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However, the relationship between age\u2010associated microbial changes and host intestinal physiology remains not fully elucidated. Here, we employed Bama miniature pigs, a model with close gastrointestinal similarity to humans, to investigate the impact of fecal microbiota transplantation (FMT) from young or elderly human donors on gut structure, barrier integrity, plasma metabolites, and intestinal mucosal transcriptomics. FMT resulted in distinct gut microbial profiles, with elderly\u2010donor FMT reducing ileal villus height and tight junction proteins (ZO\u20101, claudin\u20101, and occludin) across multiple intestinal segments. At the species level,\n                    <jats:italic>Phocea massiliensis<\/jats:italic>\n                    predominated in young\u2010donor pigs, while\n                    <jats:italic>Blautia obeum<\/jats:italic>\n                    was enriched in elderly\u2010donor pigs. Plasma metabolomic analysis revealed increased 3\u2010methyloxindole, prostaglandin E3, and 2\u2010hydroxybutanoic acid but reduced Tyr\u2010Phe and 2\u2010hydroxyoctadecanoic acid in the elderly group. Among\n                    <jats:italic>B. obeum<\/jats:italic>\n                    \u2010associated metabolites, Tyr\u2010Phe and 2\u2010hydroxyoctadecanoic acid exhibited a positive correlation with certain intestinal tight junction protein levels, whereas prostaglandin E3 showed an inverse correlation. Further validation performed in IPEC\u20101 cells demonstrated that Tyr\u2010Phe elevated transepithelial electrical resistance (TEER), while prostaglandin E3 lowered this parameter. Transcriptomic profiling identified seven hub genes (\n                    <jats:italic>MX2<\/jats:italic>\n                    ,\n                    <jats:italic>ISG15<\/jats:italic>\n                    ,\n                    <jats:italic>IFI6<\/jats:italic>\n                    ,\n                    <jats:italic>IFIT1<\/jats:italic>\n                    ,\n                    <jats:italic>OAS1<\/jats:italic>\n                    ,\n                    <jats:italic>DHX58<\/jats:italic>\n                    ,\n                    <jats:italic>ISG12(A)<\/jats:italic>\n                    ) that were consistently downregulated in the ileal mucosa of pigs receiving elderly\u2010donor microbiota. These findings link age\u2010associated microbiota alterations to coordinated changes in intestinal architecture, barrier integrity, and host metabolic and transcriptional profiles, providing insights into microbial and metabolic features associated with age\u2010related intestinal decline.\n                  <\/jats:p>","DOI":"10.1111\/acel.70725","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:23:41Z","timestamp":1790162621000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transplantation of Elderly Human Gut Microbiota Into Pigs Reprograms Intestinal Barrier Function, Plasma Metabolome, and Gut Mucosal Transcriptomic Landscape"],"prefix":"10.1111","volume":"25","author":[{"given":"Jiaxin","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding China Agricultural University  Beijing 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhian","family":"Zhai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aoyu","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Duan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8154-1540","authenticated-orcid":false,"given":"Zhengyuan","family":"Zhai","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanling","family":"Hao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yalin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health Peking University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajun","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health Peking University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9348-5761","authenticated-orcid":false,"given":"Zhenlong","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3483-0729","authenticated-orcid":false,"given":"Yun","family":"Ji","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2025.106966"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/21688370.2018.1539595"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010020\u201001477\u20100"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2011.244"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2019.100938"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1021924"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2022.07.015"},{"key":"e_1_2_12_9_1","doi-asserted-by":"crossref","unstructured":"Chen C. 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