Non-constipated Irritable Bowel Syndrome Research Articles

Metabolome-associated psychological comorbidities improvement in irritable bowel syndrome patients receiving a probiotic

Our recent randomized, placebo-controlled study in Irritable Bowel Syndrome (IBS) patients with diarrhea or alternating bowel habits showed that the probiotic Bifidobacterium longum (BL) NCC3001 improves depression scores and decreases brain emotional reactivity. However, the involved metabolic pathways remain unclear. This analysis aimed to investigate the biochemical pathways underlying the beneficial effects of BL NCC3001 using metabolomic profiling. Patients received probiotic (1x 1010CFU, n=16) or placebo (n=19) daily for 6 weeks. Anxiety and depression were measured using the Hospital Anxiety and Depression Scale. Brain activity in response to negative emotional stimuli was assessed by functional Magnetic Resonance Imaging. Probiotic fecal abundance was quantified by qPCR. Quantitative measurement of specific panels of plasma host-microbial metabolites was performed by mass spectrometry-based metabolomics. Probiotic abundance in feces was associated with improvements in anxiety and depression scores, and a decrease in amygdala activation. The probiotic treatment increased the levels of butyric acid, tryptophan, N-acetyl tryptophan, glycine-conjugated bile acids, and free fatty acids. Butyric acid concentration correlated with lower anxiety and depression scores, and decreased amygdala activation. Furthermore, butyric acid concentration correlated with the probiotic abundance in feces. In patients with non-constipation IBS, improvements in psychological comorbidities and brain emotional reactivity were associated with an increased abundance of BL NCC3001 in feces and specific plasma metabolites, mainly butyric acid. These findings suggest the importance of a probiotic to thrive in the gut and highlight butyric acid as a potential biochemical marker linking microbial metabolism with beneficial effects on the gut-brain axis.

Treatment of non-constipated irritable bowel syndrome with the histamine 1 receptor antagonist ebastine: a randomised, double-blind, placebo-controlled trial

ObjectiveWe evaluated the histamine 1 receptor antagonist ebastine as a potential treatment for patients with non-constipated irritable bowel syndrome (IBS) in a randomised, placebo-controlled phase 2 study.MethodsNon-constipated patients with IBS...

Collinsella aerofaciens as a predictive marker of response to probiotic treatment in non-constipated irritable bowel syndrome

ABSTRACT Probiotics are exploited for adjuvant treatment in IBS, but reliable guidance for selecting the appropriate probiotic to adopt for different forms of IBS is lacking. We aimed to identify markers for recognizing non-constipated (NC) IBS patients that may show significant clinical improvements upon treatment with the probiotic strain Lacticaseibacillus paracasei DG (LDG). To this purpose, we performed a post-hoc analysis of samples collected during a multicenter, double-blind, parallel-group, placebo-controlled trial in which NC-IBS patients were randomized to receive at least 24 billion CFU LDG or placebo capsules b.i.d. for 12 weeks. The primary clinical endpoint was the composite response based on improved abdominal pain and fecal type. The fecal microbiome and serum markers of intestinal (PV1 and zonulin), liver, and kidney functions were investigated. We found that responders (R) in the probiotic arm (25%) differed from non-responders (NR) based on the abundance of 18 bacterial taxa, including the families Coriobacteriaceae, Dorea spp. and Collinsella aerofaciens, which were overrepresented in R patients. These taxa also distinguished R (but not NR) patients from healthy controls. Probiotic intervention significantly reduced the abundance of these bacteria in R, but not in NR. Analogous results emerged for C. aerofaciens from the analysis of data from a previous trial on IBS with the same probiotic. Finally, C. aerofaciens was positively correlated with the plasmalemmal vesicle associated protein-1 (PV-1) and the markers of liver function. In conclusion, LDG is effective on NC-IBS patients with NC-IBS with a greater abundance of potential pathobionts. Among these, C. aerofaciens has emerged as a potential predictor of probiotic efficacy.

FODMAP meal challenge test: a novel investigation to predict response to low-FODMAP diet in non-constipating irritable bowel syndrome.

Though a low-FODMAP diet improves 50% irritable bowel syndrome (IBS) patients, regional dietary variations, vegetarianism, and long-term nutritional consequences challenge its implementation. We aimed developing a FODMAP meal challenge test (FMCT). We prospectively studied whether (i) high- than low-FODMAP foods produce more breath H2 among IBS patients than controls; (ii) post-meal symptoms relate to breath H2 ; and (iii) novel FMCT predicts response to a low-FODMAP diet? Forty Rome III IBS and 20 healthy controls underwent an eight-hour H2 breath test following a low- (rice, brinjal, corn, and banana [450Kcal]) and a high-FODMAP meal (wheat, kidney bean, pulse, and card [450Kcal]). Breath H2 (every 15min) and symptoms following low- and high-FODMAP meals were recorded. IBS-symptom severity scores were recorded every month for 3-months on low-FODMAP diet. Forty Rome III IBS (19 Rome IV positive) were comparable to 20 controls in age and gender. IBS patients (n=39 excluding one H2 non-producer) and controls produced more breath H2 after high- (greater in IBS) than low-FODMAP meal. Post-meal symptoms were commoner in IBS (4/40 [10%] and 27/40 [67.5%] with low- and high-FODMAP, respectively [P<0.00001]; none in healthy). IBS patients developing post-high-FODMAP meal symptoms produced greater H2 (18PPM [IQR 10.5-23] vs 6 [0-7.2]; P<0.001). A positive FMCT (breath H2 >10PPM above basal with symptoms following high-FODMAP food) had sensitivity, specificity, and diagnostic accuracy of 78.6%, 66.6%, and 75.6%, respectively, to predict low-FODMAP diet response. The novel FMCT predicts response to a low-FODMAP diet in IBS.

Fecal short-chain fatty acids in non-constipated irritable bowel syndrome: a potential clinically relevant stratification factor based on catabotyping analysis

ABSTRACT The gut microbiota is believed to be a critical factor in the pathogenesis of IBS, and its metabolic byproducts, such as short-chain fatty acids (SCFAs), are known to influence gut function and host health. Despite this, the precise role of SCFAs in IBS remains a topic of debate. In this study, we examined the bacterial community structure by 16S rRNA gene profiling and SCFA levels by UPLC-MS/MS in fecal samples from healthy controls (HC; n = 100) and non-constipated patients (IBS-D and IBS-M; NC-IBS; n = 240) enrolled in 19 hospitals in Italy. Our findings suggest a significant difference between the fecal microbiomes of NC-IBS patients and HC subjects, with HC exhibiting higher intra-sample biodiversity. Furthermore, we were able to classify non-constipated patients into two distinct subgroups based on their fecal SCFA levels (fecal catabotype “high” and “low”), each characterized by unique taxonomic bacterial signatures. Our results suggest that the fecal catabotype with higher SCFA levels may represent a distinct clinical phenotype of IBS that could have implications for its diagnosis and treatment. This study provides a new perspective on the intricate relationship between the gut microbiome and bowel symptoms in IBS, underscoring the importance of personalized strategies for its management.

Randomized controlled pilot study assessing fructose tolerance during fructose reintroduction in non-constipated irritable bowel syndrome patients successfully treated with a low FODMAP diet.

Limited data exist to guide FODMAP (fermentable oligo-, di-, monosaccharides, and polyols) reintroduction to assess tolerance following a low FODMAP diet (LFD). Fructose reintroduction is often stepwise up to 7.5 g fructose (e.g., three tsp of honey). We aimed to determine the fructose tolerance threshold in non-constipated, LFD-responsive patients with irritable bowel syndrome (IBS) and assess whether stool microbiome predicted LFD response or fructose tolerance. Thirty-nine non-constipated IBS patients (51% women, mean age 33.7 years) completed a 4-week LFD. LFD responders were defined as those who reported adequate relief of IBS symptoms following the LFD. Responders were randomized to one of the three solution groups (100% fructose, 56% fructose/44% glucose, or 100% glucose) and received four doses (2.5, 5, 10, 15 g) for 3 days each. Patients reached their tolerance dose if their mean daily IBS symptom severity (visual analog scale [VAS], 0-100 mm) was >20 mm higher than post-LFD VAS. Stool samples before and after LFD were analyzed using shotgun metagenomics. Seventy-nine percent of patients were LFD responders. Most responders tolerated the 15 g sugar dose. There was no significant difference in mean dose tolerated between solution groups (p = 0.56). Compared to baseline, microbiome composition (beta diversity) significantly shifted and six bacterial genes in fructose and mannose metabolism pathways decreased after LFD, irrespective of LFD response or the solution group. Non-constipated, LFD-responsive IBS patients should be reintroduced to fructose in higher doses than 15 g to assess tolerance. LFD is associated with significant changes in microbial composition and bacterial genes involved in FODMAP metabolism.

Efficacy and Acceptability of Dietary Therapies in Non-Constipated Irritable Bowel Syndrome: A Randomized Trial of Traditional Dietary Advice, the Low FODMAP Diet, and the Gluten-Free Diet

Various diets are proposed as first-line therapies for non-constipated irritable bowel syndrome (IBS) despite insufficient or low-quality evidence. We performed a randomized trial comparing traditional dietary advice (TDA) against the low FODMAP diet (LFD) and gluten-free diet (GFD). Patients with Rome IV-defined non-constipated IBS were randomized to TDA, LFD, or GFD (the latter allowing for minute gluten cross-contamination). The primary end point was clinical response after 4 weeks of dietary intervention, as defined by ≥50-point reduction in IBS symptom severity score (IBS-SSS). Secondary end points included (1) changes in individual IBS-SSS items within clinical responders, (2) acceptability and food-related quality of life with dietary therapy, (3) changes in nutritional intake, (4) alterations in stool dysbiosis index, and (5) baseline factors associated with clinical response. The primary end point of ≥50-point reduction in IBS-SSS was met by 42% (n= 14/33) undertaking TDA, 55% (n= 18/33) for LFD, and 58% (n= 19/33) for GFD (P= .43). Responders had similar improvements in IBS-SSS items regardless of their allocated diet. Individuals found TDA cheaper (P < .01), less time-consuming to shop (P < .01), and easier to follow when eating out (P= .03) than the GFD and LFD. TDA was also easier to incorporate into daily life than the LFD (P= .02). Overall reductions in micronutrient and macronutrient intake did not significantly differ across the diets. However, the LFD group had the greatest reduction in total FODMAP content (27.7 g/day before intervention to 7.6 g/day at week 4) compared with the GFD (27.4 g/day to 22.4 g/day) and TDA (24.9 g/day to 15.2 g/day) (P < .01). Alterations in stool dysbiosis index were similar across the diets, with 22%-29% showing reduced dysbiosis, 35%-39% no change, and 35%-40% increased dysbiosis (P= .99). Baseline clinical characteristics and stool dysbiosis index did not predict response to dietary therapy. TDA, LFD, and GFD are effective approaches in non-constipated IBS, but TDA is the most patient-friendly in terms of cost and convenience. We recommend TDA as the first-choice dietary therapy in non-constipated IBS, with LFD and GFD reserved according to specific patient preferences and specialist dietetic input. gov: NCT04072991.

Comparative effectiveness of 5-hydroxytryptamine 3 receptor antagonists in irritable bowel syndrome: a network meta-analysis of randomized controlled studies.

BackgroundThere is evidence demonstrating the beneficial effects of 5-hydroxytryptamine 3 receptor antagonists (5-HT3) for the treatment of non-constipated irritable bowel syndrome (NC-IBS). We aimed to determine the comparative effectiveness of 5-HT3 antagonists in NC-IBS, as evidenced by the results of a network meta-analysis (NWM) of published relevant randomized controlled trials (RCTs).MethodsWe searched the PubMed/Medline, EMBASE, and Cochrane Library databases for relevant RCTs through September 2020 and data from each selected RCT were extracted. A Bayesian NWM was then performed to investigate the efficacy of 5-HT3 antagonists and to explore the effectiveness rank order in treating NC-IBS patients.ResultsTwenty-one eligible RCTs were identified and entered into this NWM. They included a total of 10,421 NC-IBS patients, randomized to alosetron, cilansetron, ondansetron, ramosetron, placebo, and mebeverine. The cumulative ranking probability for each intervention at the end of treatment period, was evaluated by means of surfaces under cumulative ranking (SUCRA) values. These results showed that alosetron had the best performance for global symptom improvement (SUCRA 0.82), cilansetron showed the best performance (SUCRA 0.90) for abdominal pain/discomfort improvement, while ondansetron (SUCRA 0.98) was by far the best choice concerning bowel habits/consistency improvement. The control regimens (mebeverine and placebo) represented the least efficacious interventions.ConclusionsThis NWM showed that 5-HT3 receptor antagonists performed better in comparison to control drugs. Consequently, this class of drugs may play an important role in improving the debilitating symptoms in NC-IBS patients, in particular those with diarrhea.

The effect of fecal microbiota transplantation on IBS related quality of life and fatigue in moderate to severe non-constipated irritable bowel: Secondary endpoints of a double blind, randomized, placebo-controlled trial.

BackgroundSeverity in irritable bowel syndrome (IBS) is associated to impaired quality of life and fatigue. Fecal microbiota transplantation (FMT) induces significant relief in gastro-intestinal related complaints. The objective was to evaluate the effect of FMT on the secondary endpoints: IBS-related quality of life and fatigue in patients with non-constipated IBS.MethodIn this double-blind randomized placebo-controlled, parallel-group, single-center study, we enrolled patients with non-constipated IBS, defined by the ROME 3 criteria. We randomly assigned participants (2:1) in blocks of six to active or placebo FMT. Responder in fatigue and quality of life were defined as a decrease of 20 points in total Fatigue Impact Scale score, and improvement of 14 points in the IBS-quality of life questionnaire, respectively. In a modified-intention-to-treat population, we excluded participants who did not undergo treatment or who were diagnosed with any other disease by pinch biopsies during the treatment procedure.FindingsBetween Jan1, and Oct 30, 2015, we recruited 90 participants and randomly assigned them to active treatment (n = 60) or placebo (n = 30). Three participants did not undergo FMT and four were excluded after diagnosis of microscopic colitis, leaving 83 for final modified intention-to-treat analysis (55 in the active treatment group and 28 in the placebo group). Significant improvement in QoL (Odds ratio (OR) 3,801; confidence interval (CI) = 1,309–11,042 p = 0.011) and fatigue (OR = 4,398; CI = 1,175–16,468 and p = 0,020) was found at six months. Absence of other self reported functional disorders and presence of depression at baseline is suggested to predict a lasting effect of FMT in QoL and fatigue, respectively.InterpretationFMT induced significant relief in quality of life and fatigue. Results suggest a lasting effect of FMT in subgroups that should be further investigated in future studies. Funding Helse Nord, Norway and the Norwegian Centre of Rural Medicine, University of Tromsø, Norway.

Effect of eradicating hydrogen-forming small intestinal bacterial overgrowth with rifaximin on body weight change.

Hydrogen formed by small intestinal bacterial overgrowth in patients with non-constipated irritable bowel syndrome has an inverse relationship with obesity. However, the effect of eradicating small intestinal hydrogen-producing bacterial overgrowth on the body weight of these patients has not yet been reported. The aim of this study was to investigate body weight changes after eradicating small intestinal bacterial overgrowth with rifaximin treatment in patients with non-constipated irritable bowel syndrome.We reviewed the charts of patients with non-constipated irritable bowel syndrome who showed abdominal symptoms with documented lactulose hydrogen breath test results in order to diagnose small intestinal bacterial overgrowth. A total of 153 patients were enrolled in the study and divided into quartiles according to body mass index (BMI) and body weight.In the lowest body weight quartile, the BMI and body weight were significantly increased (0.4 kg/m2, P = .038; 0.6 kg, P = .010, respectively) in patients with negative lactulose hydrogen breath tests after rifaximin treatment. However, there was no significant change in body weight in the other quartiles. Despite treatment with rifaximin for 12 weeks, there was no change in BMI or body weight in any group of patients with consistently positive lactulose hydrogen breath tests.Eradication of hydrogen formed by small intestinal bacterial overgrowth does not cause clinically significant changes in body weight.

Effect of Rice, Wheat, and Mung Bean Ingestion on Intestinal Gas Production and Postprandial Gastrointestinal Symptoms in Non-Constipation Irritable Bowel Syndrome Patients.

The aim of this study is to evaluate the effect of rice, mung bean, and wheat noodle ingestion on intestinal gas production and postprandial gastrointestinal (GI) symptoms in non-constipation irritable bowel syndrome (IBS) patients. Methods: Twenty patients (13 F, 46 ± 11 y) underwent 8 h breath test studies and GI symptom evaluations after standard rice, wheat, or mung bean noodle meals at 8:00 a.m. in a randomized crossover study with a 1-week washout period. The same meal was ingested at 12:00 p.m. Results: The H2 and CH4 concentration in the breath samples were similar at baseline (rice:wheat:mung bean, H2 = 3.6 ± 0.5:4.1 ± 0.5:4.0 ± 0.7 ppm, CH4 = 1.3 ± 0.3:2.1 ± 0.4:1.9 ± 0.4 ppm, p > 0.05). Beginning at the fifth hour after breakfast, H2 and CH4 concentrations significantly increased after wheat compared to rice and mung bean (8 h AUC H2 = 4120 ± 2622:2267 ± 1780:2356 ± 1722, AUC CH4 = 1617 ± 1127:946 ± 664:943 ± 584 ppm-min, respectively) (p < 0.05). Bloating and satiety scores significantly increased after wheat compared to rice (p < 0.05), and increased but did not reach statistical significance compared to mung bean (p > 0.05). A higher bloating score after wheat compared to rice and mung bean was observed clearly after lunch but not after breakfast. Conclusion: Wheat ingestion produced more intestinal gas and more bloating and satiety scores compared to rice and mung bean, especially after lunch. This provides insight into the role of intestinal gas in the development of bloating symptoms in IBS.

Changes in Fecal Calprotectin After Rifaximin Treatment in Patients With Nonconstipated Irritable Bowel Syndrome

BackgroundFecal calprotectin, an indicator of colonic inflammation, is associated with nonconstipated irritable bowel syndrome. Rifaximin is an antibiotic used to treat nonconstipated irritable bowel syndrome. We performed a retrospective review of patient charts to investigate the changes in fecal calprotectin levels and intestinal symptoms following treatment with rifaximin in patients with nonconstipated irritable bowel syndrome with elevated fecal calprotectin. MethodsThis study included 198 patients presenting with gastrointestinal complaints consistent with Rome III criteria for irritable bowel syndrome. We treated them with rifaximin for 4-12 weeks, until fecal calprotectin levels were normalized, and divided these into 4-, 8-, and 12-week groups according to the treatment period. Fecal calprotectin levels and gastrointestinal symptoms were assessed following rifaximin therapy. ResultsA total of 162 subjects achieved normalized fecal calprotectin values. Of these, most patients who used rifaximin for 8 or 12 weeks showed a significant improvement in gastrointestinal symptoms by the fourth week of treatment, and gradually improved symptoms after 4 weeks. Fecal calprotectin levels were reduced with concomitant improvement of clinical symptoms. In addition, 36 patients who had elevated fecal calprotectin even after 12 weeks of rifaximin treatment showed a gradual reduction in gastrointestinal symptoms and fecal calprotectin during the course of treatment for 12 weeks. ConclusionsThese findings suggest that fecal calprotectin might be a useful biomarker for measuring the effect of rifaximin therapy in nonconstipated irritable bowel syndrome patients with elevated fecal calprotectin values.

Double-Blind Placebo-Controlled Study of Rifaximin and Lactulose Hydrogen Breath Test in Gulf War Veterans with Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) occurs in up to 33% of Gulf War (GW) Veterans. Alterations in gut microflora including small intestinal bacterial overgrowth (SIBO) during deployment may play a role in development of IBS. Rifaximin is a minimally absorbed antibiotic speculated to improve IBS symptoms, in part, by restoring normal gut microflora. The aim of this study was to compare rifaximin to placebo on IBS symptoms and quality of life (QOL) in GW Veterans with IBS without constipation. A double-blind, placebo-controlled study was performed. One hundred and twenty-two GW Veterans with IBS (Rome III) from our database and referral to gastroenterology and internal medicine clinics were screened. After a 2-week run-in period, 50 patients were randomized (1:1) to receive either rifaximin 550 gm or placebo twice daily for 2weeks in a double-blind study. Patients were advised not to change their diet or medications during the study. The symptoms assessed were: (1) stool frequency, (2) stool consistency (Bristol stool scale, 1-7, very hard to watery), (3) urgency (1 = yes/0 = no daily for 7days), (4) severity of abdominal pain (0-4, none to severe), (5) severity of bloating (1-4, none to severe), and (6) global improvement scale (1-7, substantially worse to substantially improved). These were recorded for 7 consecutive days and then averaged across the 7days, to generate a continuous variable. The symptom data were compared after 2weeks of treatment. QOL was assessed using IBS-QOL. The lactulose hydrogen breath test (LHBT) was performed at baseline and after 2weeks of treatment. Fifty Veterans were randomized to receive treatment; 3 withdrew and 3 were lost to follow-up. Data were analyzed from 44 patients (38 men, 6 women, median age 52, range 33-77years). Rifaximin was not associated with significant improvement in global symptoms, abdominal pain, bloating, stool urgency, frequency, or consistency (all P ≥ 0.25) or QOL (all P ≥ 0.26). Normalization of SIBO by LHBT was not different between rifaximin- and placebo-treated Veterans (7 vs. 22%, P = 0. 54). Rifaximin was not effective in improving IBS symptoms and QOL in GW Veterans with non-constipated IBS.

Small intestinal bacterial overgrowth as a cause for irritable bowel syndrome: guilty or not guilty?

Small intestinal bacterial overgrowth (SIBO) has been proposed as a cause of irritable bowel syndrome (IBS). However, this relationship has been subject to controversy. This review aims to provide a current perspective on the SIBO-IBS hypothesis. Case-control studies evaluating the prevalence of SIBO in IBS and healthy individuals have shown conflicting results. Moreover, the tests available in routine clinical practice to diagnose SIBO are not valid and lack both sensitivity and specificity. Hence, interpreting the effect of interventions based on these tests is fraught with uncertainty. Furthermore, the SIBO-IBS hypothesis has paved the way to assess antibiotic therapy in nonconstipated IBS, with rifaximin, a nonabsorbable antibiotic, showing modest but significant clinical benefit. However, individuals were not tested for SIBO and the mechanism of action of rifaximin in IBS remains to be elucidated. Preliminary data suggest that rifaximin decreases microbial richness and previous studies have noted antibacterial interventions in IBS to reduce colonic fermentation and improve symptoms. The advent of rapid culture-independent molecular techniques is a promising tool that will seek to clarify and advance our understanding of the gut microbial function. The SIBO-IBS hypothesis lacks convincing evidence but remains under scrutiny. The mechanism resulting in symptom improvement after rifaximin treatment in some IBS individuals requires exploration. Novel molecular techniques provide an exciting and challenging opportunity to explore the host-gut microbiota interaction.

Efficacy and safety of 5-hydroxytryptamine 3 receptor antagonists in irritable bowel syndrome: A systematic review and meta-analysis of randomized controlled trials.

AimWe assessed the efficacy and safety of 5-hydroxytryptamine (5-HT3) receptor antagonists in adults with non-constipated irritable bowel syndrome (IBS) or diarrhea-predominant IBS (IBS-D).MethodsWe searched PubMed, MEDLINE, EMBASE, and the Cochrane Controlled Trials Register for randomized controlled trials (RCTs) involving adults with non-constipated IBS or IBS-D that compared 5-HT3 receptor antagonists with placebo or other conventional treatment. Dichotomous symptom data were pooled to obtain the relative risk (RR) and 95% confidence intervals (CIs) for improving global IBS symptoms, abdominal pain and abnormal bowel habits, or stool consistency symptoms after therapy, and adverse events, including constipation. Meta- analysis was performed with Mantel Haenszel method using Revman 5.3 software.ResultsWe included 21 RCTs; 16 were high quality (Jadad score ≥ 4). The pooled RR of global IBS symptoms improved by 5-HT3 receptor antagonists versus placebo or mebeverine was 1.56 (95% CI: 1.43–1.71); alosetron, ramosetron, and cilansetron had similar treatment effects. The pooled RR of abdominal pain relieved by 5-HT3 receptor antagonists versus placebo was 1.33 (95% CI: 1.26–1.39). The pooled RR showed that 5-HT3 receptor antagonists improved abnormal bowel habits or stool consistency symptoms (RR = 1.63, 95% CI: 1.33, 1.99). The pooled RR of adverse events following 5-HT3 receptor antagonist treatment was 1.15 (95% CI: 1.08, 1.22). Subgroup analysis indicated that alosetron had a high rate of adverse effects (RR = 1.16, 95% CI: 1.08, 1.25); adverse events following ramosetron treatment were not statistically significantly different. 5-HT3 receptor antagonists were likelier to cause constipation: the pooled RR of constipation developing with 5-HT3 receptor antagonist versus placebo was 3.71 (95% CI: 2.98–4.61). However, constipation was likelier in patients with non-constipated IBS after taking 5-HT3 receptor antagonists than in patients with IBS-D only (non-constipated IBS and IBS-D: RR = 5.28 [95% CI: 3.93, 7.08] vs. IBS-D only 3.24 [2.54, 4.12]).ConclusionsRamosetron, cilansetron, ondansetron, and alosetron are effective for treating non-constipated IBS and IBS-D. Our systematic review found rare serious adverse events.

Obesity Is Inversely Related to Hydrogen-Producing Small Intestinal Bacterial Overgrowth in Non-Constipation Irritable Bowel Syndrome

There have been inconsistent findings on the association of obesity and non-constipation irritable bowel syndrome (IBS). Small intestinal bacterial overgrowth (SIBO) with hydrogen (H2) gas forming-microflora causes non-constipation IBS. But, the effect of H2 producing SIBO on obesity in non-constipation IBS patients has not been studied yet. The aim of this study was to investigate the association between obesity and SIBO in non-constipation IBS patients. We reviewed the charts of patients who showed IBS symptoms along with the documented results of their lactulose hydrogen breath test (LHBT) for SIBO. Multivariate models were used to assess the association between obesity and SIBO. Four-hundred fifty-eight patients were retrospectively included in the study. Of the 485 IBS patients, 158 (30.7%) subjects had positive results for LHBT. Subjects without SIBO showed significantly higher levels of body mass index (24.8 vs. 23.3; P < 0.001) and waist circumference (86.5 vs. 82.7; P < 0.001) as compared to subjects with SIBO. In multivariate analysis, the odds ratios of SIBO were 0.396 (P = 0.018) for obesity and 0.482 (P = 0.021) for abdominal obesity. This is the first human study to demonstrate that obesity is inversely related to SIBO with H2 gas production in non-constipation IBS patients.

Old drug, new tricks: rifaximin is effective in the treatment of non-constipation irritable bowel syndrome

Old drug, new tricks: rifaximin is effective in the treatment of non-constipation irritable bowel syndrome

Effects of Rifaximin on Transit, Permeability, Fecal Microbiome, and Organic Acid Excretion in Irritable Bowel Syndrome

Objectives:Rifaximin relieves irritable bowel syndrome (IBS) symptoms, bloating, abdominal pain, and loose or watery stools. Our objective was to investigate digestive functions in rifaximin-treated IBS patients.Methods:In a randomized, double-blind, placebo-controlled, parallel-group study, we compared the effects of rifaximin, 550 mg t.i.d., and placebo for 14 days in nonconstipated IBS and no evidence of small intestinal bacterial overgrowth (SIBO). All subjects completed baseline and on-treatment evaluation of colonic transit by scintigraphy, mucosal permeability by lactulose–mannitol excretion, and fecal microbiome, bile acids, and short chain fatty acids measured on random stool sample. Overall comparison of primary response measures between treatment groups was assessed using intention-to-treat analysis of covariance (ANCOVA, with baseline value as covariate).Results:There were no significant effects of treatment on bowel symptoms, small bowel or colonic permeability, or colonic transit at 24 h. Rifaximin was associated with acceleration of ascending colon emptying (14.9±2.6 h placebo; 6.9±0.9 h rifaximin; P=0.033) and overall colonic transit at 48 h (geometric center 4.0±0.3 h placebo; 4.7±0.2 h rifaximin; P=0.046); however, rifaximin did not significantly alter total fecal bile acids per g of stool or proportion of individual bile acids or acetate, propionate, or butyrate in stool. Microbiome studies showed strong associations within subjects, modest associations with time across subjects, and a small but significant association of microbial richness with treatment arm (rifaximin vs. treatment).Conclusions:In nonconstipated IBS without documented SIBO, rifaximin treatment is associated with acceleration of colonic transit and changes in microbial richness; the mechanism for reported symptomatic benefit requires further investigation.

Modulation of the gut microbiota composition by rifaximin in non-constipated irritable bowel syndrome patients: a molecular approach

Rifaximin, with its low systemic absorption, may represent a treatment of choice for irritable bowel syndrome (IBS), mainly due to its ability to act on IBS pathogenesis, through the influence on gut microbiota. The aim of the present study was to assess, by biomolecular tools, the rifaximin active modulation exerted on gut microbiota of non-constipated IBS patients. Fifteen non-constipated IBS subjects were treated with 550 mg rifaximin three times a day for 14 days. Stool samples were collected before starting the treatment, at the end of it, and after a 6-week washout period. Real-time polymerase chain reaction, denaturing gradient gel electrophoresis, and next-generation sequencing were applied to all the samples to verify and quantify possible microbial fluctuations. Rifaximin treatment did not affect the overall composition of the microbiota of the treated subjects, inducing fluctuations in few bacterial groups, balanced by the replacement of homologs or complementary bacterial groups. Rifaximin appeared to influence mainly potentially detrimental bacteria, such as Clostridium, but increasing the presence of some species, such as Faecalibacterium prausnitzii. A decrease in the Firmicutes/Bacteroidetes ratio after 14 days of treatment and bacterial profiles with higher biodiversity were observed during the follow-up compared to baseline. Rifaximin treatment, although effective on IBS symptom relief and normalization of lactulose breath test, did not induce dramatic shifts in the microbiota composition of the subjects, stimulating microbial reorganization in some populations toward a more diverse composition. It was not possible to speculate on differences of fecal microbiota modification between responders vs nonresponders and to correlate the quali-/quantitative modification of upper gastrointestinal microbiota and clinical response.

Colonic spirochetosis is associated with colonic eosinophilia and irritable bowel syndrome in a general population in Sweden.

Irritable bowel syndrome (IBS) is a functional disorder defined by symptoms in the absence of overt pathology. Colonic spirochetosis (CS), defined by histologic observation of spirochetal strains of Brachyspira in colonic biopsies, is uncommon and considered of doubtful significance. We aimed to determine the prevalence of CS in the general population, identify subtle colon pathologies, and evaluate a link with symptoms of IBS. Colonoscopy was performed in 745 subjects (aged 19-70 years, mean age 51 years, 43% male) with biopsies (ileum and 4 colonic sites) from a random population sample, Stockholm, Sweden, who completed a validated questionnaire of gastrointestinal symptoms; IBS was identified by Rome III criteria. CS was identified by histology and immunohistochemistry. In a general population, 17 individuals (2.28%; 95% confidence interval, 1.2%-3.5%) were diagnosed as having CS by histology; 6 (35%) had IBS. CS was always present in the sigmoid colon, but only 14 rectal biopsies. Eosinophils were increased in colon biopsies in CS cases versus controls, in the transverse (P = .02), sigmoid colon (P = .001), and rectum (P = .0005) with subepithelial eosinophil clusters (P = .053). Lymphoid follicles (at any site) were present in 13 CS (P = .0003). There was a 3-fold increased risk of IBS in CS (odds ratio, 3.59; 95% confidence interval, 1.27-10.11; P = .015). Polyps and diverticular disease were similar in CS cases and controls. The prevalence of CS in a general population is 2% and associated with nonconstipating IBS. Colonic eosinophilia with lymphoid follicles may signify the presence of CS.