2. Academic Validation
  3. Akkermansia muciniphila Mediated the Preventive Effect of Disulfiram on Acute Liver Injury via PI3K/Akt Pathway

Akkermansia muciniphila Mediated the Preventive Effect of Disulfiram on Acute Liver Injury via PI3K/Akt Pathway

  • Microb Biotechnol. 2025 Jan;18(1):e70083. doi: 10.1111/1751-7915.70083.
Ruonan Zhang 1,  Xuewei Sun 2,  Han Lu 3,  Xinrui Zhang 4,  Mingyan Zhang 5,  Xuewen Ji 6,  Xinyi Yu 7,  Chengliang Tang 2,  Zihan Wu 2,  Yinghua Mao 2,  Jin Zhu 2,  Minjun Ji 1,  Zhan Yang 2
Affiliations

Affiliations

  • 1 Department of Pathogen Biology, Nanjing Medical University, Nanjing, China.
  • 2 Huadong Medical Institute of Biotechniques, Nanjing, China.
  • 3 The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  • 4 School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
  • 5 Jinling Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China.
  • 6 School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
  • 7 Department of Infectious Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
PMID: 39825784 DOI: 10.1111/1751-7915.70083
Abstract

Acetaminophen induced acute liver injury (ALI) has a high incidence and is a serious medical problem, but there is a lack of effective treatment. The enterohepatic axis is one of the targets of recent attention due to its important role in liver diseases. Disulfiram (DSF) is a multitarget drug that has been proven to play a role in a variety of liver diseases and can affect intestinal flora, but whether it can alleviate ALI is not clear. We utilised Bacterial 16S rRNA gene profiling, antimicrobial treatments, and faecal microbiota transplantation tests to explore whether DSF therapy for ALI is dependent on gut microbiota. Our findings indicate that DSF primarily restores intestinal microbiome balance by modulating the abundance of Akkermansia muciniphila (A. muciniphila), leading to significant alleviation of ALI symptoms in a gut microbiota dependent manner. We also found that A. muciniphila can promote the activation of PI3K/Akt pathway, correct the Bcl-2/Bax ratio, and further inhibit hepatocyte Apoptosis. In conclusion, DSF ameliorates ALI by modulating the intestinal microbiome and activating the PI3K/Akt pathway through A. muciniphila.

Keywords

Akkermansia muciniphila; PI3K/Akt pathway; acetaminophen; acute liver injury; disulfiram; gut microbiome.

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