Effect of rifaximin on gut microbiota composition in advanced liver disease and its complications

Abstract

Liver cirrhosis is a paradigm of intestinal dysbiosis. The qualitative and quantitative derangement of intestinal microbial community reported in cirrhotic patients seems to be strictly related with the impairment of liver function. A kind of gut microbial "fingerprint", characterized by the reduced ratio of "good" to "potentially pathogenic" bacteria has recently been outlined, and is associated with the increase in Model for End-Stage Liver Disease and Child Pugh scores. Moreover, in patients presenting with cirrhosis complications such as spontaneous bacterial peritonitis (SBP), hepatic encephalopathy (HE), and, portal hypertension intestinal microbiota modifications or the isolation of bacteria deriving from the gut are commonly reported. Rifaximin is a non-absorbable antibiotic used in the management of several gastrointestinal diseases. Beyond bactericidal/bacteriostatic, immune-modulating and anti-inflammatory activity, a little is known about its interaction with gut microbial environment. Rifaximin has been demonstrated to exert beneficial effects on cognitive function in patients with HE, and also to prevent the development of SBP, to reduce endotoxemia and to improve hemodynamics in cirrhotics. These results are linked to a shift in gut microbes functionality, triggering the production of favorable metabolites. The low incidence of drug-related adverse events due to the small amount of circulating drug makes rifaximin a relatively safe antibiotic for the modulation of gut microbiota in advanced liver disease.

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].…”

Rifaximin as a rare cause of rhabdomyolysis in cirrhosis

“…In patients with normal hepatic function, rifaximin has limited systemic absorption. However, in patients with hepatic impairment (especially patients with Child‐Pugh C or MELD >25), systemic absorption increases 5. The reasons behind this are multifactorial, including increased intestinal permeability due to alterations in the mucosal barrier, inflammation, and changes in the gut microbiota 6.…”

Fat and hepatocellular carcinoma

“…Interestingly, in a mouse model, drugs able to modify the microbiome (e.g., rifaximin) may prevent HCC development. Rifaximin may additionally improve portal hypertension, spontaneous bacterial infection (SBP) risk, liver fibrosis and hepatic encephalopathy [85] . Actually, metabolic alterations have been associated with dysbiosis: ob-ob mice (homozygous for the obese mutation) have an imbalance of the intestinal microbiota with a decrease of Bacteroides and an increase in Firmicutes.…”