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Akkermansia muciniphila Alleviates Olanzapine-Induced Hepatic Steatosis via the Gut Microbiota-IGFBP2/APOA1-Liver

Jing Wang1, Peiru Chen1, Yahui Deng1

  • 1Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Microbial Biotechnology
|December 11, 2025
PubMed

Insights

Akkermansia muciniphila may protect against olanzapine-induced fatty liver disease. This study shows A. muciniphila administration reduced liver injury in rats by altering gut microbiota and liver gene expression.

Area of Science:

  • Hepatology
  • Microbiome research
  • Metabolic dysfunction

Background:

  • Olanzapine, an atypical antipsychotic, is linked to a high risk of hepatic steatosis (fatty liver disease).
  • Individual susceptibility to olanzapine-induced liver damage varies.
  • Altered gut microbiota composition, particularly a decrease in Akkermansia muciniphila, is observed in patients with olanzapine-induced liver injury.

Purpose of the Study:

  • To investigate the therapeutic potential of Akkermansia muciniphila in mitigating olanzapine-induced hepatic steatosis.
  • To elucidate the mechanisms underlying the protective effects of A. muciniphila.

Main Methods:

  • Administered A. muciniphila to olanzapine-treated rats.
  • Analyzed gut microbiome composition and diversity.
  • Performed transcriptomic analysis of liver tissue.
  • Validated the role of IGFBP2 and APOA1 in cellular and animal models.

Main Results:

  • A. muciniphila administration significantly reduced hepatic lipid accumulation and liver injury in olanzapine-treated rats.
  • Microbiome analysis showed significant alterations post-A. muciniphila treatment.
  • Transcriptomic analysis identified IGFBP2 and APOA1 as key genes involved in A. muciniphila's protective effects.
  • Overexpression of IGFBP2 and APOA1 alleviated olanzapine-induced hepatic steatosis.

Conclusions:

  • Akkermansia muciniphila exerts hepatoprotective effects against olanzapine-induced fatty liver disease.
  • The protective mechanism involves the gut microbiota-IGFBP2/APOA1-liver axis.
  • A. muciniphila represents a potential microbiota-targeted therapeutic strategy for metabolic dysfunction associated with olanzapine treatment.
Keywords:
Akkermansia muciniphilaIGFBP2/APOA1gut microbiotagut‐liver axishepatic steatosisolanzapine

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