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

Abstract

Background: Gut microbiota play an essential role in the pathogenesis of hepatic encephalopathy (HE). Treatment strategies are directed to modulate intestinal microbiota profiles and their function by the administration of the non-absorbable disaccharide lactulose and the non-absorbable antibiotic rifaximin, which are required for long terms, but little is known on their long-term effect on gut microbiota composition and function. Aim: To characterize the active bacterial assemblages in duodenum and faeces in patients with minimal HE (MHE) before, during and after long-term therapy with rifaximin. Methods: We analysed the microbiota composition in 5 patients with liver cirrhosis and MHE treated either with rifaximin 550 mg bid alone continuously for a period of 3 months or combined with lactulose 30–60 mL daily for 3 months. In addition to clinical assessments of HE, biopsies from duodenum and stool samples were analysed for their specific bacterial community applying NGS after RNA isolation before treatment, after 3 months of treatment and 3 months after the end of treatment. Results: All 5 patients had a significant improvement of their MHE. Bacterial communities were different and distinct in duodenal samples and faeces. No statistically significant changes were found in the bacterial community profile at the different time points. Conclusion: Rifaximin therapy with and without lactulose over a period of 3 months does not affect the bacterial community composition. The improvement of HE with rifaximin is lasting also after the end of treatment and therefore a prolonged effect on microbiota metabolic function is suggested.

Disease severity and proton pump inhibitor use impact strongest on faecal microbiome composition in liver cirrhosis

“…We were interested in the effect of lactulose on the cirrhotic microbiome, since available data are conflicting, showing no major alterations of the faecal microbiome between lactulose user and non-user, but withdrawal of lactulose leads to the loss of beneficial species. 16,50,51 In our cohort only 11% of the cirrhotic patients used lactulose. On univariate analysis we found that lactulose had a weak, but significant, effect on microbiome composition, which did not remain significant in multivariate analysis.…”

“…However, in our cohort, other drugs influenced microbiome composition to a lesser extent. We were interested in the effect of lactulose on the cirrhotic microbiome, since available data are conflicting, showing no major alterations of the faecal microbiome between lactulose user and non‐user, but withdrawal of lactulose leads to the loss of beneficial species . In our cohort only 11% of the cirrhotic patients used lactulose.…”

Microbiome therapeutics for hepatic encephalopathy

“…87,88 However, several small studies in patients with minimal HE suggest that rifaximin exerts little influence on microbial community composition. 85,[89][90][91] Since these studies used 16S rRNA amplicon sequencing methods, the effect of rifaximin on changes to subtaxa like species or strains may have been missed. Some effects from microbiome therapies are species and even strain specific.…”

Liver Cirrhosis and Sarcopenia from the Viewpoint of Dysbiosis

“…However, the preventive effects of rifaximin on sarcopenia incidence or progression in LC patients remain unclear. Table 2 demonstrates randomized controlled trials (RCTs) published since 2010 regarding the effects of rifaximin on outcomes in patients with decompensated LC [ 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 ]. RCTs with the improvement of sarcopenia as a primary endpoint are not found.…”