Virgin Olive Oil Extract as anti-inflammatory on Patients with Chronic Kidney Disease: Analysis of Neutrophil-to-lymphocyte Ratio and Short-Chain Fatty Acid

Virgin Olive Oil Extract as anti-inflammatory on Patients with Chronic Kidney Disease: Analysis of Neutrophil-to-lymphocyte Ratio and Short-Chain Fatty Acid | 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 Virgin Olive Oil Extract as anti-inflammatory on Patients with Chronic Kidney Disease: Analysis of Neutrophil-to-lymphocyte Ratio and Short-Chain Fatty Acid Mely Marita MZ, Haerani Rasyid, Nurpudji Astuti Taslim, Suryani As’ad, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4576443/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 and objective : People with Chronic Kidney Disease (CKD) generally has malnutrition and decrease immune system due to lower food intake and inflammation. To address the progression of CKD, the Neutrophil-to-Lymphocyte Ratio (NLR) has been identified as an independent risk factor. The decrease in short-chain fatty acids (SCFAs) in the feces and serum of CKD patients during disease progression suggests a link between gut microbiota and CKD. We proposed administering Extra Virgin Olive Oil (EVOO) to explore the impact of the intervention CKD patients and effects on inflammation and gut microbiota. Methods This study was randomized clinical trial design by the administration of EVOO. Thirty participants were taken from CKD patients undergoing hemodialysis (HD). The intervention group (15 participants) was administered with EVOO 40ml for 2 weeks, and 15 participants as a control group without EVOO. Body mass index was measured using anthropometric (body weigth dan heigth), NLR were taken from red blood cell and SCFA using prohealthy gut examination, Results the study showed there were no differences between two group on nutritional status (both had normal status). Level of NRL significantly differents pre-and-post in intervention group, (5.07 ± 7.35 vs 2.74 ± 2.18 p = 0.007), not for control group ( 3.86 ± 2.21vs 4.26 ± 2.56 p = 0.196). There are not significant result for SCFA for intervention group (8.31 ± 3.77 vs 8.92 ± 3.88 p = 0.670). and control group (11.50 ± 4.80 vs 11.50 ± 3.86 p = 0.550). in addition, this study shown significant increased of energy intake, and carbohydrate on intervention group not in control group (p < 0,005). Conclusion This study reported the differences of NLR and SCFA levels and food intake in both groups, NLR as inflammatory markers significantly decreased in intervention group after 2 weeks of EVOO administration, while increased in control group. Moreover, EVOO affected Short SCFA levels in the gastrointestinal tract. Nutrition & Dietetics Chronic Kidney Disease Extra Virgin Olive Oil NLR SCFA Introduction The prevalence and incidence of CKD increased with increasing incidence of diabetes mellitus and hypertension. The condition can develop into kidney failure which is a world health problem due to a poor prognosis and high cost. 1 A meta-analysis and systematic review study showed a world prevalence of CKD of 13.4% 2 and in Indonesia the number of new CKD patients increases each year, the incidence of new CKD in Indonesia until 2016 was 25,446 patients, with active patients 52,835. 3 Financing for CKD treatment in Indonesia is ranked second after heart disease 1 (BPJS). Chronic Kidney Disease is associated with immune activation characterized by systemic inflammation and immunodeficiency. 4 The composition and metabolic activity of microbiota changes in CKD due to quantitative and qualitative changes in the gut microbiota which started from the initial stage of CKD. 5 Chronic Kidney Disease patients are prone to be malnourished hence results in weight loss and immune system deficiency. Partly due to diet in low protein, sodium, vitamins, and water. 6 The human immune system plays an important role in maintaining homeostasis with the microbiota, thus ensuring that the mutualism relationship with the host can be maintained. At the same time, the microbiota plays role in the human immune system. Therefore, a new paradigm postulates that the immune system has evolved to accommodate the colonization of an increasingly complex symbiotic microbiota while still retaining the capacity to resist pathogens. How colonies of bacteria from the gut can influence the development and functioning of the immune system become interesting topic to explore. 7 Various strategies have been developed by nephrologists to slow the progressivity of CKD. Nutrition management in CKD aims to improve quality of life, reduce morbidity and mortality and slow the progressivity of kidney disease. It is recommended that CKD patients need to modify their nutritional intake. Malnutrition conditions are often found in patients with CKD and other chronic diseases. This is due to various factors, such as impaired protein and energy metabolism, micronutrient deficiencies, hormonal dysregulation, infections, anorexia, inadequate intake, and uremic syndrome. Research states that 31% of CKD patients experience protein-energy malnutrition (PEM), where severe PEM can increase the risk of death up to 5 times. 8 Neutrophil-Lymphocyte Ratio is a widely used systemic inflammatory biomarker, which can be obtained easily from a complete blood test. 9 NLR is measured by dividing the number of neutrophils by the number of lymphocytes. 10 Studies by Yoshitomi et al. , have identified NLR levels as an independent risk factor for kidney disease progression in patients with stage 1–4 CKD Thus, NLR measurements may be useful for predicting the progression of kidney disease in CKD patients. 11 It has been proven that the number of Short Chain Fatty Acid (SCFA)-producing bacteria is reduced in patients with CKD. Clinical studies investigating the potential measurement of circulating SCFA as a biological marker in diagnosis, prognosis, and therapeutic monitoring in renal patients are still rare. 12 Wang et al . showed that the main SCFAs (acetate, propionate, and butyrate) and especially butyrate were reduced in the patient's feces and serum during the development of CKD. 13 In the early stages of CKD, a "healthy diet" is recommended and is characterized by a high intake of vegetables, fruit, nuts, seeds, legumes, and fish, as well as a low intake of saturated fats and sodium. 14 The Mediterranean diet represents a nutritional dietary regimen appropriate for the initial management of CKD. Among the typical products of the Mediterranean diet, the main food is represented by EVOO which is the main source of vegetable fats. 15 EVOO consists mainly of triglycerides (97–99%) and minor compounds (1–3%). 16 Minor compounds, particularly phenolic are important for the health effects provided by EVOO. 15 Many of the health benefits of a mediterranean diet enriched with EVOO have been reported such as protecting against cardiovascular disease, antioxidant properties, anti-inflammatory, antitumor activity, and modulation of the gut microbiota. 16 In Chronic Kidney Disease, several conditions such as malnutrition and decreased body resistance are often encountered. In this study, an intervention will be carried out in the form of giving EVOO and seeing whether EVOO administration affects inflammation and intestinal microbiota of CKD patients. Method Research design This study used a randomized clinical trial, pre post test design. About 30 participants were taken from CKD patients undergoing HD who had met the inclusion criteria. Inclusion and Exclusion Criteria The inclusion criteria of study: Patients able to communicate well, understand and give written consent to participate in the study, aged > 18–65 years, patients with a diagnosis of CKD undergo routine HD less than or equal to 3 comorbidities. The exclusion criteria: Patients who are not eligible for examination, patients consuming yogurt probiotics in the last 3 months, patients with symptoms and gastrointestinal disorders (diarrhea, vomiting, IBD and gastrointestinal bleeding). Research Procedure The samples of 15 participants in the intervention group given daily EVOO 40 ml for 2 weeks, and 15 participants were included in the control group without being given EVOO (only nutritional education), 3 samples was drop out (2 intervention and 1 control ) due to the patient could not continue the procedures (did not check blood and feces on the 2nd examination). Data collection is carried out in two stages. First, screening was carried out to collected samples, then determined samples that met the inclusion and exclusion criteria, second, followed by pre-intervention and intervention examinations for 2 weeks followed by post-intervention examinations stages one and two, namely the data collected including data from all variables taken in the study. In both groups, routine blood tests for NLR and intestinal microbiota (SCFA concentration in feces) were carried out, which are the end products of volatile gastrointestinal bacterial fermentation (acetate, propionate and butyrate which have an important role in gastrointestinal health) using Pro Healthy Gut examination. Statistical analysis The data obtained is processed and analyzed statistically using SPSS 25 for Windows and the results are displayed in the form of narratives, tables or graphs. The confidence level is 95% and is considered meaningful when p < 0.05. To compare numerical data using two categories or between groups using independent t test if data is normal, Mann-Whitney test used if data is abnormal. To compare numerical data in repeated measurements, observational measurements twice (pre post) use a t-paired test if the data is normal, and the Wilcoxon test used if the data is abnormal. Result General Overview of Research Samples This research was conducted at Dr. Wahidin Sudirohusodo Hospital Makassar after obtaining ethical approval from the Health Research Ethics Committee of the Faculty of Medicine, Hasanuddin University number: 580 / UN4.6.4.5.31 / PP36 / 2022 and received permission from the hospital. This study aims to determine whether there is an effect of EVOO on NLR and SCFA inflammation markers in CKD patients. Research Subjects’ Characteristics This study involved 30 patients with CKD undergoing HD who had met the inclusion criteria. The characteristics are as follows (table 1): Mean age value in the intervention group is 49.62 year-old (13.14%) compared to the median control group age 41.57 year-old (13.22%) The gender were dominated by males; 20 males (74.1%) and 7 females (25.9%), with comparisons between the intervention group of 9 males (69.2%), and 4 females (30.8%), while the control group of 11 males (78.6%), and 3 females (21.4%); p = 0.678 Comorbidities have a significant influence on the decline of kidney function and the initial etiology of CKD. In this study, it was dominated by hypertension (85.2%), type 2 Diabetes mellitus (T2DM) (7.4%) and hypertension with T2DM (7.4%); p = 0.366 There was a difference in HD duration obtained in the intervention group and the control group which are HD samples underwent hemodialysis for 1-month 3 patients (11.1%), 2 months 7 patirnts (25.9%), 3 months 5 patients (18.5%), 4 months 2 patients (7.4%), and 5 months 6 patients (22.2%) and 6 months 4 patients (14.8%); p=0.041 From the employment data in the two groups dominated by enterpreneur 12 patients (44.4%), housewife/ non-working 6 patients (22.2%), retired civil servants 4 patients (14.8%), students 2 patients (7.4%), farmers 2 patients (7.4%), and soldier 1 patients (3.7%); p=0.420 Table 1. Patients’ characteristics Characteristic Intervention Control P-value (n=13) (n=14) Age (year-old) 49.62(13.14%) 41.57(13.22%) 0.126* Gender (n) 0.678* Male 9 (69.2%) 11(78.6%) Female 4(30.8%) 3(21.4%) Comorbidity 0.366* Hypertension 12 (92.3%) 11 (78.6%) Diabetes 1 (7.7%) 1 (7.1%) Hypertension and Diabetes 0 2 (14.3%) Hemodialysis Duration (Months) 0.041* 1 0 3 (21.4%) 2 3 (23.1%) 4 (28.6%) 3 4 (30.8%) 1 (7.1%) 4 2 (15.4%) 0 5 49 (30.8%) 2 (14.3%) 6 0 49 (28.6%) Occupation 0.420* Not working/Housewife 4 (30.8%) 2 (14.3%) Enterpreneur 5 (38.5%) 7 (50.0%) Retired civil servants 3(23.1%) 1 (7.1%) Student 0 2 (14.3%) Farmer 1(7.7%) 1 (7.1%) Soldier 0 1 (7.1)% Statistical analysis : * Mann Whitney Test Differences in Pre- and Post-Intervention Nutritional Status Anthropometric measurements in this study including Body Height, Body Weight, and Body Mass Index (BMI). Determination of nutritional status using BMI calculations and there was no significant difference between the two groups. Based on the assessment of nutritional status using BMI, most patients were at Normal BMI, determination of pre-post- intervention nutritional status in the intervention group (21.06±2.49 vs 21.32±2.24) p=0.331 and the control group (21.27±4.19 vs 21.12±4.18) p= 0.441 Table 2. Differences in Nutritional Status of Pre and Post Intervention Groups Intervention (n=13) Nilai p Control (n=14) P value Mean±SD Pre Mean±SD Post Mean±SD Pre Mean±SD Post Height (Cm) 161.38±7.25 161.38±7.25 - 162.93±8.64 162.93±8.64 - Weight (kg) 54.81±7.75 55.46±6.90 0.341* 56.36±10.52 56.04±10.49 0.348* BMI 21.06±2.49 21.32±2.24 0.331* 21.27±4.19 21.12±4.18 0.441** Note: n = number of subjects; BMI = Body Mass Index, Mean ± SD. Statistical analysis : * Paired t test: ** Wilcoxon test Food Composition, NLR and SCFA Pre and Post Intervention Table 3. Differences in Food Composition, NLR and SCFA Pre and Post Intervention of EVOO groups Groups Intervention (n=13) Nilai p Mean±SD Pre Mean±SD Post Energy (Kcal) 1042.33±311.17 1399.38±355.90 0.000* Protein (g) 43.44±18.87 47.03±16.44 0.223* Carbohydrates(g) 163.08±43.51 195.98±54.95 0.064* Fat (g) 23.56±14.46 47.25±12.36 0.000* NLR 5.07±7.35 2.74±2.18 0.007** Acetate 68.85±6.96 70.38±8.56 0.606* Propionate 16.77±4.55 15.31±5.60 0.498* Butyrate 6.77±3.52 8.00±4.10 0.470* Valerat 1.98±0.91 1.72±0.80 0.213* Absolute Butyrate 0.74±0.55 0.98±0.70 0.390* SCFA 8.31±3.77 8.92±3.88 0.670* Note: n = number of subjects; Kcal=kilocalori; g=gram ; NLR = Neutrophil-Lymphocyte Ratio , SCFA= short-chain fatty acids ,Mean ± SD. Statistical analysis : * Paired t test: ** Wilcoxon test In intervention group there was differences in pre and post intervention data on food composition, energy, and fat intake (p< 0.05) with additional EVOO consumed at a dose of 40 ml 4 times a day for 2 weeks. Table 3 showed, after 2 weeks of treatment a significant difference was obtained between pre and post variables of energy and fat (p< 0.05) There are significant differences in pre and post intervention on NLR 5.07±7.35 and 2.74±2.18 9 (p 0.670). Statistically, there was an increase in SCFA levels but there was no significant difference where the P value >0.05. Food Composition, NLR and SCFA Pre and Post Intervention of Control groups Table 4. Differences in Food Composition, NLR and SCFA Pre and Post Intervention of Control groups Groups Control (n=14) P value Mean±SD Pre Mean±SD Post Energy (Kcal) 1096.57±332.28 1017.95±323.78 0.287* Protein (g) 45.11±16.55 40.62±17.89 0.393* Carbohydrates(g) 171.84±61.09 168.01±49.24 0.768* Fat (g) 24.66±10.76 19.91±11.40 0.180* NLR 3.86±2.21 4.26±2.56 0.196** Acetate 71.07±8.22 70.07±7.33 0.598* Propionate 16.93±6.86 17.64±4.62 0.327** Butyrate 6.93±4.07 7.29±4.30 0.753** Valerat 1.31±0.66 1.32±0.56 0.933* Absolute Butyrate 1.10±0.92 1.21±0.88 0.648* SCFA 11.50±4.80 11.50±3.86 0.550** Note: n = number of subjects; Kcal=kilocalorie; g=gram ; NLR = Neutrophil-Lymphocyte Ratio , SCFA= short-chain fatty acids ; Mean ± SD. Statistical analysis : * Paired t test: ** Wilcoxon test In the control group of this study it was found that in the composition of food, energy, and fat intake there was a decrease in pre- and post-intervention data and from the results of statistical tests there was no significant difference. This is because there is no additional provision of EVOO for consumption, P>0.05 is obtained for Mean±SD Energy pre 1096.57±332.28 and Mean±SD post 1017.95±323.78 with a P value of 0.287 and Mean±SD pre Fat 24.66±10.76 and Mean±SD post 19.91±11.40 with a P value of 0.180. From measuring pre and post NLR variables, the results obtained are as follow Mean±SD pre 3.86±2.21 and post 19.91±11.40 with a P value of 0.05 after 2 weeks. While the results of measuring pre and post-intervention SCFA variables with Pro Healthy Gut examination, the statistical data obtained pre-intervention Mean±SD values of 11.50±4.80 and post-intervention 11.50±3.86 with P values of 0.550. There was a decrease in SCFA levels and from statistical test results there was no significant difference where P value >0.05. Discussion Research found that 31% of CKD patients suffer from protein-energy malnutrition (PEM), which can increase the risk of death up to five times if left untreated. Simple malnutrition refers to nutritional abnormalities caused by inadequate nutrient intake, while wasting caused by CKD refers to nutritional abnormalities that may be associated with inflammation and cannot be corrected simply by improving the diet. The International Society of Renal Nutrition and Metabolism (ISRNM) has proposed a general nomenclature and diagnostic criteria for this malnourished status in the context of CKD They suggest that the term protein-energy wasting (PEW) be used to describe the simultaneous loss of protein storage and energy in CKD patients. 17 The Neutrophil-Lymphocyte Ratio is a marker of chronic inflammation. These markers are obtained easily from the ratio between neutrophils and lymphocytes. Neutrophils are effector cells of the immune system, which increase in inflammation and produce increased oxidative stress. Specific lymphocyte subtypes, such as Th2 and T regulators, reduce inflammation through different pathways, such as GATA3 and FOXP3. Therefore, an increase in NLR reflects an imbalance of pro-inflammatory cytokines, as effector cells increase, and regulatory cells decrease. In CKD oxidative stress, increased pro-inflammatory cytokines (PCT, IL-6, TNF-α) and poor nutritional status caused by this imbalance contribute to the development of the disease. 18 Short Chain Fatty Acid exhibits large-scale physiological functions, including inhibition of histone deacetylases (HDAC), regulation of chemotaxis and phagocytosis, as well as induction of reactive oxygen species (ROS). Acetate, the most abundant SCFA in peripheral circulation, can cross the blood-brain barrier (BBB) and effectively weaken appetite by modulating the central nervous system. Butyrate is absorbed and used by colonic epithelial cells and is the preferred source of energy in colonic and cecum cells. 19 In this study, the basic data characteristics test showed that the length of HD was different between intervention and control group. Under normal conditions, inflammation is a protective and physiological response to various harmful stimuli. However, in some debilitating chronic disorders, such as CKD, the inflammation becomes maladaptive, uncontrollable, and persistent. Persistent systemic inflammation, for nearly 20 years, has been recognized as a major contributor to the uraemic phenotype (such as cardiovascular disease, protein energy wastage, depression, osteoporosis, and weakness), and a predictor of cardiovascular and total mortality. Since inflammation is mechanically linked to some aging process (inflammageing), it may be a major driver of the progeric phenotype in the uraemic environment. Inflammation is likely a consequence of multifactorial etiology and interacts with a number of factors that appear when uraemic toxins accumulate 15 . This may affect the characteristics of the basic data in this study. Differences in nutritional status, food composition, NLR and pre and post intervention SCFA levels in both groups In this study there was no difference in nutritional status before and after both in the Intervention group and the control group. Various mechanisms are involved in adverse nutritional changes in CKD patients. Poor dietary intake caused by uremia-induced anorexia alone does not explain adverse nutritional changes. There are additional contributing causes, such as persistent inflammation, acidosis, multiple hormonal disorders, comorbidities, and physical inactivity. Many studies on the nutritional status of CKD patients reveal that wastage and abnormalities of protein energy can be caused by inflammatory processes. Simple malnutrition refers to nutritional abnormalities caused by inadequate nutrient intake, while wasting caused by CKD refers to nutritional abnormalities that may be related to inflammation and cannot be corrected simply by improving diet. The International Society of Renal Nutrition and Metabolism (ISRNM) proposes a general nomenclature and diagnostic criteria for this malnutrition status in the context of CKD, Protein-energy wasting (PEW) is proposed to show concomitant loss in protein and energy storage in Chronic Kidney Disease patients. 17 In this study, there were differences in food composition in the Intervention group and the control group, especially the total fat of the food given. Among glyceride fractions, olive oil exhibits a high content of fatty acids and in particular high monounsaturated fatty acids (MUFAs). This olive oil compound has shown potential as an antioxidant, anti-inflammatory and antimicrobial agent. However, its concentration is related to various factors: olive variety, environmental factors, harvest and extraction time, as well as storage conditions this olive oil compound has shown potential as an antioxidant, anti-inflammatory and antimicrobial agent. 16 Our study showed significant differences were found in NLR levels in routine blood samples before and after administration of EVOO in the intervention group and control group. A recent meta-analysis of randomized controlled trials evaluated the effects of regular olive oil intake on inflammation. The authors reported reduced levels of IL-6, tumor necrosis factor-α (TNF-α) and CRP, which are the three indicators of plasma inflammation considered. Such beneficial effects were demonstrated in studies when EVOO was taken regularly for more than 3 months. The participants' overall health status should also be considered, as the strongest positive effects were reported among the unhealthy group (type 2 diabetes mellitus or at risk of CVD). Another meta-analysis of 3,106 participants also showed a significant reduction in IL-6 and CRP levels, when olive oil was consumed as an additional or natural intake. Adherence to high-phenol Virgin Olive Oil breakfast decreased postprandial inflammatory response, reducing plasma lipopolysaccharide levels in patients with metabolic syndrome. The higher polyphenol content of EVOO may mediate beneficial effects as anti-inflammatory effects have been demonstrated in vitro. Anti-inflammatory effects of EVOO-enriched phenolic compounds have also been reported in adipose tissue in rats, with anti-atherosclerotic effects. The higher polyphenol content of EVOO may mediate beneficial effects as anti-inflammatory effects have been demonstrated in vitro. Anti-inflammatory effects of EVOO-enriched phenolic compounds have also been reported in adipose tissue in rats, with anti-atherosclerotic effects. The higher polyphenol content of EVOO may mediate beneficial effects as anti-inflammatory effects have been demonstrated in vitro. Anti-inflammatory effects of EVOO-enriched phenolic compounds have also been reported in adipose tissue in rats, with anti-atherosclerotic effects. 20 , 21 Neutrophil-Lymphocyte Ratio has been included as a blood-based inflammatory biomarker because it can reflect a balance between innate (neutrophil) and adaptive (lymphocyte) immune responses. NLR increases based on the degree of obesity and indicates a high circulating neutrophil count, and in individuals with obesity, this can be considered an acute inflammatory response to a chronic inflammatory state. More recently, low-quality diets have been shown to be associated with higher inflammatory status as measured by NLR in older Spanish populations. With respect to CRP, a systematic review and meta-analysis of randomized controlled trials showed a notable decrease in CRP (SMD: -0.11.95% CI: -0.21, -0.01, p = 0.038) after oleic acid supplementation in adults and a minimum intervention duration of 4 weeks. 13 In this study, differences were found in the levels of SCFA in fecal samples before and after administration of EVOO in the Intervention group and control group where EVOO administration affected intestinal mucosal health and supported intestinal microbiota homeostasis by encouraging the production of intestinal immunoglobulin A (IgA), which was measured by enzyme-linked immunosorbent assay using fecal homogenate; dampens the production of inflammatory cytokines; supports the production and expression of cytokines and transcription factors involved in reducing inflammation and improving immune tolerance in the gut; and protects against intestinal oxidative injury through the potent antioxidant activity of EVOO phenolic extract. 22 , 23 Extra Virgin Olive Oil affects the gut microbiota by reducing the abundance of pathogenic bacteria, stimulating the growth of beneficial bacteria, and increasing the production of microbe-produced short-chain fatty acids (SCFAs), which exert various anti-inflammatory effects, and can modulate the expression of various genes through epigenetic mechanisms. 24 This explains why there were significant levels of SCFA differences in similar stools in this study. Several studies have shown that EVOO consumption increases Bacteroidetes and/or reduces the Firmicutes/Bacteroidetes ratio, both of which are associated with athero protection. EVOO also increases the diversity of beneficial bacteria and certain gut bacteria that can be therapeutic for lipid immune disorders and obesity. In addition, some of the mechanisms involved in the relationship between EVOO and this disorder include antimicrobial activity, microbial cholesterol metabolism, and metabolites produced by bacteria. Specifically, EVOO modulates short-chain fatty acids produced by the gut microbiota, which can affect cholesterol metabolism and the immune system, and may play a role in weight gain by increasing satiety. 25 Limitations The study had some limitations: the risk of over-reporting and memory bias in 24-hour food recall could not be ruled out. Conclusion From this study it can be concluded that there are differences in inflammatory markers in the research group. After 2 weeks of EVOO administration, NLR was found to decrease in the Intervention group while NLR increased in the control group. SCFA levels increased in the Intervention group and did not increase in the control group, but EVOO affected Short SCFA levels in the gastrointestinal tract. References Indonesian Ministry of Health. Basic Health Research Results (2018) Ministry of Health. RI 53, 1689–1699 (2018) Anothaisintawee T, Rattanasiri S, Ingsathit A, Attia J, Thakkinstian A (2009) Prevalence of chronic kidney disease: A systematic review and meta-analysis. Clin Nephrol 71:244–254 Pernefri (2016) 9th report of the Indonesian Society of Nephrology. Perkumpulan Nefrol Indones 1–46 Pahl MV, Vaziri, ND Immune Function in Chronic Kidney Disease (2015) Chronic Kidney Disease (Elsevier Inc. 10.1016/B978-0-12-411602-3.00024-X Cigarran S, González E, Cases A (2017) Gut microbiota in chronic kidney disease ଝ. 7:9–19 Abbas AK, Pillai, Shiv, Lichtman AH (2013) Basic immunology: functions and disorders of the immune system (4th). Basic immunology: functions and disorders of the immune system (4th)Elsevier Saunders Jayne E, Marshall (2007) Le couvent des Dominicaines de Notre-Dame de Nazareth, un site monastique à Aix-en-Provence. Analyse des données archéologiques et premiers éléments de topographie péri-urbaine médiévale. Sci (80-) 336:1268–1273 Dai L et al (2017) Clinical global assessment of nutritional status as a predictor of mortality in chronic kidney disease patients. PLoS ONE 12:1–17 Tonyali S, Ceylan C, Yahsi S, Karakan MS (2018) Does neutrophil and lymphocyte ratio indicate deterioration of kidney function? Ren Fail 40:209–212 Gokce MI et al (2016) Re: Neutrophil-tolymphocyte ratio in clinical practice. J Can Urol Assoc 10:142 Yoshitomi R et al (2019) High neutrophil/lymphocyte ratio is associated with poor renal outcome in Japanese patients with chronic kidney disease. Ren Fail 41:238–243 Rukavina Mikusic NL, Kouyoumdzian NM, Choi (2020) MR Gut microbiota and chronic kidney disease: evidence and mechanisms mediating novel communication in the gastrointestinal-renal axis. Pflugers arch. Eur J Physiol 472:303–320 Wang S et al (2019) Quantitative reduction of short-chain fatty acids, especially butyrate, contributes to the development of chronic kidney disease. Clin Sci 133:1857–1870 Rysz J, Franczyk B, Cialkowska-Rysz A (2017) Gluba-Brzózka, A. Effect of diet on survival of patients with chronic kidney disease. Nutrition 9:1–17 Noce A et al (2021) Usefulness of minor polar compounds of extra virgin olive oil in the management of chronic kidney disease patients. Nutrition 13:1–17 Jimenez-Lopez C et al (2020) Bioactive compounds and quality of extra virgin olive oil. Foods 9 Hyun YY et al (2017) Nutritional status in adults with predialysis chronic kidney disease: The KNOW-CKD study. J Korean Med Sci 32:257–263 Cobo G, Lindholm B, Stenvinkel P (2018) Chronic inflammation in end-stage renal disease and dialysis. Nephrol Dial Transpl 33:iii35–iii40 Marrone G et al (2022) Extra Virgin Olive Oil and Cardiovascular Protection in Chronic Kidney Disease. Nutrition 14:1–19 Luque-Sierra A, Alvarez-Amor L, Kleemann R, Martín F, Varela LM (2018) Extra Virgin Olive Oil with Natural Phenolic Content Exerts Anti-Inflammatory Effects on Adipose Tissue and Reduces the Severity of Atherosclerosis Lesions in Ldlr-/- Mice.Leiden. Mol. Nutr. Food Res 62:1–34 Moorthy M, Chaiyakunapruk N, Jacob SA, Palanisamy UD (2020) Prebiotic potential of polyphenols, their effects on gut microbiota and anthropometric/clinical markers: A systematic review of randomized controlled trials. Trends Food Sci Technol 99:634–649 Gavahian M et al (2019) Health benefits of olive oil and its components: Impact on antioxidant activity of gut microbiota, and prevention of non-communicable diseases. Trends Food Sci Technol 88:220–227 Diseases C, Microbiota G, Santana LF, Pott A, Donadon J (2019) R. E ff ects of Olive Oil and Its Minor Components on. 4–6 Incani A et al (2016) Extra virgin olive oil phenolic extracts counteract the pro-oxidant effect of dietary oxidized lipids in human intestinal cells. Food Chem Toxicol 90:171–180 Hernáez Á et al (2014) Olive oil polyphenols enhance high-density lipoprotein function in humans: A randomized controlled trial. Arterioscler Thromb Vasc Biol 34:2115–2119 Additional Declarations The authors declare no competing interests. Supplementary Files BismilahRawDataSamplebaselineHasilSCFACKD.xlsx 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-4576443","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":314056562,"identity":"0858a1a6-7218-4850-96c3-1d24b44d7f7a","order_by":0,"name":"Mely Marita MZ","email":"","orcid":"","institution":"Clinical Nutrition Medical Specialty Education Program, Faculty of Medicine, Hasanuddin University","correspondingAuthor":false,"prefix":"","firstName":"Mely","middleName":"Marita","lastName":"MZ","suffix":""},{"id":314056563,"identity":"0830f31c-760c-4ef4-820c-e8efb4e32da8","order_by":1,"name":"Haerani Rasyid","email":"","orcid":"","institution":"Department of Nutrition, Faculty of Medicine, Hasanuddin University","correspondingAuthor":false,"prefix":"","firstName":"Haerani","middleName":"","lastName":"Rasyid","suffix":""},{"id":314056564,"identity":"f2935ca6-22c3-48f4-b5d8-d738c8cb7ae9","order_by":2,"name":"Nurpudji Astuti Taslim","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4UlEQVRIiWNgGAWjYHACA4MEEMXO2MDwgYEhgVgtBgwMzIwNjDOI1QLBzEDEQ4wWc4nkDQUPGP7Iyzczt262bbPL42dvYPzwMQe3FssZaQUghxluOMzYdju3LblYsucAs+TMbXhcdSMH7BfGDcxgLcyJG24ksDHzEqHFfn4zUItlWz3xWhIbQA5jbDtMWItlzzOQX4yTQX652XPueOLMnoPNeP1izp68zfAHg5zt/Pb2Zzd+lFUn9rM3H/zwEZ/DGBjYDBj/QXmMbGCyAbd6iBbmBwjuH7yKR8EoGAWjYIQCAMgQUweC1w8cAAAAAElFTkSuQmCC","orcid":"","institution":"Department of Nutrition, Faculty of Medicine, Hasanuddin University","correspondingAuthor":true,"prefix":"","firstName":"Nurpudji","middleName":"Astuti","lastName":"Taslim","suffix":""},{"id":314056565,"identity":"dfdc99fa-a1fb-4e3e-b216-6ba1a9ad5895","order_by":3,"name":"Suryani As’ad","email":"","orcid":"","institution":"Department of Nutrition, Faculty of Medicine, Hasanuddin University","correspondingAuthor":false,"prefix":"","firstName":"Suryani","middleName":"","lastName":"As’ad","suffix":""},{"id":314056566,"identity":"1cba8998-9522-4117-9b7d-f7f8b7722b08","order_by":4,"name":"Agussalim Bukhari","email":"","orcid":"","institution":"Department of Nutrition, Faculty of Medicine, Hasanuddin University","correspondingAuthor":false,"prefix":"","firstName":"Agussalim","middleName":"","lastName":"Bukhari","suffix":""},{"id":314056567,"identity":"2ca07216-da02-4734-b878-3826f5684db3","order_by":5,"name":"Aminuddin","email":"","orcid":"","institution":"Department of Nutrition, Faculty of Medicine, Hasanuddin University","correspondingAuthor":false,"prefix":"","firstName":"","middleName":"","lastName":"Aminuddin","suffix":""},{"id":314056568,"identity":"1d9632cc-b0c3-479a-b71d-c60eae0bc4f4","order_by":6,"name":"Andi Yasmin Syauki","email":"","orcid":"","institution":"Department of Nutrition, Faculty of Medicine, Hasanuddin University","correspondingAuthor":false,"prefix":"","firstName":"Andi","middleName":"Yasmin","lastName":"Syauki","suffix":""},{"id":314056569,"identity":"39db2284-51ca-491b-9640-fe8d13ed6342","order_by":7,"name":"Mardiana Madjid","email":"","orcid":"","institution":"Department of Nutrition, Faculty of Medicine, Hasanuddin University","correspondingAuthor":false,"prefix":"","firstName":"Mardiana","middleName":"","lastName":"Madjid","suffix":""}],"badges":[],"createdAt":"2024-06-13 13:17:53","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-4576443/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4576443/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":59186229,"identity":"03674e36-c5fe-4483-90b9-a44d3b35fa9b","added_by":"auto","created_at":"2024-06-27 12:05:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":519000,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4576443/v1/79c8c4c0-b40a-46e7-bc46-df80eceba6d7.pdf"},{"id":59185873,"identity":"82e5e350-246c-4e5b-a57d-0f26d2904c15","added_by":"auto","created_at":"2024-06-27 11:57:48","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":38219,"visible":true,"origin":"","legend":"","description":"","filename":"BismilahRawDataSamplebaselineHasilSCFACKD.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-4576443/v1/c743fbdfb879fd14bab16480.xlsx"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eVirgin Olive Oil Extract as anti-inflammatory on Patients with Chronic Kidney Disease: Analysis of Neutrophil-to-lymphocyte Ratio and Short-Chain Fatty Acid\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe prevalence and incidence of CKD increased with increasing incidence of diabetes mellitus and hypertension. The condition can develop into kidney failure which is a world health problem due to a poor prognosis and high cost.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e A meta-analysis and systematic review study showed a world prevalence of CKD of 13.4%\u003csup\u003e2\u003c/sup\u003e and in Indonesia the number of new CKD patients increases each year, the incidence of new CKD in Indonesia until 2016 was 25,446 patients, with active patients 52,835.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e Financing for CKD treatment in Indonesia is ranked second after heart disease\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e (BPJS).\u003c/p\u003e \u003cp\u003eChronic Kidney Disease is associated with immune activation characterized by systemic inflammation and immunodeficiency.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e The composition and metabolic activity of microbiota changes in CKD due to quantitative and qualitative changes in the gut microbiota which started from the initial stage of CKD.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eChronic Kidney Disease patients are prone to be malnourished hence results in weight loss and immune system deficiency. Partly due to diet in low protein, sodium, vitamins, and water.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e The human immune system plays an important role in maintaining homeostasis with the microbiota, thus ensuring that the mutualism relationship with the host can be maintained. At the same time, the microbiota plays role in the human immune system. Therefore, a new paradigm postulates that the immune system has evolved to accommodate the colonization of an increasingly complex symbiotic microbiota while still retaining the capacity to resist pathogens. How colonies of bacteria from the gut can influence the development and functioning of the immune system become interesting topic to explore.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eVarious strategies have been developed by nephrologists to slow the progressivity of CKD. Nutrition management in CKD aims to improve quality of life, reduce morbidity and mortality and slow the progressivity of kidney disease. It is recommended that CKD patients need to modify their nutritional intake. Malnutrition conditions are often found in patients with CKD and other chronic diseases. This is due to various factors, such as impaired protein and energy metabolism, micronutrient deficiencies, hormonal dysregulation, infections, anorexia, inadequate intake, and uremic syndrome. Research states that 31% of CKD patients experience protein-energy malnutrition (PEM), where severe PEM can increase the risk of death up to 5 times.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eNeutrophil-Lymphocyte Ratio is a widely used systemic inflammatory biomarker, which can be obtained easily from a complete blood test.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e NLR is measured by dividing the number of neutrophils by the number of lymphocytes.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e Studies by Yoshitomi \u003cem\u003eet al.\u003c/em\u003e, have identified NLR levels as an independent risk factor for kidney disease progression in patients with stage 1\u0026ndash;4 CKD Thus, NLR measurements may be useful for predicting the progression of kidney disease in CKD patients.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eIt has been proven that the number of Short Chain Fatty Acid (SCFA)-producing bacteria is reduced in patients with CKD. Clinical studies investigating the potential measurement of circulating SCFA as a biological marker in diagnosis, prognosis, and therapeutic monitoring in renal patients are still rare.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e Wang \u003cem\u003eet al\u003c/em\u003e. showed that the main SCFAs (acetate, propionate, and butyrate) and especially butyrate were reduced in the patient's feces and serum during the development of CKD.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eIn the early stages of CKD, a \"healthy diet\" is recommended and is characterized by a high intake of vegetables, fruit, nuts, seeds, legumes, and fish, as well as a low intake of saturated fats and sodium.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e The Mediterranean diet represents a nutritional dietary regimen appropriate for the initial management of CKD. Among the typical products of the Mediterranean diet, the main food is represented by EVOO which is the main source of vegetable fats.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e EVOO consists mainly of triglycerides (97\u0026ndash;99%) and minor compounds (1\u0026ndash;3%).\u003csup\u003e16\u003c/sup\u003e Minor compounds, particularly phenolic are important for the health effects provided by EVOO.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e Many of the health benefits of a mediterranean diet enriched with EVOO have been reported such as protecting against cardiovascular disease, antioxidant properties, anti-inflammatory, antitumor activity, and modulation of the gut microbiota.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn Chronic Kidney Disease, several conditions such as malnutrition and decreased body resistance are often encountered. In this study, an intervention will be carried out in the form of giving EVOO and seeing whether EVOO administration affects inflammation and intestinal microbiota of CKD patients.\u003c/p\u003e"},{"header":"Method","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eResearch design\u003c/h2\u003e \u003cp\u003eThis study used a randomized clinical trial, pre post test design. About 30 participants were taken from CKD patients undergoing HD who had met the inclusion criteria.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eInclusion and Exclusion Criteria\u003c/h2\u003e \u003cp\u003eThe inclusion criteria of study: Patients able to communicate well, understand and give written consent to participate in the study, aged\u0026thinsp;\u0026gt;\u0026thinsp;18\u0026ndash;65 years, patients with a diagnosis of CKD undergo routine HD less than or equal to 3 comorbidities. The exclusion criteria: Patients who are not eligible for examination, patients consuming yogurt probiotics in the last 3 months, patients with symptoms and gastrointestinal disorders (diarrhea, vomiting, IBD and gastrointestinal bleeding).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eResearch Procedure\u003c/h2\u003e \u003cp\u003eThe samples of 15 participants in the intervention group given daily EVOO 40 ml for 2 weeks, and 15 participants were included in the control group without being given EVOO (only nutritional education), 3 samples was drop out (2 intervention and 1 control ) due to the patient could not continue the procedures (did not check blood and feces on the 2nd examination). Data collection is carried out in two stages. First, screening was carried out to collected samples, then determined samples that met the inclusion and exclusion criteria, second, followed by pre-intervention and intervention examinations for 2 weeks followed by post-intervention examinations stages one and two, namely the data collected including data from all variables taken in the study.\u003c/p\u003e \u003cp\u003eIn both groups, routine blood tests for NLR and intestinal microbiota (SCFA concentration in feces) were carried out, which are the end products of volatile gastrointestinal bacterial fermentation (acetate, propionate and butyrate which have an important role in gastrointestinal health) using Pro Healthy Gut examination.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe data obtained is processed and analyzed statistically using SPSS 25 for Windows and the results are displayed in the form of narratives, tables or graphs. The confidence level is 95% and is considered meaningful when p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. To compare numerical data using two categories or between groups using independent t test if data is normal, Mann-Whitney test used if data is abnormal. To compare numerical data in repeated measurements, observational measurements twice (pre post) use a t-paired test if the data is normal, and the Wilcoxon test used if the data is abnormal.\u003c/p\u003e \u003c/div\u003e"},{"header":"Result","content":"\u003cp\u003e\u003cstrong\u003eGeneral Overview of Research Samples\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was conducted at Dr. Wahidin Sudirohusodo Hospital Makassar after obtaining ethical approval from the Health Research Ethics Committee of the Faculty of Medicine, Hasanuddin University number: 580 / UN4.6.4.5.31 / PP36 / 2022 and received permission from the hospital. This study aims to determine whether there is an effect of EVOO on NLR and SCFA inflammation markers in CKD patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResearch Subjects\u0026rsquo; Characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study involved 30 patients with CKD undergoing HD who had met the inclusion criteria. The characteristics are as follows (table 1):\u0026nbsp;\u003c/p\u003e\n\u003col class=\"decimal_type\"\u003e\n \u003cli\u003eMean age value in the intervention group is 49.62 year-old (13.14%) compared to the median control group age 41.57 year-old (13.22%)\u003c/li\u003e\n \u003cli\u003eThe gender were dominated by males; 20 males (74.1%) and 7 females (25.9%), with comparisons between the intervention group of 9 males (69.2%), and 4 females (30.8%), while the control group of 11 males (78.6%), and 3 females (21.4%); p = 0.678\u003c/li\u003e\n \u003cli\u003eComorbidities have a significant influence on the decline of kidney function and the initial etiology of\u0026nbsp;CKD. In this study, it was dominated by hypertension (85.2%), type 2 Diabetes mellitus (T2DM) (7.4%) and hypertension with T2DM (7.4%); p = 0.366\u003c/li\u003e\n \u003cli\u003eThere was a difference in HD duration\u0026nbsp;obtained in the intervention group and the control group which are HD samples underwent hemodialysis for 1-month 3 patients (11.1%), 2 months 7 patirnts (25.9%), 3 months 5 patients (18.5%), 4 months 2 patients (7.4%), and 5 months 6 patients (22.2%) and 6 months 4 patients (14.8%); p=0.041\u003c/li\u003e\n \u003cli\u003eFrom the employment data in the two groups dominated by enterpreneur 12 patients (44.4%), housewife/ non-working 6 patients (22.2%), retired civil servants 4 patients (14.8%), students 2 patients (7.4%), farmers 2 patients (7.4%), and soldier 1 patients (3.7%); p=0.420\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eTable 1. \u0026nbsp;Patients\u0026rsquo; characteristics\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"466\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.987124463519315%\" rowspan=\"2\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.107296137339056%\"\u003e\n \u003cp\u003eIntervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.17167381974249%\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.733905579399142%\" rowspan=\"2\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"55.45023696682465%\"\u003e\n \u003cp\u003e(n=13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"44.54976303317535%\"\u003e\n \u003cp\u003e(n=14)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.987124463519315%\"\u003e\n \u003cp\u003eAge (year-old)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.107296137339056%\"\u003e\n \u003cp\u003e49.62(13.14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.17167381974249%\"\u003e\n \u003cp\u003e41.57(13.22%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.733905579399142%\"\u003e\n \u003cp\u003e0.126*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.987124463519315%\"\u003e\n \u003cp\u003eGender (n)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.107296137339056%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"20.17167381974249%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"13.733905579399142%\"\u003e\n \u003cp\u003e0.678*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.987124463519315%\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.107296137339056%\"\u003e\n \u003cp\u003e9 (69.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.17167381974249%\"\u003e\n \u003cp\u003e11(78.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.733905579399142%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.987124463519315%\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.107296137339056%\"\u003e\n \u003cp\u003e4(30.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.17167381974249%\"\u003e\n \u003cp\u003e3(21.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.733905579399142%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.987124463519315%\"\u003e\n \u003cp\u003eComorbidity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.107296137339056%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"20.17167381974249%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"13.733905579399142%\"\u003e\n \u003cp\u003e0.366*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.987124463519315%\"\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.107296137339056%\"\u003e\n \u003cp\u003e12 (92.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.17167381974249%\"\u003e\n \u003cp\u003e11 (78.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.733905579399142%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.987124463519315%\"\u003e\n \u003cp\u003eDiabetes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.107296137339056%\"\u003e\n \u003cp\u003e1 (7.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.17167381974249%\"\u003e\n \u003cp\u003e1 (7.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.733905579399142%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.987124463519315%\"\u003e\n \u003cp\u003eHypertension and Diabetes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.107296137339056%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.17167381974249%\"\u003e\n \u003cp\u003e2 (14.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.733905579399142%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.987124463519315%\"\u003e\n \u003cp\u003eHemodialysis Duration (Months)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.107296137339056%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"20.17167381974249%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"13.733905579399142%\"\u003e\n \u003cp\u003e0.041*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.987124463519315%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.107296137339056%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.17167381974249%\"\u003e\n \u003cp\u003e3 (21.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.733905579399142%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.987124463519315%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.107296137339056%\"\u003e\n \u003cp\u003e3 (23.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.17167381974249%\"\u003e\n \u003cp\u003e4 (28.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.733905579399142%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.987124463519315%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.107296137339056%\"\u003e\n \u003cp\u003e4 (30.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.17167381974249%\"\u003e\n \u003cp\u003e1 (7.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.733905579399142%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.987124463519315%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.107296137339056%\"\u003e\n \u003cp\u003e2 (15.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.17167381974249%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.733905579399142%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.987124463519315%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.107296137339056%\"\u003e\n \u003cp\u003e49 (30.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.17167381974249%\"\u003e\n \u003cp\u003e2 (14.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.733905579399142%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.987124463519315%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.107296137339056%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.17167381974249%\"\u003e\n \u003cp\u003e49 (28.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.733905579399142%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.987124463519315%\"\u003e\n \u003cp\u003eOccupation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.107296137339056%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"20.17167381974249%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"13.733905579399142%\"\u003e\n \u003cp\u003e0.420*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.987124463519315%\"\u003e\n \u003cp\u003eNot working/Housewife\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.107296137339056%\"\u003e\n \u003cp\u003e4 (30.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.17167381974249%\"\u003e\n \u003cp\u003e2 (14.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.733905579399142%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.987124463519315%\"\u003e\n \u003cp\u003eEnterpreneur\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.107296137339056%\"\u003e\n \u003cp\u003e5 (38.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.17167381974249%\"\u003e\n \u003cp\u003e7 (50.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.733905579399142%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.987124463519315%\"\u003e\n \u003cp\u003eRetired civil servants\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.107296137339056%\"\u003e\n \u003cp\u003e3(23.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.17167381974249%\"\u003e\n \u003cp\u003e1 (7.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.733905579399142%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.987124463519315%\"\u003e\n \u003cp\u003eStudent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.107296137339056%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.17167381974249%\"\u003e\n \u003cp\u003e2 (14.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.733905579399142%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.987124463519315%\"\u003e\n \u003cp\u003eFarmer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.107296137339056%\"\u003e\n \u003cp\u003e1(7.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.17167381974249%\"\u003e\n \u003cp\u003e1 (7.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.733905579399142%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.987124463519315%\"\u003e\n \u003cp\u003eSoldier\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.107296137339056%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.17167381974249%\"\u003e\n \u003cp\u003e1 (7.1)%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.733905579399142%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eStatistical analysis : * Mann Whitney Test\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDifferences in Pre- and Post-Intervention Nutritional Status\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAnthropometric measurements in this study including Body Height, Body Weight, and Body Mass Index (BMI). Determination of nutritional status using BMI calculations and there was no significant difference between the two groups. Based on the assessment of nutritional status using BMI, most patients were at Normal BMI, determination of pre-post- intervention nutritional status in the intervention group (21.06\u0026plusmn;2.49 vs 21.32\u0026plusmn;2.24) p=0.331 and \u0026nbsp;the control group (21.27\u0026plusmn;4.19 vs 21.12\u0026plusmn;4.18) p= 0.441\u003c/p\u003e\n\u003cp\u003eTable 2. Differences in Nutritional Status of Pre and Post Intervention\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"600\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.190317195325543%\" rowspan=\"2\"\u003e\n \u003cp\u003eGroups\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.719532554257096%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eIntervention (n=13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.684474123539232%\" rowspan=\"2\"\u003e\n \u003cp\u003eNilai p\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.3873121869783%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eControl (n=14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.018363939899833%\" rowspan=\"2\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.739583333333332%\" valign=\"bottom\"\u003e\n \u003cp\u003eMean\u0026plusmn;SD Pre\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.739583333333332%\" valign=\"bottom\"\u003e\n \u003cp\u003eMean\u0026plusmn;SD Post\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.739583333333332%\" valign=\"bottom\"\u003e\n \u003cp\u003eMean\u0026plusmn;SD Pre\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.78125%\" valign=\"bottom\"\u003e\n \u003cp\u003eMean\u0026plusmn;SD Post\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.190317195325543%\" valign=\"top\"\u003e\n \u003cp\u003eHeight (Cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.859766277128548%\"\u003e\n \u003cp\u003e161.38\u0026plusmn;7.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.859766277128548%\"\u003e\n \u003cp\u003e161.38\u0026plusmn;7.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.684474123539232%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.859766277128548%\"\u003e\n \u003cp\u003e162.93\u0026plusmn;8.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.52754590984975%\"\u003e\n \u003cp\u003e162.93\u0026plusmn;8.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.018363939899833%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.190317195325543%\" valign=\"top\"\u003e\n \u003cp\u003eWeight (kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.859766277128548%\"\u003e\n \u003cp\u003e54.81\u0026plusmn;7.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.859766277128548%\"\u003e\n \u003cp\u003e55.46\u0026plusmn;6.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.684474123539232%\"\u003e\n \u003cp\u003e0.341*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.859766277128548%\"\u003e\n \u003cp\u003e56.36\u0026plusmn;10.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.52754590984975%\"\u003e\n \u003cp\u003e56.04\u0026plusmn;10.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.018363939899833%\"\u003e\n \u003cp\u003e0.348*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.190317195325543%\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.859766277128548%\"\u003e\n \u003cp\u003e21.06\u0026plusmn;2.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.859766277128548%\"\u003e\n \u003cp\u003e21.32\u0026plusmn;2.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.684474123539232%\"\u003e\n \u003cp\u003e0.331*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.859766277128548%\"\u003e\n \u003cp\u003e21.27\u0026plusmn;4.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.52754590984975%\"\u003e\n \u003cp\u003e21.12\u0026plusmn;4.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.018363939899833%\"\u003e\n \u003cp\u003e0.441**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNote: n = number of subjects; BMI = Body Mass Index, Mean \u0026plusmn; SD. Statistical analysis : * Paired t test: ** Wilcoxon test\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFood Composition, NLR and SCFA Pre and Post Intervention\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 3. Differences in Food Composition, NLR and SCFA Pre and Post Intervention of EVOO groups\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"431\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.302325581395348%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eGroups\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"55.348837209302324%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eIntervention \u0026nbsp; \u0026nbsp; (n=13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.348837209302326%\" rowspan=\"2\"\u003e\n \u003cp\u003eNilai p\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"bottom\"\u003e\n \u003cp\u003eMean\u0026plusmn;SD Pre\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"bottom\"\u003e\n \u003cp\u003eMean\u0026plusmn;SD Post\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.302325581395348%\" valign=\"top\"\u003e\n \u003cp\u003eEnergy (Kcal)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.674418604651162%\"\u003e\n \u003cp\u003e1042.33\u0026plusmn;311.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.674418604651162%\"\u003e\n \u003cp\u003e1399.38\u0026plusmn;355.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.348837209302326%\"\u003e\n \u003cp\u003e0.000*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.302325581395348%\" valign=\"top\"\u003e\n \u003cp\u003eProtein (g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.674418604651162%\"\u003e\n \u003cp\u003e43.44\u0026plusmn;18.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.674418604651162%\"\u003e\n \u003cp\u003e47.03\u0026plusmn;16.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.348837209302326%\"\u003e\n \u003cp\u003e0.223*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.302325581395348%\" valign=\"top\"\u003e\n \u003cp\u003eCarbohydrates(g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.674418604651162%\"\u003e\n \u003cp\u003e163.08\u0026plusmn;43.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.674418604651162%\"\u003e\n \u003cp\u003e195.98\u0026plusmn;54.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.348837209302326%\"\u003e\n \u003cp\u003e0.064*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.302325581395348%\" valign=\"top\"\u003e\n \u003cp\u003eFat (g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.674418604651162%\"\u003e\n \u003cp\u003e23.56\u0026plusmn;14.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.674418604651162%\"\u003e\n \u003cp\u003e47.25\u0026plusmn;12.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.348837209302326%\"\u003e\n \u003cp\u003e0.000*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.302325581395348%\"\u003e\n \u003cp\u003eNLR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.674418604651162%\"\u003e\n \u003cp\u003e5.07\u0026plusmn;7.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.674418604651162%\"\u003e\n \u003cp\u003e2.74\u0026plusmn;2.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.348837209302326%\"\u003e\n \u003cp\u003e0.007**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.302325581395348%\" valign=\"top\"\u003e\n \u003cp\u003eAcetate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.674418604651162%\"\u003e\n \u003cp\u003e68.85\u0026plusmn;6.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.674418604651162%\"\u003e\n \u003cp\u003e70.38\u0026plusmn;8.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.348837209302326%\"\u003e\n \u003cp\u003e0.606*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.302325581395348%\" valign=\"top\"\u003e\n \u003cp\u003ePropionate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.674418604651162%\"\u003e\n \u003cp\u003e16.77\u0026plusmn;4.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.674418604651162%\"\u003e\n \u003cp\u003e15.31\u0026plusmn;5.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.348837209302326%\"\u003e\n \u003cp\u003e0.498*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.302325581395348%\" valign=\"top\"\u003e\n \u003cp\u003eButyrate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.674418604651162%\"\u003e\n \u003cp\u003e6.77\u0026plusmn;3.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.674418604651162%\"\u003e\n \u003cp\u003e8.00\u0026plusmn;4.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.348837209302326%\"\u003e\n \u003cp\u003e0.470*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.302325581395348%\" valign=\"top\"\u003e\n \u003cp\u003eValerat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.674418604651162%\"\u003e\n \u003cp\u003e1.98\u0026plusmn;0.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.674418604651162%\"\u003e\n \u003cp\u003e1.72\u0026plusmn;0.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.348837209302326%\"\u003e\n \u003cp\u003e0.213*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.302325581395348%\" valign=\"top\"\u003e\n \u003cp\u003eAbsolute Butyrate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.674418604651162%\"\u003e\n \u003cp\u003e0.74\u0026plusmn;0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.674418604651162%\"\u003e\n \u003cp\u003e0.98\u0026plusmn;0.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.348837209302326%\"\u003e\n \u003cp\u003e0.390*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.302325581395348%\" valign=\"top\"\u003e\n \u003cp\u003eSCFA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.674418604651162%\"\u003e\n \u003cp\u003e8.31\u0026plusmn;3.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.674418604651162%\"\u003e\n \u003cp\u003e8.92\u0026plusmn;3.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.348837209302326%\"\u003e\n \u003cp\u003e0.670*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNote: n = number of subjects; Kcal=kilocalori; g=gram ; NLR = \u003cem\u003eNeutrophil-Lymphocyte Ratio\u003c/em\u003e, SCFA= \u003cem\u003eshort-chain fatty acids\u003c/em\u003e,Mean \u0026plusmn; SD. Statistical analysis : * Paired t test: ** Wilcoxon test\u003c/p\u003e\n\u003cp\u003eIn intervention group there was differences in pre and post intervention data on food composition, energy, and fat intake (p\u0026lt; 0.05) with additional EVOO consumed at a dose of 40 ml 4 times a day for 2 weeks. \u0026nbsp;Table 3 showed, after 2 weeks of treatment a significant difference was obtained between pre and post variables of energy and fat (p\u0026lt; 0.05)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere are significant differences in pre and post intervention on NLR \u0026nbsp;5.07\u0026plusmn;7.35 and 2.74\u0026plusmn;2.18 9 (p \u0026lt;0.007), while for SCFA measurements not significant 8.31\u0026plusmn;3.77 and post 8.92\u0026plusmn;3.88 (p\u0026gt;0.670). \u0026nbsp; Statistically, there was an increase in SCFA levels but there was no significant difference where the P value \u0026gt;0.05.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFood Composition,\u003c/strong\u003e \u003cstrong\u003eNLR\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;and SCFA Pre and Post Intervention of Control groups\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 4. Differences in Food Composition, NLR and SCFA Pre and Post Intervention of Control groups\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"551\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.76086956521739%\" rowspan=\"2\"\u003e\n \u003cp\u003eGroups\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"47.10144927536232%\" colspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003eControl (n=14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.13768115942029%\" rowspan=\"2\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"bottom\"\u003e\n \u003cp\u003eMean\u0026plusmn;SD Pre\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"bottom\"\u003e\n \u003cp\u003eMean\u0026plusmn;SD Post\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.76086956521739%\" valign=\"top\"\u003e\n \u003cp\u003eEnergy (Kcal)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.55072463768116%\"\u003e\n \u003cp\u003e1096.57\u0026plusmn;332.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.55072463768116%\"\u003e\n \u003cp\u003e1017.95\u0026plusmn;323.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.13768115942029%\"\u003e\n \u003cp\u003e0.287*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.76086956521739%\" valign=\"top\"\u003e\n \u003cp\u003eProtein (g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.55072463768116%\"\u003e\n \u003cp\u003e45.11\u0026plusmn;16.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.55072463768116%\"\u003e\n \u003cp\u003e40.62\u0026plusmn;17.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.13768115942029%\"\u003e\n \u003cp\u003e0.393*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.76086956521739%\" valign=\"top\"\u003e\n \u003cp\u003eCarbohydrates(g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.55072463768116%\"\u003e\n \u003cp\u003e171.84\u0026plusmn;61.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.55072463768116%\"\u003e\n \u003cp\u003e168.01\u0026plusmn;49.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.13768115942029%\"\u003e\n \u003cp\u003e0.768*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.76086956521739%\" valign=\"top\"\u003e\n \u003cp\u003eFat (g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.55072463768116%\"\u003e\n \u003cp\u003e24.66\u0026plusmn;10.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.55072463768116%\"\u003e\n \u003cp\u003e19.91\u0026plusmn;11.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.13768115942029%\"\u003e\n \u003cp\u003e0.180*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.76086956521739%\"\u003e\n \u003cp\u003eNLR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.55072463768116%\"\u003e\n \u003cp\u003e3.86\u0026plusmn;2.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.55072463768116%\"\u003e\n \u003cp\u003e4.26\u0026plusmn;2.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.13768115942029%\"\u003e\n \u003cp\u003e0.196**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.76086956521739%\" valign=\"top\"\u003e\n \u003cp\u003eAcetate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.55072463768116%\" valign=\"top\"\u003e\n \u003cp\u003e71.07\u0026plusmn;8.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.55072463768116%\" valign=\"top\"\u003e\n \u003cp\u003e70.07\u0026plusmn;7.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.13768115942029%\" valign=\"top\"\u003e\n \u003cp\u003e0.598*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.76086956521739%\" valign=\"top\"\u003e\n \u003cp\u003ePropionate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.55072463768116%\" valign=\"top\"\u003e\n \u003cp\u003e16.93\u0026plusmn;6.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.55072463768116%\" valign=\"top\"\u003e\n \u003cp\u003e17.64\u0026plusmn;4.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.13768115942029%\" valign=\"top\"\u003e\n \u003cp\u003e0.327**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.76086956521739%\" valign=\"top\"\u003e\n \u003cp\u003eButyrate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.55072463768116%\" valign=\"top\"\u003e\n \u003cp\u003e6.93\u0026plusmn;4.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.55072463768116%\" valign=\"top\"\u003e\n \u003cp\u003e7.29\u0026plusmn;4.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.13768115942029%\" valign=\"top\"\u003e\n \u003cp\u003e0.753**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.76086956521739%\" valign=\"top\"\u003e\n \u003cp\u003eValerat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.55072463768116%\" valign=\"top\"\u003e\n \u003cp\u003e1.31\u0026plusmn;0.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.55072463768116%\" valign=\"top\"\u003e\n \u003cp\u003e1.32\u0026plusmn;0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.13768115942029%\" valign=\"top\"\u003e\n \u003cp\u003e0.933*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.76086956521739%\" valign=\"top\"\u003e\n \u003cp\u003eAbsolute Butyrate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.55072463768116%\" valign=\"top\"\u003e\n \u003cp\u003e1.10\u0026plusmn;0.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.55072463768116%\" valign=\"top\"\u003e\n \u003cp\u003e1.21\u0026plusmn;0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.13768115942029%\" valign=\"top\"\u003e\n \u003cp\u003e0.648*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.76086956521739%\" valign=\"top\"\u003e\n \u003cp\u003eSCFA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.55072463768116%\" valign=\"top\"\u003e\n \u003cp\u003e11.50\u0026plusmn;4.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.55072463768116%\" valign=\"top\"\u003e\n \u003cp\u003e11.50\u0026plusmn;3.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.13768115942029%\" valign=\"top\"\u003e\n \u003cp\u003e0.550**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNote: n = number of subjects; Kcal=kilocalorie; g=gram ; NLR = \u003cem\u003eNeutrophil-Lymphocyte Ratio\u003c/em\u003e, SCFA= \u003cem\u003eshort-chain fatty acids\u003c/em\u003e; Mean \u0026plusmn; SD. Statistical analysis : * Paired t test: ** Wilcoxon test\u003c/p\u003e\n\u003cp\u003eIn the control group of this study it was found that in the composition of food, energy, and fat intake there was a decrease in pre- and post-intervention data and from the results of statistical tests there was no significant difference. This is because there is no additional provision of EVOO for consumption, P\u0026gt;0.05 is obtained for Mean\u0026plusmn;SD Energy pre 1096.57\u0026plusmn;332.28 \u0026nbsp; and Mean\u0026plusmn;SD post 1017.95\u0026plusmn;323.78 \u0026nbsp; with a P value of 0.287 and Mean\u0026plusmn;SD pre Fat 24.66\u0026plusmn;10.76 and Mean\u0026plusmn;SD post 19.91\u0026plusmn;11.40 with a P value of 0.180.\u003c/p\u003e\n\u003cp\u003eFrom measuring pre and post NLR variables, the results obtained are as follow Mean\u0026plusmn;SD pre 3.86\u0026plusmn;2.21 and post 19.91\u0026plusmn;11.40 with a P value of \u0026lt;0.196. There was an increase in the NLR value in the control group and from statistical tests (Wilcoxon test) there was no significant difference where the NLR ratio value with P value \u0026gt;0.05 after 2 weeks. While the results of measuring pre and post-intervention SCFA variables with Pro Healthy Gut examination, the statistical data obtained pre-intervention Mean\u0026plusmn;SD values of 11.50\u0026plusmn;4.80 and post-intervention 11.50\u0026plusmn;3.86 with P values of 0.550. \u0026nbsp;There was a decrease in SCFA levels and from statistical test results there was no significant difference where P value \u0026gt;0.05. \u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eResearch found that 31% of CKD patients suffer from protein-energy malnutrition (PEM), which can increase the risk of death up to five times if left untreated. Simple malnutrition refers to nutritional abnormalities caused by inadequate nutrient intake, while wasting caused by CKD refers to nutritional abnormalities that may be associated with inflammation and cannot be corrected simply by improving the diet. The International Society of Renal Nutrition and Metabolism (ISRNM) has proposed a general nomenclature and diagnostic criteria for this malnourished status in the context of CKD They suggest that the term protein-energy wasting (PEW) be used to describe the simultaneous loss of protein storage and energy in CKD patients.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe Neutrophil-Lymphocyte Ratio is a marker of chronic inflammation. These markers are obtained easily from the ratio between neutrophils and lymphocytes. Neutrophils are effector cells of the immune system, which increase in inflammation and produce increased oxidative stress. Specific lymphocyte subtypes, such as Th2 and T regulators, reduce inflammation through different pathways, such as GATA3 and FOXP3. Therefore, an increase in NLR reflects an imbalance of pro-inflammatory cytokines, as effector cells increase, and regulatory cells decrease. In CKD oxidative stress, increased pro-inflammatory cytokines (PCT, IL-6, TNF-α) and poor nutritional status caused by this imbalance contribute to the development of the disease.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eShort Chain Fatty Acid exhibits large-scale physiological functions, including inhibition of histone deacetylases (HDAC), regulation of chemotaxis and phagocytosis, as well as induction of reactive oxygen species (ROS). Acetate, the most abundant SCFA in peripheral circulation, can cross the blood-brain barrier (BBB) and effectively weaken appetite by modulating the central nervous system. Butyrate is absorbed and used by colonic epithelial cells and is the preferred source of energy in colonic and cecum cells.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn this study, the basic data characteristics test showed that the length of HD was different between intervention and control group. Under normal conditions, inflammation is a protective and physiological response to various harmful stimuli. However, in some debilitating chronic disorders, such as CKD, the inflammation becomes maladaptive, uncontrollable, and persistent. Persistent systemic inflammation, for nearly 20 years, has been recognized as a major contributor to the uraemic phenotype (such as cardiovascular disease, protein energy wastage, depression, osteoporosis, and weakness), and a predictor of cardiovascular and total mortality. Since inflammation is mechanically linked to some aging process (inflammageing), it may be a major driver of the progeric phenotype in the uraemic environment. Inflammation is likely a consequence of multifactorial etiology and interacts with a number of factors that appear when uraemic toxins accumulate\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. This may affect the characteristics of the basic data in this study.\u003c/p\u003e \u003cp\u003e \u003cb\u003eDifferences in nutritional status, food composition, NLR and pre and post intervention SCFA levels in both groups\u003c/b\u003e \u003c/p\u003e \u003cp\u003eIn this study there was no difference in nutritional status before and after both in the Intervention group and the control group. Various mechanisms are involved in adverse nutritional changes in CKD patients. Poor dietary intake caused by uremia-induced anorexia alone does not explain adverse nutritional changes. There are additional contributing causes, such as persistent inflammation, acidosis, multiple hormonal disorders, comorbidities, and physical inactivity. Many studies on the nutritional status of CKD patients reveal that wastage and abnormalities of protein energy can be caused by inflammatory processes. Simple malnutrition refers to nutritional abnormalities caused by inadequate nutrient intake, while wasting caused by CKD refers to nutritional abnormalities that may be related to inflammation and cannot be corrected simply by improving diet. The International Society of Renal Nutrition and Metabolism (ISRNM) proposes a general nomenclature and diagnostic criteria for this malnutrition status in the context of CKD, Protein-energy wasting (PEW) is proposed to show concomitant loss in protein and energy storage in Chronic Kidney Disease patients.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn this study, there were differences in food composition in the Intervention group and the control group, especially the total fat of the food given. Among glyceride fractions, olive oil exhibits a high content of fatty acids and in particular high monounsaturated fatty acids (MUFAs). This olive oil compound has shown potential as an antioxidant, anti-inflammatory and antimicrobial agent. However, its concentration is related to various factors: olive variety, environmental factors, harvest and extraction time, as well as storage conditions this olive oil compound has shown potential as an antioxidant, anti-inflammatory and antimicrobial agent.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eOur study showed significant differences were found in NLR levels in routine blood samples before and after administration of EVOO in the intervention group and control group. A recent meta-analysis of randomized controlled trials evaluated the effects of regular olive oil intake on inflammation. The authors reported reduced levels of IL-6, tumor necrosis factor-α (TNF-α) and CRP, which are the three indicators of plasma inflammation considered. Such beneficial effects were demonstrated in studies when EVOO was taken regularly for more than 3 months. The participants' overall health status should also be considered, as the strongest positive effects were reported among the unhealthy group (type 2 diabetes mellitus or at risk of CVD). Another meta-analysis of 3,106 participants also showed a significant reduction in IL-6 and CRP levels, when olive oil was consumed as an additional or natural intake. Adherence to high-phenol Virgin Olive Oil breakfast decreased postprandial inflammatory response, reducing plasma lipopolysaccharide levels in patients with metabolic syndrome. The higher polyphenol content of EVOO may mediate beneficial effects as anti-inflammatory effects have been demonstrated in vitro. Anti-inflammatory effects of EVOO-enriched phenolic compounds have also been reported in adipose tissue in rats, with anti-atherosclerotic effects. The higher polyphenol content of EVOO may mediate beneficial effects as anti-inflammatory effects have been demonstrated in vitro. Anti-inflammatory effects of EVOO-enriched phenolic compounds have also been reported in adipose tissue in rats, with anti-atherosclerotic effects. The higher polyphenol content of EVOO may mediate beneficial effects as anti-inflammatory effects have been demonstrated in vitro. Anti-inflammatory effects of EVOO-enriched phenolic compounds have also been reported in adipose tissue in rats, with anti-atherosclerotic effects.\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eNeutrophil-Lymphocyte Ratio has been included as a blood-based inflammatory biomarker because it can reflect a balance between innate (neutrophil) and adaptive (lymphocyte) immune responses. NLR increases based on the degree of obesity and indicates a high circulating neutrophil count, and in individuals with obesity, this can be considered an acute inflammatory response to a chronic inflammatory state. More recently, low-quality diets have been shown to be associated with higher inflammatory status as measured by NLR in older Spanish populations. With respect to CRP, a systematic review and meta-analysis of randomized controlled trials showed a notable decrease in CRP (SMD: -0.11.95% CI: -0.21, -0.01, p\u0026thinsp;=\u0026thinsp;0.038) after oleic acid supplementation in adults and a minimum intervention duration of 4 weeks.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn this study, differences were found in the levels of SCFA in fecal samples before and after administration of EVOO in the Intervention group and control group where EVOO administration affected intestinal mucosal health and supported intestinal microbiota homeostasis by encouraging the production of intestinal immunoglobulin A (IgA), which was measured by enzyme-linked immunosorbent assay using fecal homogenate; dampens the production of inflammatory cytokines; supports the production and expression of cytokines and transcription factors involved in reducing inflammation and improving immune tolerance in the gut; and protects against intestinal oxidative injury through the potent antioxidant activity of EVOO phenolic extract.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e,\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eExtra Virgin Olive Oil affects the gut microbiota by reducing the abundance of pathogenic bacteria, stimulating the growth of beneficial bacteria, and increasing the production of microbe-produced short-chain fatty acids (SCFAs), which exert various anti-inflammatory effects, and can modulate the expression of various genes through epigenetic mechanisms.\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e This explains why there were significant levels of SCFA differences in similar stools in this study.\u003c/p\u003e \u003cp\u003eSeveral studies have shown that EVOO consumption increases \u003cem\u003eBacteroidetes\u003c/em\u003e and/or reduces the \u003cem\u003eFirmicutes/Bacteroidetes\u003c/em\u003e ratio, both of which are associated with athero protection. EVOO also increases the diversity of beneficial bacteria and certain gut bacteria that can be therapeutic for lipid immune disorders and obesity. In addition, some of the mechanisms involved in the relationship between EVOO and this disorder include antimicrobial activity, microbial cholesterol metabolism, and metabolites produced by bacteria. Specifically, EVOO modulates short-chain fatty acids produced by the gut microbiota, which can affect cholesterol metabolism and the immune system, and may play a role in weight gain by increasing satiety. \u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThe study had some limitations: the risk of over-reporting and memory bias in 24-hour food recall could not be ruled out.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eFrom this study it can be concluded that there are differences in inflammatory markers in the research group. After 2 weeks of EVOO administration, NLR was found to decrease in the Intervention group while NLR increased in the control group. SCFA levels increased in the Intervention group and did not increase in the control group, but EVOO affected Short SCFA levels in the gastrointestinal tract.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eIndonesian Ministry of Health. Basic Health Research Results (2018) Ministry of Health. RI 53, 1689\u0026ndash;1699 (2018)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAnothaisintawee T, Rattanasiri S, Ingsathit A, Attia J, Thakkinstian A (2009) Prevalence of chronic kidney disease: A systematic review and meta-analysis. Clin Nephrol 71:244\u0026ndash;254\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePernefri (2016) 9th report of the Indonesian Society of Nephrology. Perkumpulan Nefrol Indones 1\u0026ndash;46\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePahl MV, Vaziri, ND Immune Function in Chronic Kidney Disease (2015) Chronic Kidney Disease (Elsevier Inc. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/B978-0-12-411602-3.00024-X\u003c/span\u003e\u003cspan address=\"10.1016/B978-0-12-411602-3.00024-X\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCigarran S, Gonz\u0026aacute;lez E, Cases A (2017) Gut microbiota in chronic kidney disease ଝ. 7:9\u0026ndash;19\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbbas AK, Pillai, Shiv, Lichtman AH (2013) Basic immunology: functions and disorders of the immune system (4th). Basic immunology: functions and disorders of the immune system (4th)Elsevier Saunders\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJayne E, Marshall (2007) Le couvent des Dominicaines de Notre-Dame de Nazareth, un site monastique \u0026agrave; Aix-en-Provence. Analyse des donn\u0026eacute;es arch\u0026eacute;ologiques et premiers \u0026eacute;l\u0026eacute;ments de topographie p\u0026eacute;ri-urbaine m\u0026eacute;di\u0026eacute;vale. Sci (80-) 336:1268\u0026ndash;1273\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDai L et al (2017) Clinical global assessment of nutritional status as a predictor of mortality in chronic kidney disease patients. PLoS ONE 12:1\u0026ndash;17\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTonyali S, Ceylan C, Yahsi S, Karakan MS (2018) Does neutrophil and lymphocyte ratio indicate deterioration of kidney function? Ren Fail 40:209\u0026ndash;212\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGokce MI et al (2016) Re: Neutrophil-tolymphocyte ratio in clinical practice. J Can Urol Assoc 10:142\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYoshitomi R et al (2019) High neutrophil/lymphocyte ratio is associated with poor renal outcome in Japanese patients with chronic kidney disease. Ren Fail 41:238\u0026ndash;243\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRukavina Mikusic NL, Kouyoumdzian NM, Choi (2020) MR Gut microbiota and chronic kidney disease: evidence and mechanisms mediating novel communication in the gastrointestinal-renal axis. Pflugers arch. Eur J Physiol 472:303\u0026ndash;320\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang S et al (2019) Quantitative reduction of short-chain fatty acids, especially butyrate, contributes to the development of chronic kidney disease. Clin Sci 133:1857\u0026ndash;1870\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRysz J, Franczyk B, Cialkowska-Rysz A (2017) Gluba-Brz\u0026oacute;zka, A. Effect of diet on survival of patients with chronic kidney disease. Nutrition 9:1\u0026ndash;17\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNoce A et al (2021) Usefulness of minor polar compounds of extra virgin olive oil in the management of chronic kidney disease patients. Nutrition 13:1\u0026ndash;17\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJimenez-Lopez C et al (2020) Bioactive compounds and quality of extra virgin olive oil. Foods 9\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHyun YY et al (2017) Nutritional status in adults with predialysis chronic kidney disease: The KNOW-CKD study. J Korean Med Sci 32:257\u0026ndash;263\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCobo G, Lindholm B, Stenvinkel P (2018) Chronic inflammation in end-stage renal disease and dialysis. Nephrol Dial Transpl 33:iii35\u0026ndash;iii40\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarrone G et al (2022) Extra Virgin Olive Oil and Cardiovascular Protection in Chronic Kidney Disease. Nutrition 14:1\u0026ndash;19\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLuque-Sierra A, Alvarez-Amor L, Kleemann R, Mart\u0026iacute;n F, Varela LM (2018) Extra Virgin Olive Oil with Natural Phenolic Content Exerts Anti-Inflammatory Effects on Adipose Tissue and Reduces the Severity of Atherosclerosis Lesions in Ldlr-/- Mice.Leiden. Mol. Nutr. Food Res 62:1\u0026ndash;34\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoorthy M, Chaiyakunapruk N, Jacob SA, Palanisamy UD (2020) Prebiotic potential of polyphenols, their effects on gut microbiota and anthropometric/clinical markers: A systematic review of randomized controlled trials. Trends Food Sci Technol 99:634\u0026ndash;649\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGavahian M et al (2019) Health benefits of olive oil and its components: Impact on antioxidant activity of gut microbiota, and prevention of non-communicable diseases. Trends Food Sci Technol 88:220\u0026ndash;227\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDiseases C, Microbiota G, Santana LF, Pott A, Donadon J (2019) R. E ff ects of Olive Oil and Its Minor Components on. 4\u0026ndash;6\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIncani A et al (2016) Extra virgin olive oil phenolic extracts counteract the pro-oxidant effect of dietary oxidized lipids in human intestinal cells. Food Chem Toxicol 90:171\u0026ndash;180\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHern\u0026aacute;ez \u0026Aacute; et al (2014) Olive oil polyphenols enhance high-density lipoprotein function in humans: A randomized controlled trial. Arterioscler Thromb Vasc Biol 34:2115\u0026ndash;2119\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"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 Kidney Disease, Extra Virgin Olive Oil, NLR, SCFA","lastPublishedDoi":"10.21203/rs.3.rs-4576443/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4576443/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground and objective\u003c/h2\u003e \u003cp\u003e: People with Chronic Kidney Disease (CKD) generally has malnutrition and decrease immune system due to lower food intake and inflammation. To address the progression of CKD, the Neutrophil-to-Lymphocyte Ratio (NLR) has been identified as an independent risk factor. The decrease in short-chain fatty acids (SCFAs) in the feces and serum of CKD patients during disease progression suggests a link between gut microbiota and CKD. We proposed administering Extra Virgin Olive Oil (EVOO) to explore the impact of the intervention CKD patients and effects on inflammation and gut microbiota.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis study was randomized clinical trial design by the administration of EVOO. Thirty participants were taken from CKD patients undergoing hemodialysis (HD). The intervention group (15 participants) was administered with EVOO 40ml for 2 weeks, and 15 participants as a control group without EVOO. Body mass index was measured using anthropometric (body weigth dan heigth), NLR were taken from red blood cell and SCFA using prohealthy gut examination,\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003ethe study showed there were no differences between two group on nutritional status (both had normal status). Level of NRL significantly differents pre-and-post in intervention group, (5.07\u0026thinsp;\u0026plusmn;\u0026thinsp;7.35 vs 2.74\u0026thinsp;\u0026plusmn;\u0026thinsp;2.18 p\u0026thinsp;=\u0026thinsp;0.007), not for control group ( 3.86\u0026thinsp;\u0026plusmn;\u0026thinsp;2.21vs 4.26\u0026thinsp;\u0026plusmn;\u0026thinsp;2.56 p\u0026thinsp;=\u0026thinsp;0.196). There are not significant result for SCFA for intervention group (8.31\u0026thinsp;\u0026plusmn;\u0026thinsp;3.77 vs 8.92\u0026thinsp;\u0026plusmn;\u0026thinsp;3.88 p\u0026thinsp;=\u0026thinsp;0.670). and control group (11.50\u0026thinsp;\u0026plusmn;\u0026thinsp;4.80 vs 11.50\u0026thinsp;\u0026plusmn;\u0026thinsp;3.86 p\u0026thinsp;=\u0026thinsp;0.550). in addition, this study shown significant increased of energy intake, and carbohydrate on intervention group not in control group (p\u0026thinsp;\u0026lt;\u0026thinsp;0,005).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThis study reported the differences of NLR and SCFA levels and food intake in both groups, NLR as inflammatory markers significantly decreased in intervention group after 2 weeks of EVOO administration, while increased in control group. Moreover, EVOO affected Short SCFA levels in the gastrointestinal tract.\u003c/p\u003e","manuscriptTitle":"Virgin Olive Oil Extract as anti-inflammatory on Patients with Chronic Kidney Disease: Analysis of Neutrophil-to-lymphocyte Ratio and Short-Chain Fatty Acid","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-27 11:57:43","doi":"10.21203/rs.3.rs-4576443/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":"629b32ef-a9b6-4f24-bd88-7e10283e704b","owner":[],"postedDate":"June 27th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":33213347,"name":"Nutrition \u0026 Dietetics"}],"tags":[],"updatedAt":"2024-06-27T11:57:43+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-27 11:57:43","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4576443","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4576443","identity":"rs-4576443","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}