Chronic intestinal pseudo‑obstruction is associated with small intestinal bacterial overgrowth

Chronic intestinal pseudo‑obstruction is associated with small intestinal bacterial overgrowth | 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 Chronic intestinal pseudo‑obstruction is associated with small intestinal bacterial overgrowth Takanori Igarashi, Kentaro Tominaga, Kunihiko Yokoyama, Takuya Wakabayashi, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6928176/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 Purpose Small intestinal bacterial overgrowth (SIBO) is associated with various gastrointestinal diseases; however, its relationship with chronic intestinal pseudo-obstruction (CIPO) remains unclear. This study aimed to determine the prevalence and characteristics of SIBO in CIPO. Methods Between April 2019 and May 2025, we conducted a cross-sectional and prospective cohort study involving 10 outpatients diagnosed with CIPO at our hospital and 10 healthy controls. SIBO was diagnosed using a glucose-loaded hydrogen/methane breath test according to the North American Consensus criteria. We investigated the prevalence and clinical characteristics of SIBO in patients with CIPO. Results The 10 patients with CIPO comprised four males and six females, with a mean age of 48.1 ± 13.6 years. CIPO characteristics were secondary and primary in seven and three cases, respectively; the affected site was the small and large intestine in seven and three cases, respectively. Five of the 10 patients with CIPO were SIBO-positive, and all of them had the hydrogen-type phenotype; SIBO rate was significantly higher in patients with CIPO than in healthy participants (50% vs. 10%, p < 0.01). In CIPO, hydrogen-type SIBO-positive patients tended to have a lower body mass index and stronger diarrhea symptoms than did hydrogen-type SIBO-negative patients. In one case, metronidazole was effective, and the SIBO test result was negative after treatment. Conclusions This is the first report of methane and hydrogen SIBO in Asian patients with CIPO. Hydrogen-type SIBO is more common than methane-type SIBO in Japanese patients with CIPO. Chronic intestinal pseudo‑obstruction Small intestinal bacterial overgrowth Breath tests Hydrogen Methanogen Metronidazole Figures Figure 1 Figure 2 Figure 3 Introduction Chronic intestinal pseudo-obstruction (CIPO) is a rare clinical syndrome that was first reported by Dudley et al. in 1958 [ 1 ]. CIPO is a functional motility disorder characterized by episodic obstructive symptoms without a mechanical cause. However, its etiology and causes are not well understood. CIPO has been increasingly identified as a cause of chronic malabsorption and intestinal failure [ 2 ]. When impairment of gut motility and transit is severe, small intestinal bacterial overgrowth (SIBO) may occur, further contributing to malnutrition [ 3 ]. Notably, SIBO may exacerbate intestinal dysmotility [ 4 ]. Emerging evidence suggests an association between CIPO and SIBO [ 5 ]. A study conducted in Chile explored this association and found that the prevalence of SIBO (hydrogen type) in 40 patients with CIPO is 60% [ 6 ]. However, at that time, methane was not measured; only hydrogen was measured. Subsequent advancements in our understanding of the gut microbiome and the availability of breath tests for measuring hydrogen and methane have facilitated the study of the physiological effects of these gases on different SIBO phenotypes and their associated clinical symptoms. Due to the contrasting effects of methane and hydrogen on intestinal motility and variable manifestations, excessive methane production has led to the adoption of the term “intestinal methanogen overgrowth” (IMO) [ 7 ]. Nonetheless, there are limited studies on the prevalence of hydrogen and methane-producing bacterial overgrowth subtypes in patients with CIPO [ 8 ]. Additionally, data exploring the demographics and clinical characteristics of patients with CIPO and SIBO are limited. Our previous reports indicate an association between patients with cirrhosis and SIBO [ 9 , 10 ]. This study aimed to identify and compare the prevalence of hydrogen and methane production in patients with CIPO. We present our findings alongside a review of previous studies. Material and methods Subjects and study protocol This cross-sectional and prospective cohort study was conducted at Niigata University. This study was approved by the ethical review board of Niigata University (Approval Number 2019–0226). Patients screened for the study were those admitted or visited due to CIPO between April 2019 and May 2025. Patients (aged 18 years or older) who were diagnosed with CIPO according to all relevant diagnostic criteria proposed by the Japanese Ministry of Health, Labor, and Welfare [ 11 ], including documented pathological bowel dilatation in the absence of mechanical obstruction on imaging, were recruited. CIPO is classified as either primary (no underlying cause identified) or secondary (known cause determined, such as systemic sclerosis or drug-induced). Overall, 10 patients were included in this study. All patients agreed to participate in the study and provided written informed consent. Moreover, 10 healthy controls with no symptoms and no history of underlying diseases or surgery wishing to undergo SIBO testing participated. The authors ensure that this study is conducted in accordance with the principles of the Declaration of Helsinki and with ethical guidelines for medical and biological research involving human subjects in Japan. Diagnosis of SIBO In this study, a breath test was performed to diagnose SIBO. For accurate diagnosis, bread, pasta, and noodles, which increase hydrogen production, were not allowed for 24 h prior to the breath test. In addition, oral intake of water or tea was not allowed for 12 h prior to the test. Regular medications were administered 2 h before the test, if necessary, and participants were advised to avoid drinking, exercising, and smoking during this period. Oral rinsing was performed to avoid the metabolism of sugar substrates by oral bacteria. Breath measurements (hydrogen and methane concentrations) were performed three times before sugar substrate loading, and the average score was used as the baseline. Subsequently, breath measurements were performed every 15 min after loading and up to 120 or 180 min. The sugar substrate used was 50 g of glucose. Exhaled hydrogen and methane concentrations were measured using a BGA2000D instrument (Laboratory for Expiration Biochemistry Nourishment Metabolism Co., Ltd., Nara, Japan) (Fig. 1 a, b). According to the North American consensus [ 12 , 13 ], the following two diagnostic criteria for SIBO were used: a rise of ≥ 20 ppm from baseline in hydrogen by 90 min and a level of ≥ 10 ppm in methane. We have previously used these criteria to report the association between patients with cirrhosis and SIBO [ 9 , 10 , 14 ]. ΔH 2 in Table 1 refers to the increase in hydrogen concentration from the baseline, and the CH 4 peak value represents the highest methane concentration. Furthermore, cases with elevated hydrogen levels were defined as H-SIBOs, while those with elevated methane levels were defined as M-SIBOs, as previously reported [ 15 ]. M-SIBO is synonymous with IMO. In this study, both hydrogen- and methane-positive cases were included in the positive group for each sub-analysis. Statistical analysis Continuous and categorical variables are expressed as mean ± SE and number (%), respectively. Pearson's chi-square test and Mann–Whitney U test were used for statistical analyses with the SPSS statistical package (version 24.0; IBM SPSS Japan Inc., Tokyo, Japan). Statistical significance was set at P < 0.05. Results The study included 10 patients with CIPO, comprising four males and six females, with a mean age of 48.1 ± 13.6 years and a mean duration of illness of 32.7 ± 35.5 months. The mean body mass index (BMI) of patients with CIPO was 16.9 ± 2.5 kg/m², and eight out of 10 were underweight (BMI < 18.5), according to the Japan Society for the Study of Obesity (Table 1). Conversely, the mean age and BMI of the healthy controls were 31.6 ± 4.2 years and 22.6 ± 2.5 kg/m², respectively. The characteristics of CIPO were secondary in seven cases and primary in three cases. The underlying diseases associated with secondary CIPO included systemic sclerosis (one case), familial Mediterranean fever (one case), polymyositis (one case), Hashimoto disease (one case), pregnancy (two cases), and schizophrenia (drug-induced) (one case). The affected site was the small intestine in seven cases and the large intestine in three cases. Abdominal radiographs, computed tomography, cine-magnetic resonance imaging (MRI), and breath test results for a representative case of CIPO are shown in Fig. 2 . This is a case of secondary intestinal pseudo-obstruction that developed in a 31-year-old woman after pregnancy and childbirth (Case No. 5). The symptoms included abdominal pain, bloating, and diarrhea. Abdominal radiography revealed significant gaseous distension, predominantly in the small intestine. Abdominal radiographs and computed tomography demonstrated markedly dilated intestinal loops with air-fluid levels (Fig, 2a, b). Cine-MRI revealed small bowel dilatation and reduced peristalsis (Fig. 2 c). A breath test confirmed the diagnosis of hydrogen-type SIBO, according to the North American Consensus (Fig. 2 d). In our study, as a result of hydrogen/methane breath tests, five out of 10 cases were SIBO-positive using the North American Consensus (six out of 10 using the Rome Consensus [ 16 ]), and all cases were associated with SIBO-phenotype hydrogen type. Excluding two cases of colonic CIPO (cases no. 7 and 10) undergoing postoperative follow-up, five of eight cases (62.5%) of untreated CIPO were positive for hydrogen-type SIBO. In contrast, when SIBO was measured in 10 healthy controls (male to female ratio 8:2, average age 31.6 ± 4.22 years, average BMI 22.7 ± 2.46, no symptoms, no history of underlying diseases or surgery), only one case was diagnosed as having methane SIBO, and no participant was diagnosed with hydrogen SIBO. The rate of SIBO was significantly higher in the CIPO group than in the healthy control group (50% vs. 10%, p < 0.01) (Fig, 3a). Among patients with CIPO, SIBO-positive individuals tended to have a lower BMI than did SIBO-negative participants (SIBO-positive vs. SIBO-negative; 15.6 kg/m 2 vs. 18.0 kg/m 2 ), with no difference in age or sex. The symptoms observed included abdominal pain, abdominal fullness, nausea, diarrhea, and constipation. SIBO-positive patients were relatively more likely to complain of abdominal pain and nausea than SIBO-negative patients. Furthermore, while no H-SIBO-negative patients experienced diarrhea, this symptom was observed in two out of five H-SIBO-positive patients. Patients who tested positive for hydrogen-type SIBO had a higher rate (40%) of diarrhea symptoms than did those who tested negative. Of the five SIBO-positive patients, case 2 underwent colostomy, and cases 1 and 5 were treated with metronidazole, which improved their symptoms (Fig, 3b). After treatment, SIBO was measured, and two (Case 1 and Case 2) out of the three patients tested negative. Cases 3 and 4 were treated with a low Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols (FODMAP) diet; however, SIBO testing was not performed after treatment due to patient preference. Discussion To date, limited reports have been published on the relationship between CIPO and SIBO (Table 2). In 2014, Pérez et al. first reported the incidence of SIBO in patients with CIPO [ 6 ]. Using breath hydrogen concentration measurements from the lactulose hydrogen breath test (LBT), SIBO was detected in 60% of 40 patients with CIPO. However, at that time, methane was not measured; only hydrogen was recorded, and SIBO using the LBT was defined as an increase of > 20 ppm in two or more figures in the first 60 min. In 2017, Lili et al. measured hydrogen gas in the breath of patients with CIPO using the LBT and verified it using the Rome Consensus [ 17 ]. SIBO was diagnosed if breath concentrations of hydrogen or methane were ≥ 12 ppm over baseline values for at least three measurements in Rome Consensus [ 16 ]. They reported that seven of nine patients with CIPO (78%) were positive for SIBO. Additionally, Lili et al. reported the usefulness of FMT in their study. In 2017, the North American Consensus criteria for SIBO was proposed [ 12 ]. In that consensus, a rise in hydrogen of ≥ 20 ppm in 90 min during glucose or lactulose BT for SIBO was considered positive. Methane levels ≥ 10 ppm were considered methane-positive. Recently, the use of glucose breath tests (GBTs) has become mainstream. The LBT is based on an incorrect premise; therefore, incorrect interpretations have resulted in the overdiagnosis of SIBO and the excessive use of antibiotics in clinical practice. Therefore, the GBT should be used when considering SIBO in patients [ 18 ]. In 2021, Khan et al. conducted a study using the North American Consensus in GBT and reported that methane-type SIBO (53%) was more common in patients with CIPO, while the rate of hydrogen-type SIBO (24%) was not different from that in the control group [ 8 ]. In contrast, Okubo et al. reported a 67% incidence of hydrogen-type SIBO using the Rome Consensus in a 2024 GBT study [ 11 ]. Okubo et al. also noted the usefulness of rifaximin in their research. However, this study investigated only hydrogen gas and did not measure methane gas. There are no data on methane gas measurements in Asian patients with CIPO; therefore, we measured hydrogen and methane gas using GBT according to the North American Consensus. Unlike the report by Khan et al., methane-type SIBO was not present in Japanese patients with CIPO, and hydrogen-type SIBO was significantly higher (50%) than in the healthy group. Patients who tested positive for hydrogen-type SIBO had a higher rate (40%) of diarrhea symptoms than did those who tested negative. Methanogenic flora has been implicated in the slow transit of intestinal nutrients [ 19 ]. In a case-control study by Attaluri et al., methane positivity during breath testing was significantly associated with chronic constipation [ 20 ]. Similarly, a large meta-analysis showed that patients with irritable bowel syndrome with constipation had a three times higher prevalence of methane-positive SIBO compared with patients with irritable bowel syndrome with diarrhea [ 21 ]. The difference between the results of Khan’s study and our research may be due to cultural factors, such as dietary differences in fiber, as the prevalence of constipation is recognized to be lower in Asia compared to the West [ 22 ]. Of the 10 healthy individuals used as controls, only one tested positive for methane SIBO. He had lived in the UK for a year and was tested immediately after returning to Japan. Given that he is Japanese, the genetic influence was unlikely, suggesting that diet played a major role. Treatment for SIBO involves antibiotics, probiotics, diet, and treatment of the predisposing conditions when possible [ 23 ]. Recently, antibiotics such as rifaximin or metronidazole have been proposed to improve SIBO treatment [ 11 , 14 , 24 , 25 ]. Therefore, we used metronidazole, which has been reported to be effective against SIBO, and found it to be effective in treating some of our patients with CIPO and SIBO. One limitation of this study is that all reports were based on a small number of cases; therefore, further studies with larger cohorts are needed to validate these findings. In conclusion, this is the first report of methane and hydrogen SIBO in Asian patients with CIPO. This study performed glucose-loading hydrogen and methane breath tests in patients with CIPO, a rare disease and showed that, contrary to previous reports, methane-type SIBO is rare, and hydrogen-type SIBO is common in Japanese patients. Furthermore, our study suggests that metronidazole may be effective in treating patients with SIBO-positive CIPO. Declarations Ethics approval and consent to participate: The study was reviewed and approved by the Institutional Review Board of Niigata University. Consent for publication: Written informed consent was obtained from the patient for publication of the report and accompanying images. Availability of data and materials: Not applicable. Conflict of interest: Funding: This study received financial support from the Takeda Science Foundation and a Grant-in-Aid for Young Scientific Research (19K17393) from the Ministry of Education, Science, Technology, and Sports. Author’s contributions: TI, KT, KY, TW, HY, YK, NK, YK, KT and AS diagnosed and drafted the manuscript. KI, KT, and ST analyzed the data. All the authors critically reviewed the manuscript and approved the final draft. Acknowledgments This study received financial support from the Takeda Science Foundation and a Grant-in-Aid for Young Scientific Research (19K17393) from the Ministry of Education, Science, Technology, and Sports. References Dudley HA, Sinclair IS, McLaren IF, McNair TJ, Newsam JE (1958) Intestinal pseudo-obstruction. J R Coll Surg Edinb 3:206–217 Antonucci A, Fronzoni L, Cogliandro L et al (2008) Chronic intestinal pseudo-obstruction. 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Aliment Pharmacol Ther 45:604–616. https://doi.org/10.1111/apt.13928 Richard N, Desprez C, Wuestenberghs F, Leroi AM, Gourcerol G, Melchior C (2021) The effectiveness of rotating versus single course antibiotics for small intestinal bacterial overgrowth. United European Gastroenterol J 9:645–654. https://doi.org/10.1002/ueg2.12116 Tables Tables 1 and 2 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table1.tif Table 1. Summary of patient characteristics. BMI; Body Mass Index, SIBO; Small Intestinal Bacterial Overgrowth, CIPO; Chronic Intestinal Pseudo-Obstruction Table2.tif Table 2. Summary of previous reports on CIPO and SIBO. SIBO; Small Intestinal Bacterial Overgrowth, CIPO; Chronic Intestinal Pseudo-Obstruction, LBT; Lactulose Breath Test, GBT; Glucose Breath Test, FMT; Fecal Microbiota Transplantation, RFX; Rifaximin, MNZ; Metronidazole. 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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-6928176","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":478071866,"identity":"44363489-6e81-434f-be6d-4105edb0b60d","order_by":0,"name":"Takanori Igarashi","email":"","orcid":"","institution":"Niigata University","correspondingAuthor":false,"prefix":"","firstName":"Takanori","middleName":"","lastName":"Igarashi","suffix":""},{"id":478071867,"identity":"947473c7-fb63-4f4f-ad92-e7e69ecefa83","order_by":1,"name":"Kentaro Tominaga","email":"data:image/png;base64,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","orcid":"","institution":"Niigata University","correspondingAuthor":true,"prefix":"","firstName":"Kentaro","middleName":"","lastName":"Tominaga","suffix":""},{"id":478071868,"identity":"98d7a4bc-8593-4b69-ad95-2c355ae8673b","order_by":2,"name":"Kunihiko Yokoyama","email":"","orcid":"","institution":"Niigata University","correspondingAuthor":false,"prefix":"","firstName":"Kunihiko","middleName":"","lastName":"Yokoyama","suffix":""},{"id":478071869,"identity":"7ebaa5e8-e740-4451-afab-8ea84d07471b","order_by":3,"name":"Takuya Wakabayashi","email":"","orcid":"","institution":"Niigata University","correspondingAuthor":false,"prefix":"","firstName":"Takuya","middleName":"","lastName":"Wakabayashi","suffix":""},{"id":478071870,"identity":"71d4a5f6-5f04-46c1-a855-efbd9d1fdd89","order_by":4,"name":"Hanako Yamazaki","email":"","orcid":"","institution":"Niigata University","correspondingAuthor":false,"prefix":"","firstName":"Hanako","middleName":"","lastName":"Yamazaki","suffix":""},{"id":478071871,"identity":"7fc2e35c-218a-4848-9870-0526a69485e8","order_by":5,"name":"Yuichi Kojima","email":"","orcid":"","institution":"Niigata University","correspondingAuthor":false,"prefix":"","firstName":"Yuichi","middleName":"","lastName":"Kojima","suffix":""},{"id":478071872,"identity":"a9d272f1-9b24-412d-b8f7-f32747bf7875","order_by":6,"name":"Yuzo Kawata","email":"","orcid":"","institution":"Niigata University","correspondingAuthor":false,"prefix":"","firstName":"Yuzo","middleName":"","lastName":"Kawata","suffix":""},{"id":478071875,"identity":"ce872983-f219-4c8e-958d-85e559cf2abe","order_by":7,"name":"Naruhiro Kimura","email":"","orcid":"","institution":"Niigata University","correspondingAuthor":false,"prefix":"","firstName":"Naruhiro","middleName":"","lastName":"Kimura","suffix":""},{"id":478071877,"identity":"e0246f6f-ede2-4d58-b7bd-d91fa92d0662","order_by":8,"name":"Kazuya Takahashi","email":"","orcid":"","institution":"Niigata University","correspondingAuthor":false,"prefix":"","firstName":"Kazuya","middleName":"","lastName":"Takahashi","suffix":""},{"id":478071879,"identity":"ca1c64f7-e006-4035-a30f-5f154f33c793","order_by":9,"name":"Akira Sakamaki","email":"","orcid":"","institution":"Niigata University","correspondingAuthor":false,"prefix":"","firstName":"Akira","middleName":"","lastName":"Sakamaki","suffix":""},{"id":478071880,"identity":"a4b98e21-6f87-4f06-b7ea-7d80186cb608","order_by":10,"name":"Shuji Terai","email":"","orcid":"","institution":"Niigata University","correspondingAuthor":false,"prefix":"","firstName":"Shuji","middleName":"","lastName":"Terai","suffix":""}],"badges":[],"createdAt":"2025-06-19 06:53:14","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-6928176/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6928176/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":85917780,"identity":"5dbebc14-e177-4b73-8221-3e54d75b0e98","added_by":"auto","created_at":"2025-07-03 07:12:08","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":94080,"visible":true,"origin":"","legend":"\u003cp\u003ea Actual breath test measurement scene. b Equipment required for SIBO breath testing. SIBO: Small Intestinal Bacterial Overgrowth.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6928176/v1/a91a84a95ce5bb16af0d7d1c.jpg"},{"id":85917783,"identity":"79877a58-0107-4564-8ee2-21af280aa58d","added_by":"auto","created_at":"2025-07-03 07:12:08","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":141875,"visible":true,"origin":"","legend":"\u003cp\u003ea Abdominal radiograph: marked distension of the intestine by intestinal gas is seen. Small intestinal gas occupies the most part. b Abdominal CT: markedly dilated intestinal loops and air-fluid levels are seen. c Cine-MRI: small bowel dilatation and reduced peristalsis are seen. d: A breath test confirmed the diagnosis of hydrogen-type SIBO according to the North American Consensus\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6928176/v1/90249418115bede7140fec5e.jpg"},{"id":85917786,"identity":"b8c41398-4760-4e66-9d41-ed63055219fe","added_by":"auto","created_at":"2025-07-03 07:12:08","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":112558,"visible":true,"origin":"","legend":"\u003cp\u003ea Prevalence of SIBO in CIPO patients and healthy controls. b Flowchart before and after treatment for SIBO-positive patients. SIBO: Small Intestinal Bacterial Overgrowth; CIPO: Chronic Intestinal Pseudo-Obstruction; FODMAP: Fermentable Oligosaccharides Disaccharides, Monosaccharides, and Polyols.\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6928176/v1/999df19e3612d4add6fdbc68.jpg"},{"id":89258832,"identity":"8c481c8a-e5c2-42d5-b445-59630acda69e","added_by":"auto","created_at":"2025-08-18 06:24:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":834253,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6928176/v1/984d8e0b-3922-4869-a768-d67b376649d7.pdf"},{"id":85917781,"identity":"4bb25427-a19c-4cc2-87d5-ea6c9902e74e","added_by":"auto","created_at":"2025-07-03 07:12:08","extension":"tif","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":68586,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e. Summary of patient characteristics. BMI; Body Mass Index, SIBO; Small Intestinal Bacterial Overgrowth, CIPO; Chronic Intestinal Pseudo-Obstruction\u003c/p\u003e","description":"","filename":"Table1.tif","url":"https://assets-eu.researchsquare.com/files/rs-6928176/v1/8d64d829bd01ff732fefee7c.tif"},{"id":85918097,"identity":"7f3c9061-04bf-4c4d-9295-ae14d8fc8251","added_by":"auto","created_at":"2025-07-03 07:20:08","extension":"tif","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":60004,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e. Summary of previous reports on CIPO and SIBO. SIBO; Small Intestinal Bacterial Overgrowth, CIPO; Chronic Intestinal Pseudo-Obstruction, LBT; Lactulose Breath Test, GBT; Glucose Breath Test, FMT; Fecal Microbiota Transplantation, RFX; Rifaximin, MNZ; Metronidazole.\u003c/p\u003e","description":"","filename":"Table2.tif","url":"https://assets-eu.researchsquare.com/files/rs-6928176/v1/c5df5d8a1f5e7be6b432fd45.tif"}],"financialInterests":"No competing interests reported.","formattedTitle":"Chronic intestinal pseudo‑obstruction is associated with small intestinal bacterial overgrowth","fulltext":[{"header":"Introduction","content":"\u003cp\u003eChronic intestinal pseudo-obstruction (CIPO) is a rare clinical syndrome that was first reported by Dudley et al. in 1958 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. CIPO is a functional motility disorder characterized by episodic obstructive symptoms without a mechanical cause. However, its etiology and causes are not well understood.\u003c/p\u003e \u003cp\u003eCIPO has been increasingly identified as a cause of chronic malabsorption and intestinal failure [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. When impairment of gut motility and transit is severe, small intestinal bacterial overgrowth (SIBO) may occur, further contributing to malnutrition [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Notably, SIBO may exacerbate intestinal dysmotility [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Emerging evidence suggests an association between CIPO and SIBO [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. A study conducted in Chile explored this association and found that the prevalence of SIBO (hydrogen type) in 40 patients with CIPO is 60% [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. However, at that time, methane was not measured; only hydrogen was measured. Subsequent advancements in our understanding of the gut microbiome and the availability of breath tests for measuring hydrogen and methane have facilitated the study of the physiological effects of these gases on different SIBO phenotypes and their associated clinical symptoms. Due to the contrasting effects of methane and hydrogen on intestinal motility and variable manifestations, excessive methane production has led to the adoption of the term \u0026ldquo;intestinal methanogen overgrowth\u0026rdquo; (IMO) [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Nonetheless, there are limited studies on the prevalence of hydrogen and methane-producing bacterial overgrowth subtypes in patients with CIPO [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Additionally, data exploring the demographics and clinical characteristics of patients with CIPO and SIBO are limited. Our previous reports indicate an association between patients with cirrhosis and SIBO [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. This study aimed to identify and compare the prevalence of hydrogen and methane production in patients with CIPO. We present our findings alongside a review of previous studies.\u003c/p\u003e"},{"header":"Material and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSubjects and study protocol\u003c/h2\u003e \u003cp\u003eThis cross-sectional and prospective cohort study was conducted at Niigata University. This study was approved by the ethical review board of Niigata University (Approval Number 2019\u0026ndash;0226). Patients screened for the study were those admitted or visited due to CIPO between April 2019 and May 2025. Patients (aged 18 years or older) who were diagnosed with CIPO according to all relevant diagnostic criteria proposed by the Japanese Ministry of Health, Labor, and Welfare [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], including documented pathological bowel dilatation in the absence of mechanical obstruction on imaging, were recruited. CIPO is classified as either primary (no underlying cause identified) or secondary (known cause determined, such as systemic sclerosis or drug-induced).\u003c/p\u003e \u003cp\u003eOverall, 10 patients were included in this study. All patients agreed to participate in the study and provided written informed consent. Moreover, 10 healthy controls with no symptoms and no history of underlying diseases or surgery wishing to undergo SIBO testing participated. The authors ensure that this study is conducted in accordance with the principles of the Declaration of Helsinki and with ethical guidelines for medical and biological research involving human subjects in Japan.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eDiagnosis of SIBO\u003c/h3\u003e\n\u003cp\u003eIn this study, a breath test was performed to diagnose SIBO. For accurate diagnosis, bread, pasta, and noodles, which increase hydrogen production, were not allowed for 24 h prior to the breath test. In addition, oral intake of water or tea was not allowed for 12 h prior to the test. Regular medications were administered 2 h before the test, if necessary, and participants were advised to avoid drinking, exercising, and smoking during this period. Oral rinsing was performed to avoid the metabolism of sugar substrates by oral bacteria. Breath measurements (hydrogen and methane concentrations) were performed three times before sugar substrate loading, and the average score was used as the baseline. Subsequently, breath measurements were performed every 15 min after loading and up to 120 or 180 min. The sugar substrate used was 50 g of glucose. Exhaled hydrogen and methane concentrations were measured using a BGA2000D instrument (Laboratory for Expiration Biochemistry Nourishment Metabolism Co., Ltd., Nara, Japan) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea, b).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAccording to the North American consensus [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], the following two diagnostic criteria for SIBO were used: a rise of \u0026ge;\u0026thinsp;20 ppm from baseline in hydrogen by 90 min and a level of \u0026ge;\u0026thinsp;10 ppm in methane. We have previously used these criteria to report the association between patients with cirrhosis and SIBO [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. ΔH\u003csub\u003e2\u003c/sub\u003e in Table\u0026nbsp;1 refers to the increase in hydrogen concentration from the baseline, and the CH\u003csub\u003e4\u003c/sub\u003e peak value represents the highest methane concentration. Furthermore, cases with elevated hydrogen levels were defined as H-SIBOs, while those with elevated methane levels were defined as M-SIBOs, as previously reported [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. M-SIBO is synonymous with IMO. In this study, both hydrogen- and methane-positive cases were included in the positive group for each sub-analysis.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eContinuous and categorical variables are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SE and number (%), respectively. Pearson's chi-square test and Mann\u0026ndash;Whitney U test were used for statistical analyses with the SPSS statistical package (version 24.0; IBM SPSS Japan Inc., Tokyo, Japan). Statistical significance was set at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe study included 10 patients with CIPO, comprising four males and six females, with a mean age of 48.1\u0026thinsp;\u0026plusmn;\u0026thinsp;13.6 years and a mean duration of illness of 32.7\u0026thinsp;\u0026plusmn;\u0026thinsp;35.5 months. The mean body mass index (BMI) of patients with CIPO was 16.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5 kg/m\u0026sup2;, and eight out of 10 were underweight (BMI\u0026thinsp;\u0026lt;\u0026thinsp;18.5), according to the Japan Society for the Study of Obesity (Table\u0026nbsp;1). Conversely, the mean age and BMI of the healthy controls were 31.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2 years and 22.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5 kg/m\u0026sup2;, respectively. The characteristics of CIPO were secondary in seven cases and primary in three cases. The underlying diseases associated with secondary CIPO included systemic sclerosis (one case), familial Mediterranean fever (one case), polymyositis (one case), Hashimoto disease (one case), pregnancy (two cases), and schizophrenia (drug-induced) (one case). The affected site was the small intestine in seven cases and the large intestine in three cases.\u003c/p\u003e \u003cp\u003eAbdominal radiographs, computed tomography, cine-magnetic resonance imaging (MRI), and breath test results for a representative case of CIPO are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. This is a case of secondary intestinal pseudo-obstruction that developed in a 31-year-old woman after pregnancy and childbirth (Case No. 5). The symptoms included abdominal pain, bloating, and diarrhea. Abdominal radiography revealed significant gaseous distension, predominantly in the small intestine. Abdominal radiographs and computed tomography demonstrated markedly dilated intestinal loops with air-fluid levels (Fig, 2a, b). Cine-MRI revealed small bowel dilatation and reduced peristalsis (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ec). A breath test confirmed the diagnosis of hydrogen-type SIBO, according to the North American Consensus (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn our study, as a result of hydrogen/methane breath tests, five out of 10 cases were SIBO-positive using the North American Consensus (six out of 10 using the Rome Consensus [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]), and all cases were associated with SIBO-phenotype hydrogen type. Excluding two cases of colonic CIPO (cases no. 7 and 10) undergoing postoperative follow-up, five of eight cases (62.5%) of untreated CIPO were positive for hydrogen-type SIBO.\u003c/p\u003e \u003cp\u003eIn contrast, when SIBO was measured in 10 healthy controls (male to female ratio 8:2, average age 31.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.22 years, average BMI 22.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.46, no symptoms, no history of underlying diseases or surgery), only one case was diagnosed as having methane SIBO, and no participant was diagnosed with hydrogen SIBO. The rate of SIBO was significantly higher in the CIPO group than in the healthy control group (50% vs. 10%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) (Fig, 3a).\u003c/p\u003e \u003cp\u003eAmong patients with CIPO, SIBO-positive individuals tended to have a lower BMI than did SIBO-negative participants (SIBO-positive vs. SIBO-negative; 15.6 kg/m\u003csup\u003e2\u003c/sup\u003e vs. 18.0 kg/m\u003csup\u003e2\u003c/sup\u003e), with no difference in age or sex. The symptoms observed included abdominal pain, abdominal fullness, nausea, diarrhea, and constipation. SIBO-positive patients were relatively more likely to complain of abdominal pain and nausea than SIBO-negative patients. Furthermore, while no H-SIBO-negative patients experienced diarrhea, this symptom was observed in two out of five H-SIBO-positive patients. Patients who tested positive for hydrogen-type SIBO had a higher rate (40%) of diarrhea symptoms than did those who tested negative.\u003c/p\u003e \u003cp\u003eOf the five SIBO-positive patients, case 2 underwent colostomy, and cases 1 and 5 were treated with metronidazole, which improved their symptoms (Fig, 3b). After treatment, SIBO was measured, and two (Case 1 and Case 2) out of the three patients tested negative. Cases 3 and 4 were treated with a low Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols (FODMAP) diet; however, SIBO testing was not performed after treatment due to patient preference.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo date, limited reports have been published on the relationship between CIPO and SIBO (Table\u0026nbsp;2). In 2014, P\u0026eacute;rez et al. first reported the incidence of SIBO in patients with CIPO [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Using breath hydrogen concentration measurements from the lactulose hydrogen breath test (LBT), SIBO was detected in 60% of 40 patients with CIPO. However, at that time, methane was not measured; only hydrogen was recorded, and SIBO using the LBT was defined as an increase of \u0026gt;\u0026thinsp;20 ppm in two or more figures in the first 60 min.\u003c/p\u003e \u003cp\u003eIn 2017, Lili et al. measured hydrogen gas in the breath of patients with CIPO using the LBT and verified it using the Rome Consensus [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. SIBO was diagnosed if breath concentrations of hydrogen or methane were \u0026ge;\u0026thinsp;12 ppm over baseline values for at least three measurements in Rome Consensus [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. They reported that seven of nine patients with CIPO (78%) were positive for SIBO. Additionally, Lili et al. reported the usefulness of FMT in their study.\u003c/p\u003e \u003cp\u003eIn 2017, the North American Consensus criteria for SIBO was proposed [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In that consensus, a rise in hydrogen of \u0026ge;\u0026thinsp;20 ppm in 90 min during glucose or lactulose BT for SIBO was considered positive. Methane levels\u0026thinsp;\u0026ge;\u0026thinsp;10 ppm were considered methane-positive. Recently, the use of glucose breath tests (GBTs) has become mainstream. The LBT is based on an incorrect premise; therefore, incorrect interpretations have resulted in the overdiagnosis of SIBO and the excessive use of antibiotics in clinical practice. Therefore, the GBT should be used when considering SIBO in patients [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn 2021, Khan et al. conducted a study using the North American Consensus in GBT and reported that methane-type SIBO (53%) was more common in patients with CIPO, while the rate of hydrogen-type SIBO (24%) was not different from that in the control group [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn contrast, Okubo et al. reported a 67% incidence of hydrogen-type SIBO using the Rome Consensus in a 2024 GBT study [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Okubo et al. also noted the usefulness of rifaximin in their research. However, this study investigated only hydrogen gas and did not measure methane gas.\u003c/p\u003e \u003cp\u003eThere are no data on methane gas measurements in Asian patients with CIPO; therefore, we measured hydrogen and methane gas using GBT according to the North American Consensus. Unlike the report by Khan et al., methane-type SIBO was not present in Japanese patients with CIPO, and hydrogen-type SIBO was significantly higher (50%) than in the healthy group. Patients who tested positive for hydrogen-type SIBO had a higher rate (40%) of diarrhea symptoms than did those who tested negative. Methanogenic flora has been implicated in the slow transit of intestinal nutrients [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In a case-control study by Attaluri et al., methane positivity during breath testing was significantly associated with chronic constipation [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Similarly, a large meta-analysis showed that patients with irritable bowel syndrome with constipation had a three times higher prevalence of methane-positive SIBO compared with patients with irritable bowel syndrome with diarrhea [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The difference between the results of Khan\u0026rsquo;s study and our research may be due to cultural factors, such as dietary differences in fiber, as the prevalence of constipation is recognized to be lower in Asia compared to the West [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Of the 10 healthy individuals used as controls, only one tested positive for methane SIBO. He had lived in the UK for a year and was tested immediately after returning to Japan. Given that he is Japanese, the genetic influence was unlikely, suggesting that diet played a major role.\u003c/p\u003e \u003cp\u003eTreatment for SIBO involves antibiotics, probiotics, diet, and treatment of the predisposing conditions when possible [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Recently, antibiotics such as rifaximin or metronidazole have been proposed to improve SIBO treatment [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Therefore, we used metronidazole, which has been reported to be effective against SIBO, and found it to be effective in treating some of our patients with CIPO and SIBO.\u003c/p\u003e \u003cp\u003eOne limitation of this study is that all reports were based on a small number of cases; therefore, further studies with larger cohorts are needed to validate these findings.\u003c/p\u003e \u003cp\u003eIn conclusion, this is the first report of methane and hydrogen SIBO in Asian patients with CIPO. This study performed glucose-loading hydrogen and methane breath tests in patients with CIPO, a rare disease and showed that, contrary to previous reports, methane-type SIBO is rare, and hydrogen-type SIBO is common in Japanese patients. Furthermore, our study suggests that metronidazole may be effective in treating patients with SIBO-positive CIPO.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eThe study was reviewed and approved by the Institutional Review Board of Niigata University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e Written informed consent was obtained from the patient for publication of the report and accompanying images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis study received financial support from the Takeda Science Foundation and a Grant-in-Aid for Young Scientific Research (19K17393) from the Ministry of Education, Science, Technology, and Sports.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor\u0026rsquo;s contributions:\u0026nbsp;\u003c/strong\u003eTI, KT, KY, TW, HY, YK, NK, YK, KT and AS diagnosed and drafted the manuscript. KI, KT, and ST analyzed the data. All the authors critically reviewed the manuscript and approved the final draft.\u003c/p\u003e\u003ch2\u003eAcknowledgments\u003c/h2\u003e \u003cp\u003eThis study received financial support from the Takeda Science Foundation and a Grant-in-Aid for Young Scientific Research (19K17393) from the Ministry of Education, Science, Technology, and Sports.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDudley HA, Sinclair IS, McLaren IF, McNair TJ, Newsam JE (1958) Intestinal pseudo-obstruction. J R Coll Surg Edinb 3:206\u0026ndash;217\u003c/li\u003e\n\u003cli\u003eAntonucci A, Fronzoni L, Cogliandro L et al (2008) Chronic intestinal pseudo-obstruction. World J Gastroenterol 14:2953\u0026ndash;2961. https://doi.org/10.3748/wjg.14.2953\u003c/li\u003e\n\u003cli\u003eLauro A, De Giorgio R, Pinna AD (2015) Advancement in the clinical management of intestinal pseudo-obstruction. Expert Rev Gastroenterol Hepatol 9:197\u0026ndash;208. https://doi.org/10.1586/17474124.2014.940317\u003c/li\u003e\n\u003cli\u003eShimura S, Ishimura N, Mikami H, et al (2016) Small Intestinal Bacterial Overgrowth in Patients with Refractory Functional Gastrointestinal Disorders. J Neurogastroenterol Motil 22:60\u0026ndash;68. https://doi.org/10.5056/jnm15116\u003c/li\u003e\n\u003cli\u003eSingh R, Zogg H, Wei L, Bartlett A, Ghoshal UC, Rajender S, Ro S (2021) Gut microbial dysbiosis in the pathogenesis of gastrointestinal dysmotility and metabolic disorders. J Neurogastroenterol Motil 27:19\u0026ndash;34. https://doi.org/10.5056/jnm20149\u003c/li\u003e\n\u003cli\u003eP\u0026eacute;rez de Arce OE, Defilippi CC, Madrid SA (2014) Accessed 2014 Sobrecrecimiento bacteriano intestinal y pseudoobstrucci\u0026oacute;n intestinal cr\u0026oacute;nica: una relaci\u0026oacute;n poco conocida. Pesquisa. bvsalud.org. https:// pesqu isa. http://bvsalud.org/portal/resource/pt/lil-766592\u003c/li\u003e\n\u003cli\u003eTriantafyllou K, Chang C, Pimentel M (2014) Methanogens, methane and gastrointestinal motility. J Neurogastroenterol Motil 20:31\u0026ndash;40. https://doi.org/10.5056/jnm.2014.20.1.31\u003c/li\u003e\n\u003cli\u003eKhan MZ, Lyu R, McMichael J, Gabbard S (2022) Chronic intestinal pseudo-obstruction is associated with intestinal methanogen overgrowth. Dig Dis Sci 67:4834\u0026ndash;4840. https://doi.org/10.1007/s10620-021-07343-1\u003c/li\u003e\n\u003cli\u003eSakamaki A, Yokoyama K, Yamazaki H, Wakabayashi T, Kojima Y, Tominaga K, Tsuchiya A, Kamimura K, Yokoyama J, Terai S (2025) Small intestinal bacterial overgrowth Is a predictor of overt hepatic encephalopathy in patients with liver cirrhosis. J Clin Med 14:1491. https://doi.org/10.3390/jcm14051491\u003c/li\u003e\n\u003cli\u003eYokoyama K, Sakamaki A, Takahashi K, Naruse T, Sato C, Kawata Y, Tominaga K, Abe H, Sato H, Tsuchiya A, Kamimura K, Takamura M, Yokoyama J, Terai S (2022) Hydrogen-producing small intestinal bacterial overgrowth is associated with hepatic encephalopathy and liver function. PLoS One 17:e0264459. https://doi.org/10.1371/journal.pone.0264459\u003c/li\u003e\n\u003cli\u003eOhkubo H, Iida H, Takahashi H, et al (2012) An epidemiologic survey of chronic intestinal pseudo-obstruction and evaluation of the newly proposed diagnostic criteria. Digestion 86:12\u0026ndash;19. https://doi.org/10.1159/000337528\u003c/li\u003e\n\u003cli\u003eRezaie A, Buresi M, Lembo A et al (2017) Hydrogen and methane-based breath testing in gastrointestinal disorders: the North American Consensus. Am J Gastroenterol 112:775\u0026ndash;784. https://doi.org/10.1038/ajg.2017.46\u003c/li\u003e\n\u003cli\u003ePimentel M, Saad RJ, Long MD, Rao SSC (2020) ACG clinical guideline: small intestinal bacterial overgrowth. Am J Gastroenterol 115:165\u0026ndash;178. https://doi.org/10.14309/ajg.0000000000000501\u003c/li\u003e\n\u003cli\u003eSakamaki A, Yokoyama K, Yamazaki F, Kamimura H, Kamimura K, Takamura M, Yokoyama J, Terai S (2020) Small intestinal bacterial overgrowth diagnosed by a breath test and improved by rifaximin in a patient with hepatic encephalopathy and alcoholic liver cirrhosis. Intern Med 59:1849-1853. https://doi.org/10.2169/internalmedicine.4593-20\u003c/li\u003e\n\u003cli\u003eSuri J, Kataria R, Malik Z, Parkman HP, Schey R (2018) Elevated methane levels in small intestinal bacterial overgrowth suggests delayed small bowel and colonic transit. Med (Baltim) 97:e10554. https://doi.org/10.1097/MD.0000000000010554\u003c/li\u003e\n\u003cli\u003eGasbarrini A, Corazza GR, Gasbarrini G, et al (2009) Methodology and indications of H2-breath testing in gastrointestinal diseases: the Rome Consensus Conference. Aliment Pharmacol Ther 29(suppl 1):1\u0026ndash;49. https://doi.org/10.1111/j.1365-2036.2009.03951.x\u003c/li\u003e\n\u003cli\u003eGu L, Ding C, Tian H, et al (2017 Apr 30) Serial frozen fecal microbiota transplantation in the treatment of chronic intestinal pseudo-obstruction: A preliminary study. J Neurogastroenterol Motil 23:289\u0026ndash;297. https://doi.org/10.5056/jnm16074\u003c/li\u003e\n\u003cli\u003eMassey BT, Wald A (2021) Small intestinal bacterial overgrowth syndrome: A guide for the appropriate use of breath testing. Dig Dis Sci 66:338\u0026ndash;347. https://doi.org/10.1007/s10620-020-06623-6\u003c/li\u003e\n\u003cli\u003eKunkel D, Basseri RJ, Makhani MD, Chong K, Chang C, Pimentel M (2011) Methane on breath testing is associated with constipation: a systematic review and meta-analysis. Dig Dis Sci 56:1612\u0026ndash;1618. https://doi.org/10.1007/s10620-011-1590-5\u003c/li\u003e\n\u003cli\u003eAttaluri A, Jackson M, Valestin J, Rao SSC (2010) Methanogenic flora is associated with altered colonic transit but not stool characteristics in constipation without IBS. Am J Gastroenterol 105:1407\u0026ndash;1411. https://doi.org/10.1038/ajg.2009.655\u003c/li\u003e\n\u003cli\u003eShah A, Talley NJ, Jones M, et al (2020) Small intestinal bacterial overgrowth in irritable bowel syndrome: A systematic review and meta-analysis of case-control studies. Am J Gastroenterol 115:190\u0026ndash;201. https://doi.org/10.14309/ajg.0000000000000504\u003c/li\u003e\n\u003cli\u003eChuah KH, Mahadeva S (2018) Cultural factors influencing functional gastrointestinal disorders in the East. J Neurogastroenterol Motil 24:536\u0026ndash;543. https://doi.org/10.5056/jnm18064\u003c/li\u003e\n\u003cli\u003eRezaie A, Pimentel M, Rao SS (2016) How to test and treat small intestinal bacterial overgrowth: an evidence‐based approach. Curr Gastroenterol Rep 18:8. https://doi.org/10.1007/s11894-015-0482-9\u003c/li\u003e\n\u003cli\u003eGatta L, Scarpignato C (2017) Systematic review with meta-analysis: Rifaximin is effective and safe for the treatment of small intestine bacterial overgrowth. Aliment Pharmacol Ther 45:604\u0026ndash;616. https://doi.org/10.1111/apt.13928\u003c/li\u003e\n\u003cli\u003eRichard N, Desprez C, Wuestenberghs F, Leroi AM, Gourcerol G, Melchior C (2021) The effectiveness of rotating versus single course antibiotics for small intestinal bacterial overgrowth. United European Gastroenterol J 9:645\u0026ndash;654. https://doi.org/10.1002/ueg2.12116\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 and 2 are available in the Supplementary Files section.\u003c/p\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":true,"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 intestinal pseudo‑obstruction, Small intestinal bacterial overgrowth, Breath tests, Hydrogen, Methanogen, Metronidazole","lastPublishedDoi":"10.21203/rs.3.rs-6928176/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6928176/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eSmall intestinal bacterial overgrowth (SIBO) is associated with various gastrointestinal diseases; however, its relationship with chronic intestinal pseudo-obstruction (CIPO) remains unclear. This study aimed to determine the prevalence and characteristics of SIBO in CIPO.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eBetween April 2019 and May 2025, we conducted a cross-sectional and prospective cohort study involving 10 outpatients diagnosed with CIPO at our hospital and 10 healthy controls. SIBO was diagnosed using a glucose-loaded hydrogen/methane breath test according to the North American Consensus criteria. We investigated the prevalence and clinical characteristics of SIBO in patients with CIPO.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe 10 patients with CIPO comprised four males and six females, with a mean age of 48.1\u0026thinsp;\u0026plusmn;\u0026thinsp;13.6 years. CIPO characteristics were secondary and primary in seven and three cases, respectively; the affected site was the small and large intestine in seven and three cases, respectively. Five of the 10 patients with CIPO were SIBO-positive, and all of them had the hydrogen-type phenotype; SIBO rate was significantly higher in patients with CIPO than in healthy participants (50% vs. 10%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). In CIPO, hydrogen-type SIBO-positive patients tended to have a lower body mass index and stronger diarrhea symptoms than did hydrogen-type SIBO-negative patients. In one case, metronidazole was effective, and the SIBO test result was negative after treatment.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThis is the first report of methane and hydrogen SIBO in Asian patients with CIPO. Hydrogen-type SIBO is more common than methane-type SIBO in Japanese patients with CIPO.\u003c/p\u003e","manuscriptTitle":"Chronic intestinal pseudo‑obstruction is associated with small intestinal bacterial overgrowth","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-03 07:12:03","doi":"10.21203/rs.3.rs-6928176/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":"5f65d831-1e49-4a1c-9f52-621ed1c119b1","owner":[],"postedDate":"July 3rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-18T06:23:45+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-03 07:12:03","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6928176","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6928176","identity":"rs-6928176","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}