AUTHOR=Jian Jie , Nie Mei-Tong , Xiang Baoyu , Qian Hui , Yin Chuan , Zhang Xin , Zhang Menghui , Zhu Xuan , Xie Wei-Fen 

TITLE=Rifaximin Ameliorates Non-alcoholic Steatohepatitis in Mice Through Regulating gut Microbiome-Related Bile Acids

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.841132

DOI=10.3389/fphar.2022.841132

ISSN=1663-9812

ABSTRACT=<p>Non-alcoholic steatohepatitis (NASH) is the progressive stage of non-alcoholic fatty liver disease (NAFLD). The non-absorbable antibiotic rifaximin has been used for treatment of irritable bowel syndrome, traveling diarrhea, and hepatic encephalopathy, but the efficacy of rifaximin in NASH patients remains controversial. This study investigated the effects and underlying mechanisms of rifaximin treatment in mice with methionine and choline deficient (MCD) diet-induced NASH. We found that rifaximin greatly ameliorated hepatic steatosis, lobular inflammation, and fibrogenesis in MCD-fed mice. Bacterial 16S rRNA sequencing revealed that the gut microbiome was significantly altered in MCD-fed mice. Rifaximin treatment enriched 13 amplicon sequence variants (ASVs) belonging to the groups <italic>Muribaculaceae</italic>, <italic>Parabacteroides</italic>, <italic>Coriobacteriaceae_UCG-002</italic>, <italic>uncultured Oscillospiraceae</italic>, <italic>Dubosiella</italic>, <italic>Rikenellaceae_RC9_gut_group</italic>, <italic>Mucispirillum</italic>, and <italic>uncultured Desulfovibrionaceae</italic>. However, rifaximin treatment also reduced seven ASVs in the groups <italic>Aerococcus</italic>, <italic>Oscillospiraceae</italic>, <italic>uncultured Ruminococcaceae</italic>, <italic>Bilophila</italic>, <italic>Muribaculaceae</italic>, <italic>Helicobacter</italic>, and <italic>Alistipes</italic> in MCD-fed mice. Bile acid-targeted metabolomic analysis indicated that the MCD diet resulted in accumulation of primary bile acids and deoxycholic acid (DCA) in the ileum. Rifaximin delivery reduced DCA levels in MCD-fed mice. Correlation analysis further showed that DCA levels were associated with differentially abundant ASVs modulated by rifaximin. In conclusion, rifaximin may ameliorate NASH by decreasing ileal DCA through alteration of the gut microbiome in MCD-fed mice. Rifaximin treatment may therefore be a promising approach for NASH therapy in humans.</p>