Colonic hypersensitivity is a major determinant of the efficacy of bloating treatment in constipation-predominant irritable bowel syndrome

Abstract

The pathophysiology of bloating is largely unknown, and many mechanisms have been proposed. An alteration of intestinal gas production may have a role in a subgroup of patients, but available data are conflicting. We have previously shown that hypersensitivity to colonic fermentation is associated with severe bloating in a subgroup of patients with low intestinal gas production. Accordingly, we evaluated whether modification of intestinal gas production improves bloating severity according to the presence of visceral hypersensitivity to colonic fermentation. Twenty-four IBS-C patients with severe bloating underwent intestinal gas production measurement by hydrogen breath test after lactulose, and a recto-sigmoid barostat test in order to evaluate sensitivity thresholds in a basal condition and after induction of colonic fermentation. The subjects were then randomly assigned to receive either rifaximin or placebo according to a double-blind, randomized, cross-over trial. Rifaximin induced an improvement of symptom severity. A post hoc analysis according to the presence of hypersensitivity to colonic fermentation shows that rifaximin induces a significant improvement in symptom severity only in normosensitive, hyperproducer patients. Modulation of colonic flora, in order to reduce fermentation, does not interfere with bloating severity in patients with visceral hypersensitivity, thus suggesting that in this subgroup of subjects gas production is not crucial for the onset of bloating.

Fecal Microbiota Alterations Associated With Diarrhea-Predominant Irritable Bowel Syndrome

“…Rifaximin (400 mg) were administered orally twice per day for 2 weeks to IBS-D patients ( Majewski and McCallum, 2007 ; Di Stefano et al, 2011 ). They were further followed up for an additional 10 weeks after treatment.…”

A Review of Microbiota and Irritable Bowel Syndrome: Future in Therapies

“…In one trial, rifaximin plus neomycin significantly improved severity of constipation and symptoms of bloating and straining for up to 4 weeks compared with neomycin plus placebo [ 111 ]. In the other trial, rifaximin significantly decreased bloating, abdominal pain, abdominal distension and flatulence compared with placebo [ 112 ]. Overall, data suggest that rifaximin is a relatively safe therapeutic option for patients with IBS-D.…”

New and emerging therapies for the treatment of irritable bowel syndrome: an update for gastroenterologists

“…The nonsystemic antibiotic rifaximin appears to have anti-inflammatory, host-response, and gut microbiota modulatory activities [Bajaj et al 2013; Brown et al 2010; Cheng et al 2010; Debbia et al 2008; DuPont and Jiang, 2004; Hopkins et al 2014; Jiang et al 2010a, 2010b; Maccaferri et al 2010; Mencarelli et al 2010, 2011; Schrodt et al 2013; Terc et al 2014; Xu et al 2014]. Rifaximin received regulatory approval for the treatment of IBS-D in May 2015; several studies indicated a favorable efficacy and safety profile for rifaximin in IBS-D (Table 3) [Di Stefano et al 2011; Pimentel et al 2006, 2011, 2014]. The identically designed, randomized, placebo-controlled, phase III TARGET 1 and 2 studies examined the safety and efficacy of rifaximin 550 mg 3 times daily for 2 weeks in patients with IBS-D [Pimentel et al 2011].…”