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Frontiers in pharmacology
2022;13 841132.

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

Jie Jian, Mei-Tong Nie, Baoyu Xiang, Hui Qian, Chuan Yin, Xin Zhang, Menghui Zhang, Xuan Zhu, Wei-Fen Xie
Author Information
  1. Jie Jian: Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, China.
  2. Mei-Tong Nie: Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
  3. Baoyu Xiang: State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
  4. Hui Qian: Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, China.
  5. Chuan Yin: Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, China.
  6. Xin Zhang: Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, China.
  7. Menghui Zhang: State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
  8. Xuan Zhu: Department of Gastroenterology, First Affiliated Hospital of Nanchang University, Nanchang, China.
  9. Wei-Fen Xie: Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, China.
PMID: 35450049 DOI: 10.3389/fphar.2022.841132

Abstract

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 , , , , , , , and . However, rifaximin treatment also reduced seven ASVs in the groups , , , , , , and 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.

Keywords

bile acids deoxycholic acid farnesoid X receptor gut microbiome non-alcoholic steatohepatitis rifaximin

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