Hyodeoxycholic acid alleviates non-alcoholic fatty liver disease through modulating the gut-liver axis

Junliang Kuang, Jieyi Wang, Yitao Li, Mengci Li, Mingliang Zhao, Kun Ge, Dan Zheng, Kenneth Chat Pan Cheung, Boya Liao, Shouli Wang, Tianlu Chen, Yinan Zhang, Congrong Wang, Guang Ji, Peng Chen, Hongwei Zhou, Cen Xie, Aihua Zhao, Weiping Jia*, Xiaojiao Zheng*Wei Jia*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

4 Citations (Scopus)


Non-alcoholic fatty liver disease (NAFLD) is regarded as a pandemic that affects about a quarter of the global population. Recently, host-gut microbiota metabolic interactions have emerged as distinct mechanistic pathways implicated in the development of NAFLD. Here, we report that a group of gut microbiota-modified bile acids (BAs), hyodeoxycholic acid (HDCA) species, are negatively correlated with the presence and severity of NAFLD. HDCA treatment has been shown to alleviate NAFLD in multiple mouse models by inhibiting intestinal farnesoid X receptor (FXR) and upregulating hepatic CYP7B1. Additionally, HDCA significantly increased abundances of probiotic species such as Parabacteroides distasonis, which enhances lipid catabolism through fatty acid-hepatic peroxisome proliferator-activated receptor alpha (PPARα) signaling, which in turn upregulates hepatic FXR. These findings suggest that HDCA has therapeutic potential for treating NAFLD, with a unique mechanism of simultaneously activating hepatic CYP7B1 and PPARα.
Original languageEnglish
Pages (from-to)1752-1766.e8
Number of pages24
JournalCell Metabolism
Issue number10
Early online date16 Aug 2023
Publication statusPublished - 3 Oct 2023

Scopus Subject Areas

  • Molecular Biology
  • Physiology
  • Cell Biology

User-Defined Keywords

  • bile acid
  • CYP7B1
  • farnesoid X receptor
  • hyodeoxycholic acid
  • Parabacteroides distasonis
  • PPARα


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