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Gut microbiome determines therapeutic effects of OCA on NAFLD by modulating bile acid metabolism

Jianjun Liu1,2, Jiayi Sun3, Jiangkun Yu4

  • 1State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming, Yunnan, 650091, China.

NPJ Biofilms and Microbiomes
|May 31, 2023
PubMed

Insights

Obeticholic acid (OCA) effectively treats non-alcoholic fatty liver disease (NAFLD) in mice by altering gut microbiota and modulating bile acids. This highlights the gut-liver axis

Area of Science:

  • Hepatology and Gastroenterology
  • Microbiome Research
  • Pharmacology

Background:

  • Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition lacking approved drug treatments.
  • Obeticholic acid (OCA), a bile acid derivative, shows promise in ameliorating NAFLD manifestations.
  • The gut-liver axis plays a crucial role in liver disease progression and treatment.

Purpose of the Study:

  • To investigate the role of gut microbiota in Obeticholic acid (OCA) treatment for non-alcoholic fatty liver disease (NAFLD) in a high-fat diet (HFD) mouse model.
  • To explore how OCA impacts gut microbiota composition and function in the context of NAFLD.
  • To elucidate the relationship between OCA-induced microbial changes and host bile acid metabolism.

Main Methods:

  • Induction of NAFLD in mice using a high-fat diet (HFD).
  • Administration of Obeticholic acid (OCA) to HFD-fed mice.
  • Antibiotic-induced microbiome depletion (AIMD) and fecal microbiota transplantation (FMT) to confirm microbiota's role.
  • Metagenomic and targeted metabolomics analyses to assess microbial and bile acid changes.

Main Results:

  • OCA treatment alleviated NAFLD histopathological lesions and restored liver function in HFD mice.
  • Gut microbiota critically mediates OCA's therapeutic effects, as confirmed by AIMD and FMT.
  • OCA intervention significantly increased the abundance of beneficial bacteria, including Akkermansia muciniphila and Bifidobacterium spp.
  • OCA modulated host bile acid profiles, decreasing hydrophobic acids and increasing conjugated forms, with strong correlations between microbial shifts and bile acid changes.

Conclusions:

  • Gut microbiota plays a pivotal role in Obeticholic acid (OCA) mediated amelioration of non-alcoholic fatty liver disease (NAFLD).
  • OCA intervention reshapes the gut microbial community, enriching specific bacteria that modulate host bile acid metabolism.
  • These microbial and metabolic alterations contribute to the therapeutic efficacy of OCA in NAFLD.

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