Gram-positive probiotics improves acetaminophen-induced hepatotoxicity by inhibiting leucine and Hippo-YAP pathway
Gut bacterial dysbiosis existed in DILI patients, with a decrease in Gram-positive bacteria and an increase in Gram-negative bacteria. A similar situation occurred in AILI mice. Pretreatment of BSL significantly improved APAP-induced disorders of gut bacteria and alleviated hepatic inflammation and necrosis. Transcriptome sequencing showed that BSL inhibited the hepatic damage pathways, such as Hippo and TGF-β signaling pathway. Metabolomic profiling revealed an obvious increase in oligopeptides containing branched-chain amino acids (BCAAs) in AILI mice, whereas these metabolites were significantly negatively correlated with the abundance of BSL, but positively with key genes of Hippo pathway. In vitro experiments showed that leucine exerted a dose-related exacerbation pattern on APAP-mediated hepatocellular injury. Mice supplemented with leucine resulted in the further overexpression of Yes-associated protein, an increase in oxidative stress, and a worsening of AILI.
Authors
- Weiyan Huang (ORCID: https://orcid.org/0009-0007-6298-1018)
- Yuanqing Zhu
- Bernd Schnabl (ORCID: https://orcid.org/0000-0002-6281-825X)
- Liuying Chen
- Quancheng Yang (ORCID: https://orcid.org/0000-0001-9963-7738)
- Peng Cao (ORCID: https://orcid.org/0000-0001-7739-6857)
- Huikuan Chu (ORCID: https://orcid.org/0000-0001-5349-8429)
- Wei Qian (ORCID: https://orcid.org/0000-0002-6232-0865)
- Li Xia Zhang (ORCID: https://orcid.org/0009-0004-1634-0832)
- Wenkang Gao (ORCID: https://orcid.org/0000-0003-3788-6426)
- Jingjin Che (ORCID: https://orcid.org/0000-0002-7305-6297)
- Ao Liu (ORCID: https://orcid.org/0009-0003-5810-5729)
- Gang Wang (ORCID: https://orcid.org/0000-0001-6500-5863)
- Hang Yuan
- Xin Liu (ORCID: https://orcid.org/0000-0002-6210-8100)
- Yue Chen
- Ling Yang (ORCID: https://orcid.org/0009-0006-3974-6100)
- Zhiyun Cheng (ORCID: https://orcid.org/0000-0002-9550-1056)
Institutions
- Union Hospital (HK)
- University of California San Diego (US)
- People's Liberation Army 401 Hospital (CN)
- Université Bourgogne Franche-Comté (FR)
- 181st Hospital of Chinese People's Liberation Army (CN)
- Union Hospital (CN)
- Huazhong University of Science and Technology (CN)
Publication Details
- Journal
- Cell & Bioscience
- Published
- 2025-03-07
- DOI
- https://doi.org/10.1186/s13578-025-01370-5
- Citations
- 3
- Primary Topic
- Drug-Induced Hepatotoxicity and Protection
- Type
- article
- Field-Weighted Citation Impact
- 4.67
Funders
- National Natural Science Foundation of China
- National Key Research and Development Program of China
- San Diego Digestive Diseases Research Center, School of Medicine, University of California, San Diego