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Here we show that MASLD is characterized by coordinated disruption of bacterial, viral and fungal communities and by a disturbed phage-bacteria-metabolite axis associated with disease-related bile acid changes. Integrating shotgun metagenomics, fungal ITS2 sequencing, fecal metabolomics and clinical profiling in 210 patients with MASLD and 210 age- and gender-matched healthy controls, we find reduced microbial diversity and extensive remodeling of cross-kingdom ecological networks in MASLD.\n                    <jats:italic>Ruminococcus gnavus<\/jats:italic>\n                    emerges as an enriched central hub, while\n                    <jats:italic>Faecalibacterium prausnitzii<\/jats:italic>\n                    and its associated bacteriophages are depleted. Phage-host analyses further reveal reduced lytic activity against\n                    <jats:italic>R. gnavus<\/jats:italic>\n                    and loss of sulfur amino acid metabolism-related auxiliary metabolic genes, which may impair\n                    <jats:italic>F. prausnitzii<\/jats:italic>\n                    fitness. Diminished phage control may facilitate\n                    <jats:italic>R. gnavus<\/jats:italic>\n                    expansion, alongside increased fecal isodeoxycholic acid, a secondary bile acid implicated in hepatic steatosis. A diagnostic classifier integrating bacterial and viral features with clinical parameters distinguish MASLD from controls in our cohort and maintain predictive performance in two external datasets. Together, these findings uncover a disrupted phage-bacteria-metabolite axis in MASLD and provide a multi-kingdom framework\u00a0for non-invasive biomarker discovery and microbiome-targeted therapies.\n                  <\/jats:p>","DOI":"10.1038\/s41467-026-71981-0","type":"journal-article","created":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T06:54:19Z","timestamp":1776495259000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Multi-kingdom profiling reveals altered gut phage-bacteria-metabolite interactions in MASLD"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0680-0223","authenticated-orcid":false,"given":"Xiaofeng","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9603-4584","authenticated-orcid":false,"given":"Yanni","family":"Pu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanseul","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonghan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhao","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiadong","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanqin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5650-0165","authenticated-orcid":false,"given":"Mingfeng","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8890-4973","authenticated-orcid":false,"given":"Chengyan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6144-5618","authenticated-orcid":false,"given":"Shangyu","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5436-4219","authenticated-orcid":false,"given":"Long H.","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3976-6313","authenticated-orcid":false,"given":"Na","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1129-3147","authenticated-orcid":false,"given":"Yan","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4623-9012","authenticated-orcid":false,"given":"Taotao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,18]]},"reference":[{"key":"71981_CR1","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1002\/hep.31173","volume":"72","author":"JM Paik","year":"2020","unstructured":"Paik, J. 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