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.

The Effect of Bacterial Infections, Probiotics and Zonulin on Intestinal Barrier Integrity

“…According to some studies, Proteobacteria proliferation creates a state of dysbiosis and contributes to an increased risk of endogenous and exogenous infections [ 68 ]. Rifaximin, modulates the secretion of proinflammatory cytokines and, due to low oral bioavailability, has little effect on the composition of gut microbiota [ 69 ]. A meta-analysis of 26 randomized controlled trials of adults with small intestinal bacterial overgrowth (SIBO) signified a high rate of SIBO eradication with rifaximin [ 70 ].…”

“…A meta-analysis of 26 randomized controlled trials of adults with small intestinal bacterial overgrowth (SIBO) signified a high rate of SIBO eradication with rifaximin [ 70 ]. The accuracy mechanism of action of rifaximin in this case is likely multifactorial and more research is needed; but, in the USA and Canada, rifaximin is indicated in adults with IBS therapy [ 69 ]. The Enterobacteriaceae family, which is widely distributed in the intestines, also includes pathogenic strains of Escherichia coli or Klebsiella spp.…”

Effects of the antibiotic rifaximin on cortical functional connectivity are mediated through insular cortex

“…Reduced endotoxemia and altered microbiota-associated metabolic function, with a change in fatty acids production, have been reported following Rifaximin treatment 128 . Furthermore, it seems that the mechanism of action of Rifaximin, despite its role as a gastrointestinal-targeting antibiotic, might extend beyond the GM, modulating the production of inflammatory cytokines and intestinal permeability 133 . Finally, Rifaximin treatments have been seen to promote beneficial gut bacteria such as Bifidobacteria and Lactobacilli in patients with gastrointestinal and liver disorders 134 , 135 .…”

Macrocycle-Antibiotic Hybrids: A Path to Clinical Candidates

“…Rifaximin, a member of the rifamycin family and a nonsystemic antibiotic, has been approved for the treatments of travelers' diarrhea, hepatic encephalopathy, and irritable bowel syndrome without constipation (Lexicomp, 2021). Its clinical benefits were thought to be mediated through altered gastrointestinal (GI) microbiota or dysbiosis (Chey et al, 2020). Antibacterial evaluations of 15 against a representative panel of GI bacteria revealed similarities with rifaximin (Yuan et al, 2020).…”