Review Article

Potential Mechanisms of Action of Rifaximin in the Management of Irritable Bowel Syndrome With Diarrhoea

M. Pimentel


Aliment Pharmacol Ther. 2016;43(S1):37-49. 

In This Article

Abstract and Introduction


Background The role of gut microbiota in the pathophysiology of irritable bowel syndrome (IBS) is supported by various lines of evidence, including differences in mucosal and faecal microbiota between patients with IBS and healthy individuals, development of post-infectious IBS, and the efficacy of some probiotics and nonsystemic antibiotics (e.g. rifaximin).

Aim To review the literature regarding the role of rifaximin in IBS and its potential mecha-nism(s) of action.

Methods A literature search was conducted using the terms 'rifaximin', 'irritable bowel syndrome' and 'mechanism of action'.

Results Rifaximin was approved in 2015 for the treatment of IBS with diarrhoea. In contrast to other currently available IBS therapies that require daily administration to maintain efficacy, 2-week rifaximin treatment achieved symptom improvement that persisted ≥12 weeks post-treatment. The mechanisms of action of rifaximin, therefore, may extend beyond direct bactericidal effects. Data suggest that rifaximin may decrease host proinflammatory responses to bacterial products in patients with IBS. In some cases, small intestinal bacterial overgrowth (SIBO) may play a role in the clinical symptoms of IBS. Because of the high level of solubility of rifaximin in the small intestine, rifaximin may reset microbial diversity in this environment. Consistent with this hypothesis, rifaximin has antibiotic efficacy against isolates derived from patients with SIBO.

Conclusion Resetting microbial diversity via rifaximin use may lead to a decrease in bacterial fermentation and a reduction in the clinical symptoms of IBS.


Irritable bowel syndrome (IBS) is a relapsing gastrointestinal (GI) disorder characterised by abdominal pain and discomfort, bloating and changes in bowel habit.[1] IBS is one of the most common functional GI disorders, with a prevalence in the general population that ranges from 5% to 15%.[2] In a large survey of 8386 patients from community-based practices, the prevalence of IBS was 10.5%.[3] Symptoms of IBS adversely affect quality of life, including social and psychological aspects, and are associated with considerable costs to the health care system.[2–6] The syndrome is subclassified according to predominant bowel habit: diarrhoea predominant (IBS-D), constipation predominant (IBS-C), mixed subtype (IBS-M) or unclassified (IBS-U).[2] Among patients surveyed in community-based practices, symptom profiles were evenly split between those patients with predominant diarrhoea (25.4%) and constipation (24.1%), and overall, more females than males are affected by IBS.[3] Diagnosis is based on clinical findings because of the absence of abnormal radiological or endoscopic findings and lack of a reliable biomarker test.[2] Although the aetiology of IBS is unknown, changes in composition of gut microbiota have been proposed to underlie the symptoms of IBS in some cases.[7–9]

Support for a gut microbiota aetiology includes the relative clinical success of dietary approaches and pharmacological agents that modulate gut flora, including use of some probiotics[2] and antibiotics, such as rifaximin.[2,10–16] Rifaximin exhibits a number of properties that may be beneficial for the management of patients with IBS-D. Indeed, rifaximin is a nonsystemic derivative of rifamycin that contains an extra pyrido-imidazole ring to minimise systemic absorption.[17] Rifaximin is highly soluble in the presence of bile acids, (e.g. levels found in the small intestine).[18] Data from experimental and clinical pharmacology studies indicate that rifaximin has broad antibiotic effects against GI aerobic and anaerobic Gram-positive and Gram-negative bacteria.[19,20] Antibiotic effects (e.g. time-kill effects) for many bacterial species were observed at GI drug concentrations considerably lower than those concentrations measured in stool samples following administration of conventional rifaximin doses.[21,22] Rifaximin is considered to impose a relatively low risk of bacterial resistance, when used as directed,[23–25] and the low systemic absorption may account for the favourable safety and tolerability profile comparable with placebo.[10,11,13,16,26] In the context of low systemic absorption, rifaximin may provide a more favourable safety profile than reported for oral systemic antibiotics, which have been associated with rare events of nephrotoxicity, ototoxicity and peripheral neuropathy with repeated administration.[20,27]

While the limited data have suggested rifaximin may have clinical utility in IBS-C, specifically, improving symptoms in combination with other drugs like neomycin – possibly through its effect on methane-producing bacteria[28] – rifaximin is only indicated for IBS with diarrhoea. Thus, this narrative review will focus on the utility of rifaximin in IBS-D. Articles included in the review were identified by a systematic search of PubMed, through October 28, 2014, using 'rifaximin' AND 'irritable bowel syndrome' AND 'mechanism of action' keywords for articles in English. Recent review articles were consulted for general information on disease burden, diagnosis, and treatment of IBS. Current original data publications of rifaximin use in IBS were also included. Bibliographies from included articles were reviewed manually for additional relevant studies. For the purposes of this review, the primary focus was the role of gut microbiota as an aetiological factor in symptoms of IBS as opposed to the potential role of other aetiologies (e.g. dysregulation of brain–gut axis, visceral hyperalgesia), which were considered beyond the scope of this review.