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

Abstract

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.

Dietary and pharmacological treatment of abdominal pain in IBS

“…A recent study appraised several potential mechanisms of action of rifaximin in the treatment of non-constipated patients with IBS, including permeability, expression of barrier proteins and faecal microbiome. There were no significant effects relative to placebo 55. In summary, the efficacy and the mechanism leading to relief with this non-absorbable antibiotic are unclear.…”

Beneficial effect of butyrate‐producing Lachnospiraceae on stress‐induced visceral hypersensitivity in rats

“…Furthermore, rats receiving early‐life antibiotic treatment also displayed visceral hypersensitivity in adulthood and altered microbiota profiles . Moreover, supplementation with probiotics/prebiotics or non‐absorbed antibiotics can reverse IBS symptoms . However, the bacteria that are critical for IBS pathogenesis have not been identified, and recent results have been inconsistent.…”

Modulation of the gut microbiota: a focus on treatments for irritable bowel syndrome

“…The mechanism of action of rifaximin in IBS is unclear, but studies in patients with non-IBS-C receiving a 2-week course of treatment with rifaximin experienced only modest, although detectable, changes in fecal microbial profiles [117,118]. Additional preclinical [119] studies and human IBS fecal sample analysis [118,120,121] studies of rifaximin have supported that any changes in the fecal microbial profile are modest and not sustained.…”