The intriguing role of Rifaximin in gut barrier chronic inflammation and in the treatment of Crohn’s disease

Abstract

The gastrointestinal tract acts as a functional unit organized as a semipermeable multilayer system, in which commensal gut microbiota represents the anatomical barrier. Recently, several studies have highlighted the involvement of gut microbiota in inflammatory bowel diseases (IBD) pathogenesis, in sustaining gut barrier chronic inflammation, and in conditioning disease course and therapeutical response. This evidence provides a rationale for treating patients with gut microbiota modifiers. Among these, Rifaximin represents a non-traditional antibiotic able to act as a 'eubiotic' on intestinal barrier. Area covered: The purpose of this narrative review is to explore the impact of Rifaximin on gut barrier and gut microbiota in IBD, in particular in Crohn's disease (CD), and to analyze its potential therapeutic applications. Expert opinion: The possibility of a beneficial activity of Rifaximin in chronic intestinal inflammation and CD has been debated and evaluated with different studies having obtained promising but still preliminary data. Larger trials are therefore needed. This gut-specific antibiotic could represent an alternative to systemic antibiotics thanks to its favorable safety profile and promising efficacy data. Rifaximin could exert, when appropriate, a synergic effect with immunomodulators in IBD, acting on both the microbial and the immunological sides of gut barrier impairment.

Rifaximin Alters Intestinal Microbiota and Prevents Progression of Ankylosing Spondylitis in Mice

“…In addition, some authors have reported that flora dysbiosis and TLR-4/NF-κB pathway activation were related to inflammasome initiation response (Porras et al, 2017). Studies have shown that rifaximin can suppress microbes-induced immune response through inhibiting the activation of NF-κB via the pregnane X receptor(Jin et al, 2017; Lopetuso et al, 2018). In our study, we focused on the TLR-4 which has been shown to play a key role in the many inflammatory diseases.…”

“…While the full effect of rifaximin on gut flora remains limited. Previous studies have shown that rifaximin can alter intestinal flora, inhibit bacterial attachment, prevent intestinal inflammation, and modulate gut barrier function (Xu et al, 2014; Lopetuso et al, 2018). This special feature distinguishes rifaximin from other systemic antibiotics.…”

Rifaximin as a Potential Treatment for IgA Nephropathy in a Humanized Mice Model

“…Here we investigated the effects of rifaximin, a broad-spectrum, non-absorbable, oral antibiotic, on α1KI-CD89Tg mice. Rifaximin inhibits microbe-induced immune response, acts on intestinal barrier integrity, and has a direct anti-inflammatory property through binding to the Pregnane X Receptor (PXR) and modulating gut microbiota [11,[25][26][27]. In particular, it is already demonstrated that rifaximin increases the relative abundance of beneficial intestinal bacteria, such as Lactobacillus and Bifidobacterium [28], reduces activation of T helper 17 cells [29], and attenuates TLR-4/NF-kB pathway activation in the gut [30].…”

“…It has been proven to be safe and well-tolerated. Previous studies have shown that rifaximin can alter intestinal flora, inhibit bacterial attachment, prevent intestinal inflammation, and modulate gut barrier function [11]. This special feature distinguishes rifaximin from other systemic antibiotics.…”

Effects of Rifaximin on Luminal and Wall-Adhered Gut Commensal Microbiota in Mice

“…Further clinical evidence led to the approval of the use of rifaximin for the treatment of diarrhea-predominant irritable bowel syndrome (IBS) [ 5 ]. Moreover, in the clinical practice, rifaximin is often prescribed for other gastrointestinal disorders, such as inflammatory bowel disease (IBD), small intestinal bacterial overgrowth (SIBO), and diverticular disease, because of its theoretical capability to modulate the intestinal microbiota [ 6 ].…”