked to gut microbiota, and dysbiosis can affect motility, immune function, and barrier integrity \u003csup\u003e[\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. Specific gut bacteria are associated with the severity of symptoms\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. I M Carroll\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e et al. found that compared to healthy subjects, IBS-D patients had significantly more abundance of Enterobacteriaceae, while fecal Enterococcus was significantly reduced, and the overall abundance of bacteria was lower. Saffouri GB\u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e et al. reported that FDr is associated with changes in gut microbiota, including small intestinal bacterial overgrowth (SIBO). Chronic diarrhea in both cases may involve multiple pathogenic mechanisms, with dysbiosis of the gut microbiota being a common factor.\u003c/p\u003e \u003cp\u003e The American Gastroenterological Association's 2022 guidelines recommend various treatment options for FDr, including antidiarrhoeal agents, 5-HT3 receptor antagonists, probiotics, and prebiotics. As is well known, probiotics such as lactobacilli and bifidobacteria can protect intestinal epithelial cells, enhance barrier function, and regulate intestinal microbiota\u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. A meta-analysis has shown that probiotics can improve stool frequency, morphology, and related symptoms in patients with diarrhoea\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e. A specific study on Lactobacillus plantarum CCFM1143 demonstrated its ability to alleviate chronic diarrhoea by modulating gut microbiota and reducing inflammation\u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e. Evidence supports using specific probiotic combinations for treatment. Based on guidelines, literature review, and clinical experience, our center selected a combination of Lactobacillus acidophilus complex and Bacillus licheniformis for clinical research.\u003c/p\u003e \u003cp\u003eThis study indicated that the combined use of these two probiotics significantly improved patients' symptoms compared to baseline. This mechanism may involve Bacillus licheniformis restoring gut microbiota balance and reducing inflammation, while Lactobacillus acidophilus contains four types of bacteria that can increase bacterial abundance.\u003c/p\u003e \u003cp\u003eA study showed that Bacillus licheniformis reversed ceftriaxone sodium-induced dysbiosis and intestinal inflammation in mice, promoting beneficial bacteria growth (e.g., fungi and Lactobacillus) \u003csup\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e. Another study demonstrated its ability to repair intestinal barrier damage and restore tight junction protein expression after antibiotic treatment, which is crucial for maintaining intestinal integrity and function.\u003c/p\u003e \u003cp\u003eThe efficacy and safety of rifaximin in the treatment of IBS-D have been confirmed, but its efficacy on FDr is still unclear due to limited clinical research. In two phase 3 randomized double-blind trials with identical designs, compared with the placebo group, the proportion of IBS-D patients who received treatment with rifaximin 550 mg three times a day for 14 days had a higher rate of symptom relief (40.7% vs. 31.7%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01)\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. In another randomized double-blind trial evaluating repeated treatment with the same regimen, the safety of rifaximin was comparable to placebo \u003csup\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOur center has accumulated rich clinical experience in the treatment of FDr over the past period. Before starting the study, we decided on a treatment regimen of rifaximin 400 mg twice daily for 6 consecutive days, considering guideline recommendations, relevant literature, and patient affordability. Patients were fully informed about the differences between the two treatment regimens before starting therapy and have the option to choose whether or not to receive treatment with rifaximin.\u003c/p\u003e \u003cp\u003eThe results of this study indicated that the combination of rifaximin with Lactobacillus acidophilus and Bacillus licheniformis was effective in treating FDr. This combination showed better efficacy than using the probiotics alone, suggesting rifaximin's potential for FDr treatment. Rifaximin can bind to the DNA-dependent RNA polymerase b subunit of target bacteria, inhibiting bacterial RNA synthesis \u003csup\u003e[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/sup\u003e. IBS-D could be treated with rifaximin by regulating the intestinal flora \u003csup\u003e[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/sup\u003e. It can promote the growth of beneficial bacteria such as bifidobacteria and lactobacilli without significantly altering the overall composition of the gut microbiota \u003csup\u003e[\u003cspan additionalcitationids=\"CR35\" citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]\u003c/sup\u003e. Additionally, rifaximin stabilizes epithelial cells and reduces intestinal inflammation \u003csup\u003e[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe mechanism behind rifaximin's effectiveness with probiotics may involve normalizing gut flora, reducing inflammation, and restoring barrier function. However, studies show that rifaximin\u0026rsquo;s effect on flora are limited and short-lived \u003csup\u003e[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]\u003c/sup\u003e. Some patients experienced symptom recurrence after one month of treatment. Our next step will be to investigate the effects of repeated rifaximin treatments for FDr, as well as longer-term follow-up.\u003c/p\u003e \u003cp\u003eLimitations of this study include its single-center design and small sample size, which reduce the reliability of the findings. There was no unexposed group receiving rifaximin alone, and non-randomization was a limited factor. This study did not fully explore the specific mechanisms by which the combination of rifaximin and probiotics may benefit patients diagnosed with FDr..\u003c/p\u003e \u003cp\u003eOverall, the combination of rifaximin and probiotics is safe and effective for short-term treatment of FDr, but it is necessary to validate it through more randomized controlled trials and conduct long-term protocol studies to further investigate its mechanism of action.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Approval and Consent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of the Second Affiliated Hospital of Soochow University.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(Project No. lc2024009; Ethics approval code: jd-lc2024009-ir01)\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from all participants prior to enrollment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHuman Ethics and Consent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe ethical approval and informed consent procedures for this study involving human participants are described above. The study was reviewed and approved by the Ethics Committee of the Second Affiliated Hospital of Soochow University, and written informed consent was obtained from all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the Suzhou Municipal Health and Family Planning Commission(Grant No. GSWS2022033).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors sincerely acknowledge the nursing staff of the outpatient clinic for their assistance in patient reception and questionnaire collection, and our colleagues for their contributions during data collection and analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e: Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSavarino E, Zingone F, Barberio B, et al. 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Neurogastroenterol Motil. 2012;24(6):521\u0026ndash;30. e248.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaffouri GB, Shields-Cutler RR, Chen J et al. Small intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders[J]. Nature Communications, 2019, 10(1): 2012.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYan F, Polk DB. Probiotics as functional food in the treatment of diarrhea[J]. Curr Opin Clin Nutr Metab Care. 2006;9(6):717\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang F, Zhao T, Wang W, Dai Q, Ma X. Meta-analysis of the efficacy of probiotics to treat diarrhea[J]. Medicine. 2022;101(38):e30880.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang B, Yue Y, Chen Y, et al. Lactobacillus plantarum CCFM1143 alleviates chronic diarrhea via inflammation regulation and gut microbiota modulation: A double-blind, randomized, placebo-controlled study[J]. Front Immunol. 2021;12:746585.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZeng Z, Yue W, Kined C, et al. Bacillus licheniformis reverses the environmental ceftriaxone sodium-induced gut microbial dysbiosis and intestinal inflammation in mice[J]. Ecotoxicol Environ Saf. 2023;257:114890.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchoenfeld P, Pimentel M, Chang L, et al. Safety and tolerability of rifaximin for the treatment of irritable bowel syndrome without constipation: A pooled analysis of randomised, double-blind, placebo-controlled trials[J]. Volume 39. Alimentary Pharmacology \u0026amp; Therapeutics; 2014. pp. 1161\u0026ndash;8. 10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePimentel M, Cash BD, Lembo A, et al. Repeat rifaximin for irritable bowel syndrome: No clinically significant changes in stool microbial antibiotic sensitivity[J]. Dig Dis Sci. 2017;62(9):2455\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAcosta A, Camilleri M, Shin A, et al. Effects of rifaximin on transit, permeability, fecal microbiome, and organic acid excretion in irritable bowel syndrome[J]. Clin Translational Gastroenterol. 2016;7(5):e173.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThe Effect of Rifaximin on Gut Flora and Staphylococcus Resistance. | Digestive Diseases and Sciences[EB/OL]. [2025-02-18]. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://link.springer.com/article/\u003c/span\u003e\u003cspan address=\"https://link.springer.com/article/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s10620-013-\u003c/span\u003e\u003cspan address=\"10.1007/s10620-013-\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e 2675\u0026ndash;0.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCalanni F, Renzulli C, Barbanti M, Viscomi GC. Rifaximin: beyond the traditional antibiotic activity[J]. J Antibiot. 2014;67(9):667\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePonziani FR, Scaldaferri F, Petito V, et al. The Role of Antibiotics in Gut Microbiota Modulation: The Eubiotic Effects of Rifaximin[J]. Dig Dis. 2016;34(3):269\u0026ndash;78.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePretreatment of Epithelial Cells with Rifaximin Alters. Bacterial Attachment and Internalization Profiles - PMC[EB/OL]. [2025-02-18].\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZeber-Lubecka N, Kulecka M, Ambrozkiewicz F, et al. Limited prolonged effects of rifaximin treatment on irritable bowel syndrome-related differences in the fecal microbiome and metabolome[J]. Gut Microbes. 2016;7(5):397\u0026ndash;413.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSoldi S, Vasileiadis S, Uggeri F, et al. Modulation of the gut microbiota composition by rifaximin in non-constipated irritable bowel syndrome patients: A molecular approach[J]. Clin Exp Gastroenterol. 2015;8:309\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"chronic diarrhea, functional diarrhea, rifaximin, probiotics, gut microbiota","lastPublishedDoi":"10.21203/rs.3.rs-8650251/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8650251/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eFunctional diarrhea (FDr) is a common functional gastrointestinal disorder characterized by chronic or recurrent loose stools without organic pathology. It has a worldwide prevalence and exerts a substantial negative impact on patients\u0026rsquo; quality of life. Current therapeutic options for FDr remain limited and are often unsatisfactory. Rifaximin is a minimally absorbed, broad-spectrum, gut-targeted antibiotic with modulatory effects on intestinal microbiota and mucosal inflammation. While rifaximin has demonstrated efficacy in irritable bowel syndrome with diarrhea, robust evidence for its therapeutic role in FDr is lacking.\u003c/p\u003e\u003ch2\u003eAims\u003c/h2\u003e \u003cp\u003eThis prospective cohort study aimed to investigate the efficacy and safety of rifaximin combined with probiotics in improving clinical symptoms and reducing recurrence in patients with FDr.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eFrom April 2022 to June 2024, 121 patients diagnosed with FDr at the Department of Gastroenterology, the Second Affiliated Hospital of Soochow University, were consecutively enrolled. Patients chose either rifaximin combined with probiotics (exposed group) or probiotics alone (unexposed group). All patients received probiotics as baseline therapy, while the exposed group additionally received rifaximin. Symptom changes, including mean daily stool frequency, stool consistency, urgency, incomplete evacuation, flatulence, borborygmi, and presence of mucus or foam, were recorded at baseline, at the end of treatment, and one month after treatment. Primary outcomes were improvements in stool frequency and stool consistency. Secondary outcomes included changes in other gastrointestinal symptoms and overall response rate. Statistical analysis was performed using chi-square and paired t-tests, with P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 considered significant.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAt the end of treatment, both groups showed significant improvement compared with baseline across all evaluated symptoms. Between-group comparison demonstrated that the rifaximin group achieved significantly greater improvement in stool frequency and flatulence (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). At one month post-treatment, partial symptom relapse was observed, but both groups maintained better outcomes compared with baseline. The rifaximin group exhibited significantly greater improvement in stool frequency, stool consistency, and flatulence than the control group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The overall response rate was 87.1% versus 72.9% at treatment completion (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) and 77.4% versus 54.2% at one month post-treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). No serious adverse events were reported.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eRifaximin combined with probiotics effectively improves stool frequency, stool consistency, and flatulence in patients with FDr, reduces recurrence, and enhances quality of life. The regimen was well tolerated and may represent a promising therapeutic option for FDr, warranting further validation in randomized controlled trials.\u003c/p\u003e","manuscriptTitle":"Efficacy of Rifaximin Combined with Probiotics in the Treatment of Functional Diarrhea: A Prospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-09 16:42:43","doi":"10.21203/rs.3.rs-8650251/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ec5efdd3-ec42-4103-8007-d033ccb3a362","owner":[],"postedDate":"February 9th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-30T13:12:13+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-09 16:42:43","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8650251","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8650251","identity":"rs-8650251","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}