Eubiotic properties of rifaximin: Disruption of the traditional concepts in gut microbiota modulation

Abstract

Antibiotics are usually prescribed to cure infections but they also have significant modulatory effects on the gut microbiota. Several alterations of the intestinal bacterial community have been reported during antibiotic treatment, including the reduction of beneficial bacteria as well as of microbial alpha-diversity. Although after the discontinuation of antibiotic therapies it has been observed a trend towards the restoration of the original condition, the new steady state is different from the previous one, as if antibiotics induced some kind of irreversible perturbation of the gut microbial community. The poorly absorbed antibiotic rifaximin seem to be different from the other antibiotics, because it exerts non-traditional effects additional to the bactericidal/bacteriostatic activity on the gut microbiota. Rifaximin is able to reduce bacterial virulence and translocation, has anti-inflammatory properties and has been demonstrated to positively modulate the gut microbial composition. Animal models, culture studies and metagenomic analyses have demonstrated an increase in Bifidobacterium, Faecalibacterium prausnitzii and Lactobacillus abundance after rifaximin treatment, probably consequent to the induction of bacterial resistance, with no major change in the overall gut microbiota composition. Antibiotics are therefore modulators of the symbiotic relationship between the host and the gut microbiota. Specific antibiotics, such as rifaximin, can also induce eubiotic changes in the intestinal ecosystem; this additional property may represent a therapeutic advantage in specific clinical settings.

Long-Term Effect of Rifaximin with and without Lactulose on the Active Bacterial Assemblages in the Proximal Small Bowel and Faeces in Patients with Minimal Hepatic Encephalopathy

“…In rats on rifaximin, the transient reductions in stool coliform counts recover after rifaximin interruption, while rifaximin appears to produce durable reductions in duodenal bacteria [21][22][23][24]. Further studies in animal models, culture studies and metagenomic analyses have demonstrated an increase in Bifidobacterium, Faecalibacterium prausnitzii and Lactobacillus abundance after rifaximin treatment, also with no significant changes in the overall gut microbiota composition [21].…”

“…Further studies in animal models, culture studies and metagenomic analyses have demonstrated an increase in Bifidobacterium, Faecalibacterium prausnitzii and Lactobacillus abundance after rifaximin treatment, also with no significant changes in the overall gut microbiota composition [21]. In patients with other gastrointestinal diseases (e.g., diverticular disease, irritable bowel syndrome), the body of knowledge on the mode of action of rifaximin is larger.…”

“…In a previous study, rifaximin has been shown to induce a general shift towards a relative abundance of health conferring gut microbiota and the claim of rifaximin as a eubiotic has been made [21].…”

“…It can down-regulate the inflammatory response triggered by gut microbes via an inhibition of the nuclear factor-κB pathway, a reduction of the expression of pro-inflammatory cytokines and an alteration of toll-like receptor distribution [21,33,34].…”

Profiling the effects of rifaximin on the healthy human colonic microbiota using a chemostat model

“…Both bacterial culture and 16S sequencing data showed Bifidobacterium as highly prevalent in all models, with rifaximin exposure causing a decline in models A and C, and an increase in model B. Susceptibility of Bifidobacterium populations to each rifaximin formulation could explain these differences, as Bifidobacterium genus has been shown to be highly resistant to rifaximin, with MICs increasing up to 25 mg l -1 during antibiotic exposure [35, 36]. As observed in patient studies, [13, 15, 35] our culture and sequencing data showed recovery of the microbial populations affected by rifaximin instillation, although differences in the relative abundance of some bacterial groups were observed.…”