Abstract
Alcohol-associated liver disease (ALD), characterized by gut barrier disruption and microbial dysbiosis, is associated with significant depletion of the genus Bifidobacterium in patients, as evidenced by our cohort of 127 subjects. Functional screening revealed B. pseudocatenulatum as a protective strain. In a murine ALD model established with a Lieber–DeCarli ethanol diet, oral administration of B. pseudocatenulatum for 8 weeks ameliorated hepatomegaly, steatosis, and serum transaminase levels. Probiotic intervention restored intestinal barrier function, as indicated by reduced lipopolysaccharide-binding proteins and upregulated tight junction protein expression. Microbiome analysis revealed a mitigation of dysbiosis, with a reduction in pathogenic Escherichia-Shigella and Parabacteroides and an enrichment of beneficial Bifidobacterium and Blautia, concomitant with shifts in lipid metabolism. Mechanistically, B. pseudocatenulatum-derived short-chain fatty acids downregulated the expression of hepatic lipogenic genes (Cd36, Fasn, Accα) and pro-inflammatory cytokines (Il-1β, Ccl2, Tnf-α). These results suggest that B. pseudocatenulatum is a promising probiotic candidate for ALD management.
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Data availability
The raw sequence data reported in this paper have been deposited in the Genome Sequence Archive in the National Genomics Data Center, China National Center for Bioinformation/Beijing Institute of Genomics, Chinese Academy of Sciences (GSA: CRA009220), and are publicly accessible at https://ngdc.cncb.ac.cn/gsa.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (82502783); the Zhejiang Provincial Natural Science Foundation of China (LQ22H030013;2022-KY1-001-039); the Fundamental Research Funds for the Central Universities (2025ZFJH03); the State Key Laboratory for Diagnosis and Treatment of Infectious Disease Independent Project (zz202320); the Young Innovative Talents Support Program of Zhejiang Medical and Health Science and Technology Project (2022499572, 2022RC243); and the Young Innovative Talents Support Program of Zhejiang Chinese Medicine Science Technology Project (2024025437, 2024ZR152).
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Y.L. conceptualized the study design and experimental framework. L.Y., H.X. and X.B. conducted the experimental investigations and coordinated the specimen acquisition. W.W. performed nucleic acid library preparation and high-throughput sequencing and established analytical pipelines. D.S. spearheaded the computational analyses and bioinformatics interpretation. L.L. synthesized the experimental findings and composed the initial draft of the manuscript. All the authors provided final approval for publication.
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Li, Y., Yang, L., Xu, H. et al. Restoration of ethanol-induced Bifidobacterium pseudocatenulatum depletion ameliorates alcohol-associated liver disease. npj Biofilms Microbiomes (2026). https://doi.org/10.1038/s41522-026-00913-z
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DOI: https://doi.org/10.1038/s41522-026-00913-z
