{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:03:33Z","timestamp":1780617813550,"version":"3.54.1"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":58,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"the Open Project of the Key Laboratory of Viral Pathogenesis and Infection Prevention and Control (Jinan University), Ministry of Education","award":["2024VPPC-S02"],"award-info":[{"award-number":["2024VPPC-S02"]}]},{"name":"the Natural Science Foundation of Guangdong Province","award":["2025A1515012786"],"award-info":[{"award-number":["2025A1515012786"]}]},{"name":"the National Key &D Programs of China","award":["2022YFF0710702 and 2022YFF0710701"],"award-info":[{"award-number":["2022YFF0710702 and 2022YFF0710701"]}]},{"name":"the Guangzhou Joint Fund for Key Laboratory","award":["202201020381"],"award-info":[{"award-number":["202201020381"]}]},{"name":"the Medical Joint Fund of Jinan University","award":["YXJC2022004"],"award-info":[{"award-number":["YXJC2022004"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Biofilms Microbiomes"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic joint inflammation and systemic immune dysregulation. Emerging evidence suggests that the gut microbiome plays an important role in immune modulation in RA, yet the role of the gut virome remains poorly understood. Here, using the K\/BxN serum-transfer arthritis model, we systematically evaluated the potential role of fecal virome transplantation (FVT) in modulating gut ecology and innate inflammatory responses. Arthritic mice exhibited marked alterations in gut virome composition compared with healthy controls. Administration of purified virus-like particles (VLPs) from healthy donors correlated with reductions in paw swelling, histopathological inflammation, bone erosion, circulating proinflammatory cytokines, and myeloid cell infiltration in inflamed tissues. In parallel, 16S rRNA sequencing showed that FVT remodeled the gut bacterial community toward a composition more similar to that of healthy controls. Targeted serum metabolomics revealed increased levels of microbiota-derived tryptophan metabolites, including indole-3-lactic acid and related indole derivatives, suggesting a link between gut microbial remodeling and systemic immunometabolic regulation. Collectively, these findings indicate that FVT may attenuate inflammatory arthritis by remodeling gut microbial ecology, potentially involving virome\u2013bacteriome interactions and immunometabolic pathways.<\/jats:p>","DOI":"10.1038\/s41522-026-00980-2","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T17:55:13Z","timestamp":1775670913000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fecal virome transplantation attenuates arthritis in mice by remodeling gut ecology, systemic tryptophan metabolism, and innate immune responses"],"prefix":"10.1038","volume":"12","author":[{"given":"Lun","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Difen","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhua","family":"Ou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoming","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"key":"980_CR1","doi-asserted-by":"publisher","first-page":"2023","DOI":"10.1016\/S0140-6736(16)30173-8","volume":"388","author":"JS Smolen","year":"2016","unstructured":"Smolen, J. S., Aletaha, D. & McInnes, I. B. Rheumatoid arthritis. Lancet 388, 2023\u20132038 (2016).","journal-title":"Lancet"},{"key":"980_CR2","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1016\/S0140-6736(23)02650-8","volume":"403","author":"J Rech","year":"2024","unstructured":"Rech, J. et al. Abatacept inhibits inflammation and onset of rheumatoid arthritis in individuals at high risk (ARIAA): a randomised, international, multicentre, double-blind, placebo-controlled trial. Lancet 403, 850\u2013859 (2024).","journal-title":"Lancet"},{"key":"980_CR3","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.1001\/jama.2018.13103","volume":"320","author":"D Aletaha","year":"2018","unstructured":"Aletaha, D. & Smolen, J. S. Diagnosis and management of rheumatoid arthritis: a review. Jama 320, 1360\u20131372 (2018).","journal-title":"Jama"},{"key":"980_CR4","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1111\/imr.13359","volume":"325","author":"A Lamba","year":"2024","unstructured":"Lamba, A. & Taneja, V. Gut microbiota as a sensor of autoimmune response and treatment for rheumatoid arthritis. Immunol. Rev. 325, 90\u2013106 (2024).","journal-title":"Immunol. Rev."},{"key":"980_CR5","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1038\/s41584-021-00585-3","volume":"17","author":"MM Zaiss","year":"2021","unstructured":"Zaiss, M. M., Joyce Wu, H. J., Mauro, D., Schett, G. & Ciccia, F. The gut-joint axis in rheumatoid arthritis. Nat. Rev. Rheumatol. 17, 224\u2013237 (2021).","journal-title":"Nat. Rev. Rheumatol."},{"key":"980_CR6","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1038\/s41423-021-00661-4","volume":"18","author":"W Yang","year":"2021","unstructured":"Yang, W. & Cong, Y. Gut microbiota-derived metabolites in the regulation of host immune responses and immune-related inflammatory diseases. Cell Mol. Immunol. 18, 866\u2013877 (2021).","journal-title":"Cell Mol. Immunol."},{"key":"980_CR7","doi-asserted-by":"publisher","first-page":"103912","DOI":"10.1016\/j.autrev.2025.103912","volume":"24","author":"XY Qi","year":"2025","unstructured":"Qi, X. Y. et al. Gut microbiota in rheumatoid arthritis: mechanistic insights, clinical biomarkers, and translational perspectives. Autoimmun. Rev. 24, 103912 (2025).","journal-title":"Autoimmun. Rev."},{"key":"980_CR8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.104113","volume":"81","author":"Z Cao","year":"2022","unstructured":"Cao, Z. et al. The gut virome: a new microbiome component in health and disease. EBioMedicine 81, 104113 (2022).","journal-title":"EBioMedicine"},{"key":"980_CR9","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1016\/j.chom.2021.03.020","volume":"29","author":"MR Mangalea","year":"2021","unstructured":"Mangalea, M. R. et al. Individuals at risk for rheumatoid arthritis harbor differential intestinal bacteriophage communities with distinct metabolic potential. Cell Host Microbe 29, 726\u2013739.e725 (2021).","journal-title":"Cell Host Microbe"},{"key":"980_CR10","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1136\/annrheumdis-2021-221267","volume":"81","author":"Y Tomofuji","year":"2022","unstructured":"Tomofuji, Y. et al. Whole gut virome analysis of 476 Japanese revealed a link between phage and autoimmune disease. Ann. Rheum. Dis. 81, 278\u2013288 (2022).","journal-title":"Ann. Rheum. 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Transfer of modified gut viromes improves symptoms associated with metabolic syndrome in obese male mice. Nat. Commun. 15, 4704 (2024).","journal-title":"Nat. Commun."},{"key":"980_CR17","doi-asserted-by":"publisher","first-page":"2122","DOI":"10.1136\/gutjnl-2019-320005","volume":"69","author":"TS Rasmussen","year":"2020","unstructured":"Rasmussen, T. S. et al. Faecal virome transplantation decreases symptoms of type 2 diabetes and obesity in a murine model. Gut 69, 2122\u20132130 (2020).","journal-title":"Gut"},{"key":"980_CR18","doi-asserted-by":"crossref","unstructured":"Zhao, X. et al. Commensal viruses promote intestinal stem cell regeneration following radiation damage by inhibiting hyperactivation of RIG-I and notch signals. Adv. Sci. 12, e05204 (2025).","DOI":"10.1002\/advs.202505204"},{"key":"980_CR19","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-024-01820-1","volume":"12","author":"TS Rasmussen","year":"2024","unstructured":"Rasmussen, T. S. et al. 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Live Akkermansia muciniphila boosts dendritic cell retinoic acid synthesis to modulate IL-22 activity and mitigate colitis in mice. Microbiome 12, 275 (2024).","journal-title":"Microbiome"},{"key":"980_CR28","first-page":"730","volume":"21","author":"J Hu","year":"2023","unstructured":"Hu, J. et al. Tripterygium hypoglaucum extract ameliorates adjuvant-induced arthritis in mice through the gut microbiota. Chin. J. Nat. Med. 21, 730\u2013744 (2023).","journal-title":"Chin. J. Nat. Med."},{"key":"980_CR29","doi-asserted-by":"publisher","first-page":"1736","DOI":"10.1002\/art.42616","volume":"75","author":"Y Luo","year":"2023","unstructured":"Luo, Y. et al. Alteration of gut microbiota in individuals at high-risk for rheumatoid arthritis associated with disturbed metabolome and the initiation of arthritis through the triggering of mucosal immunity imbalance. Arthritis Rheumatol. 75, 1736\u20131748 (2023).","journal-title":"Arthritis Rheumatol."},{"key":"980_CR30","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.1038\/s12276-023-01028-7","volume":"55","author":"SK Seo","year":"2023","unstructured":"Seo, S. K. & Kwon, B. Immune regulation through tryptophan metabolism. Exp. Mol. Med. 55, 1371\u20131379 (2023).","journal-title":"Exp. Mol. Med."},{"key":"980_CR31","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05470-4","volume":"9","author":"HM Roager","year":"2018","unstructured":"Roager, H. M. & Licht, T. R. Microbial tryptophan catabolites in health and disease. Nat. Commun. 9, 3294 (2018).","journal-title":"Nat. Commun."},{"key":"980_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.micres.2025.128211","volume":"298","author":"T Pei","year":"2025","unstructured":"Pei, T. et al. The relationship between tryptophan metabolism and gut microbiota: Interaction mechanism and potential effects in infection treatment. Microbiol. Res. 298, 128211 (2025).","journal-title":"Microbiol. Res."},{"key":"980_CR33","doi-asserted-by":"publisher","DOI":"10.34133\/research.0728","volume":"8","author":"T Xiang","year":"2025","unstructured":"Xiang, T. et al. Aberrant tryptophan metabolism manipulates osteochondral homeostasis. Research 8, 0728 (2025).","journal-title":"Research"},{"key":"980_CR34","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41329-z","volume":"14","author":"K Wortelboer","year":"2023","unstructured":"Wortelboer, K. et al. Phage-microbe dynamics after sterile faecal filtrate transplantation in individuals with metabolic syndrome: a double-blind, randomised, placebo-controlled clinical trial assessing efficacy and safety. Nat. Commun. 14, 5600 (2023).","journal-title":"Nat. Commun."},{"key":"980_CR35","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2023.2236750","volume":"15","author":"JM Borin","year":"2023","unstructured":"Borin, J. M. et al. Fecal virome transplantation is sufficient to alter fecal microbiota and drive lean and obese body phenotypes in mice. Gut Microbes 15, 2236750 (2023).","journal-title":"Gut Microbes"},{"key":"980_CR36","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1038\/s41396-021-01107-5","volume":"16","author":"A Brunse","year":"2022","unstructured":"Brunse, A. et al. Fecal filtrate transplantation protects against necrotizing enterocolitis. ISME J. 16, 686\u2013694 (2022).","journal-title":"ISME J."}],"container-title":["npj Biofilms and Microbiomes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41522-026-00980-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41522-026-00980-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41522-026-00980-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T23:20:34Z","timestamp":1780615234000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41522-026-00980-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,8]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["980"],"URL":"https:\/\/doi.org\/10.1038\/s41522-026-00980-2","relation":{},"ISSN":["2055-5008"],"issn-type":[{"value":"2055-5008","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,8]]},"assertion":[{"value":"25 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"111"}}