Rifaximin ameliorates hepatic encephalopathy and endotoxemia without affecting the gut microbiome diversity

Abstract

AIMTo determine the efficacy of rifaximin for hepatic encephalopathy (HE) with the linkage of gut microbiome in decompensated cirrhotic patients.METHODSTwenty patients (12 men and 8 women; median age, 66.8 years; range, 46-81 years) with decompensated cirrhosis (Child-pugh score > 7) underwent cognitive neuropsychological testing, endotoxin analysis, and fecal microbiome assessment at baseline and after 4 wk of treatment with rifaximin 400 mg thrice a day. HE was determined by serum ammonia level and number connection test (NCT)-A. Changes in whole blood endotoxin activity (EA) was analyzed by endotoxin activity assay. Fecal microbiome was assessed by 16S ribosome RNA (rRNA) gene sequencing.RESULTSTreatment with rifaximin for 4 wk improved hyperammonemia (from 90.6 ± 23.9 μg/dL to 73.1 ± 33.1 μg/dL; P < 0.05) and time required for NCT (from 68.2 ± 17.4 s to 54.9 ± 20.3 s; P < 0.05) in patients who had higher levels at baseline. Endotoxin activity was reduced (from 0.43 ± 0.03 to 0.32 ± 0.09; P < 0.05) in direct correlation with decrease in serum ammonia levels (r = 0.5886, P < 0.05). No statistically significant differences were observed in the diversity estimator (Shannon diversity index) and major components of the gut microbiome between the baseline and after treatment groups (3.948 ± 0.548 at baseline vs 3.980 ± 0.968 after treatment; P = 0.544), but the relative abundances of genus Veillonella and Streptococcus were lowered.CONCLUSIONRifaximin significantly improved cognition and reduced endotoxin activity without significantly affecting the composition of the gut microbiome in patients with decompensated cirrhosis.

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

“…Our study corroborates the findings of previous studies with no significant changes in overall gut microbiota composition in patients with MHE treated with rifaximin [9,26]. Furthermore, we were able to show that in parallel with the amelioration of symptoms, the gut microbiota composition remains stable also after the completion of rifaximin treatment.…”

“…In patients with liver cirrhosis, rifaximin modulates the bacterial composition of the gut microbiota without a consistent effect on microbiota composition detected in the faeces [9,26]. Studies on changes in the duodenal microbiota composition of these patients have not been published so far.…”

Rifaximin‐altered gut microbiota components associated with liver/neuropsychological functions in patients with hepatic encephalopathy: An exploratory data analysis of phase II/III clinical trials

“…The proportion of species of oral origin, such as Veillonella and Streptococcus , is reported to be high in the feces of cirrhotic patients . Rifaximin shows high antibacterial activity against Veillonella (minimal inhibitory concentration 50, 2 μg/mL) and Streptococcus (minimal inhibitory concentration 50, ≤0.03–0.12 μg/mL) and several studies have reported that RFX treatment decreases the relative abundances of the genera Veillonella and Streptococcus . Our findings on Streptococcus and Veillonella are in good agreement with these previous reports.…”

“…As RFX inhibits ammonia‐producing bacterial genera such as Clostridium and Streptococcus , it is thought to exert beneficial effects by modulating the bacterial composition of the gut microbiota . However, recent studies reported that treatment with RFX has only minor effects on intestinal bacterial composition in patients with decompensated liver cirrhosis and non‐alcoholic steatohepatitis . Thus, the effects of RFX on gut microbiota composition remain unclear.…”

Proton pump inhibitor therapy does not increase serum endotoxin activity in patients with cirrhosis

“…We assessed whole blood endotoxin activity (EA) using the commercially available Endotoxin Activity Assay (EAA) kit (Spectral Diagnostics, Toronto, Canada), as described elsewhere . In brief, the EAA is based on the principle that endotoxin binds to antiendotoxin antibodies and is delivered to neutrophils by complement receptors.…”