{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T22:14:21Z","timestamp":1789769661071,"version":"4.0.1"},"reference-count":34,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background: The reversal of liver fibrosis is crucial for improving outcomes in chronic liver disease. The gut\u2013liver axis, mediated by the intestinal microbiota, plays a significant role in this process. However, its dynamic changes and mechanisms during reversal remain unclear. This study aimed to systematically reveal these dynamics and explore the link between gut microbiota and metabolism in a spontaneous reversal model. Methods: Intestinal contents were collected from mouse model groups (fibrosis, 4-week reversal, and 12-week reversal). The use of 16S rRNA gene sequencing was employed to analyze gut microbiota structure, and untargeted metabolomics was used to profile metabolic changes. Differential metabolites and microbial taxa were identified using multivariate statistical analysis, followed by pathway enrichment analysis. Spearman correlation analysis was used to construct metabolite\u2013microbiota association networks across different reversal stages. Results: Metabolomic analysis showed significant alterations in multiple pathways during reversal. Linoleic and \u03b1-linolenic acid metabolism had a high impact in later stages. Taurine and biotin metabolism remained active throughout. Branched-chain amino acid degradation was enriched later. Microbiota analysis revealed significant structural shifts via beta-diversity. Bacteroidota decreased while Firmicutes increased in 4 weeks. Butyrate-producing families increased, and Akkermansia was enriched later. Integrated analysis demonstrated significant correlations between specific bacteria and metabolites, indicating a close microbiota\u2013metabolism association during reversal. Conclusions: This integrated multi-omics study delineates the potential dynamic reorganization of the gut microbiota and host metabolism during spontaneous liver fibrosis reversal. These findings provide a theoretical basis for understanding the gut\u2013liver axis mechanism in fibrosis reversal and for developing microbiota-targeted intervention strategies.<\/jats:p>","DOI":"10.3390\/metabo16060424","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T08:22:56Z","timestamp":1781684576000},"page":"424","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Gut\u2013Liver Axis Mechanisms Underlying Spontaneous Reversal of Liver Fibrosis: A Gut Microbiota-Metabolomics Analysis"],"prefix":"10.3390","volume":"16","author":[{"given":"Yuanying","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0879-4603","authenticated-orcid":false,"given":"Hao","family":"Chang","sequence":"additional","affiliation":[{"name":"Center of Liver Diseases, Peking University Ditan Teaching Hospital, Beijing 100015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxue","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingqing","family":"Yang","sequence":"additional","affiliation":[{"name":"Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Roehlen, N., Crouchet, E., and Baumert, T.F. 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