Gut Microbiota and Metabolomics Correlation in a Mouse Model of Acute-on-Chronic Liver Failure

Abstract Acute-on-chronic liver failure (ACLF) is a high-mortality syndrome often causing multi-organ failure. Recent studies emphasize the gut-liver axis, showing gut microbiota impacts liver function via bile acid regulation, fatty acid production, and immune modulation. Metabolomics reveals metabolic changes and potential biomarkers. This study explores gut microbiota and metabolic correlations to enhance ACLF diagnosis, treatment, and prognosis. In this study, Established groups included ALF, liver fibrosis (LF), and normal control groups, from which stool, blood, and liver samples were collected. Using 16S rRNA high-throughput sequencing, we analyzed gut microbiota abundance, diversity, community composition, and flora changes, identifying specific microorganisms within the ACLF group. Non-targeted metabolite analysis was conducted using GC/MS and LC/MS to identify differential metabolites in the ACLF group and correlate them with differential microbes. The results revealed no significant change in gut microbial abundance and increased diversity in the ACLF group. Anaplasma phylum, ClostridiaᵥadinBB60group, Ali stipes, Marvinbryantia, Lachnoclostridium and Ruminalococcus were significantly enriched in the ACLF group. Among them, Anaplasma sp. differed significantly in all control groups and was highly enriched in the ACLF group. In addition, using Spearman's analysis, ClostridiaᵥadinBB60group was positively correlated with taurocholic acid, and was associated with glycerophosphorylcholine (PC) (16: 1 (9E) /0: 0), PC (16: 1 (9E) /0: 0), (±) 12-hydroxy eicosatetraenoic acid (HETE) and lysophosphatidylcholine (LysoPC) (16: 1 (9Z) /0: 0) were negatively correlated. S. parapsilosis was negatively correlated with taurocholic acid, PC (18: 1 (17Z) /18: 1 (17Z) ) and L-isoleucine, and positively correlated with PC (20: 1 (9Z) /0: 0) and (±) 12-HETE. In conclusion, we elucidated the increased diversity of the gut microbiota and potential pathogenic microorganisms in ACLF, along with their association with key metabolites. Our study provides crucial insights for a deeper understanding of ACLF pathogenesis and the identification of potential therapeutic targets.