Mechanism of action and therapeutic benefit of rifaximin in patients with irritable bowel syndrome: a narrative review

Abstract

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder with a multifactorial pathophysiology. The gut microbiota differs between patients with IBS and healthy individuals. After a bout of acute gastroenteritis, postinfection IBS may result in up to approximately 10% of those affected. Small intestinal bacterial overgrowth (SIBO) is more common in patients with IBS than in healthy individuals, and eradication of SIBO with systemic antibiotics has decreased symptoms of IBS in some patients with IBS and SIBO. The nonsystemic (i.e. low oral bioavailability) antibiotic rifaximin is indicated in the United States and Canada for the treatment of adults with IBS with diarrhea (IBS-D). The efficacy and safety of 2-week single and repeat courses of rifaximin have been demonstrated in randomized, placebo-controlled studies of adults with IBS. Rifaximin is widely thought to exert its beneficial clinical effects in IBS-D through manipulation of the gut microbiota. However, current studies indicate that rifaximin induces only modest effects on the gut microbiota of patients with IBS-D, suggesting that the efficacy of rifaximin may involve other mechanisms. Indeed, preclinical data reveal a potential role for rifaximin in the modulation of inflammatory cytokines and intestinal permeability, but these two findings have not yet been examined in the context of clinical studies. The mechanism of action of rifaximin in IBS is likely multifactorial, and further study is needed.

Keywords: antibiotic; irritable bowel syndrome; mechanism; microbiota; pathophysiology; rifaximin.

Figure 1.

Study design and summary of findings from phase III studies of rifaximin (TARGET 1–3).^, DB, double-blind; OL, open-label; SC, stool collection; TARGET, Targeted, Nonsystemic Antibiotic Rifaximin Gut-Selective Evaluation of Treatment for IBS-D; TID, three times daily. ^*Primary efficacy end point defined as adequate relief of global IBS symptoms for ⩾2 of the first 4 weeks post-treatment. ^†Response defined as simultaneously achieving both a ⩾30% decrease from baseline in the mean weekly abdominal pain score and ⩾50% decrease from baseline in the number of days/week with Bristol Stool Scale type 6 or 7 stool for ⩾2 of the first 4 weeks posttreatment. The primary efficacy evaluation period occurred after the first double-blind repeat treatment phase. ^‡The second repeat treatment course was included in the study to evaluate the safety of repeat rifaximin treatment.

Figure 2.

Summary of gut microbiota alterations and antibiotic sensitivity in adults with IBS-D (TARGET 3).^– IBS-D, irritable bowel syndrome with diarrhea; TARGET, Targeted, Nonsystemic Antibiotic Rifaximin Gut-Selective Evaluation of Treatment for IBS-D; TID, 3 times daily.