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However, most previous studies of aging\u2010associated gut microbiota have relied on abundance\u2010based analyses, largely overlooking microbial networks and microbe\u2010host interactions. Here, we employed a co\u2010occurrence network approach to identify keystone taxa during aging in humans and mice. We found that centenarians harbor distinctive keystone taxa dominated by members of\n                    <jats:italic>Clostridium<\/jats:italic>\n                    , of which\n                    <jats:italic>Clostridium scindens<\/jats:italic>\n                    (\n                    <jats:italic>C. scindens<\/jats:italic>\n                    ) can significantly enhance microbial network stability, probably contributing to longevity and reduced susceptibility to age\u2010related diseases. Mechanistically,\n                    <jats:italic>C. scindens<\/jats:italic>\n                    produces indole\u20103\u2010acetic acid (IAA) from tryptophan via the enzymes amidase (AMIE) and aldehyde dehydrogenase (ALDH). Oral administration of either\n                    <jats:italic>C. scindens<\/jats:italic>\n                    or IAA effectively mitigates intestinal aging by restoring gut barrier dysfunction in aged mice. Further analysis revealed that\n                    <jats:italic>C. scindens<\/jats:italic>\n                    \u2010derived IAA restores intestinal dysfunction through activation of aryl hydrocarbon receptor (AHR) signaling, leading to upregulation of intestinal CLDN10, a key tight junction protein. Structurally, IAA enhances\n                    <jats:italic>Claudin<\/jats:italic>\n                    \u2010\n                    <jats:italic>10<\/jats:italic>\n                    transcription by promoting AHR binding to its promoter region. Our findings provide new insights into the characterization of microbial networks in centenarians and highlight that\n                    <jats:italic>C. scindens<\/jats:italic>\n                    and IAA may contribute to healthy longevity by promoting gut microecological stability and host homeostasis.\n                  <\/jats:p>","DOI":"10.1002\/imt2.70134","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T09:40:07Z","timestamp":1779183607000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Microbial keystone taxa and metabolic signatures in centenarians regulate intestinal homeostasis during aging"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6059-9244","authenticated-orcid":false,"given":"Wei\u2010Chuan","family":"Lin","sequence":"first","affiliation":[{"name":"State Key Laboratory of Magnetic Resonance and Imaging, National Centre for Magnetic Resonance in Wuhan, Innovation Academy of Precision Measurement Science and Technology Chinese Academy of Sciences (CAS) Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cui","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Magnetic Resonance and Imaging, National Centre for Magnetic Resonance in Wuhan, Innovation Academy of Precision Measurement Science and Technology Chinese Academy of Sciences (CAS) Wuhan China"},{"name":"University of Chinese Academy of Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He\u2010Hua","family":"Lei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Magnetic Resonance and Imaging, National Centre for Magnetic Resonance in Wuhan, Innovation Academy of Precision Measurement Science and Technology Chinese Academy of Sciences (CAS) Wuhan China"},{"name":"University of Chinese Academy of Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Magnetic Resonance and Imaging, National Centre for Magnetic Resonance in Wuhan, Innovation Academy of Precision Measurement Science and Technology Chinese Academy of Sciences (CAS) Wuhan China"},{"name":"University of Chinese Academy of Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Magnetic Resonance and Imaging, National Centre for Magnetic Resonance in Wuhan, Innovation Academy of Precision Measurement Science and Technology Chinese Academy of Sciences (CAS) Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Kai","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Magnetic Resonance and Imaging, National Centre for Magnetic Resonance in Wuhan, Innovation Academy of Precision Measurement Science and Technology Chinese Academy of Sciences (CAS) Wuhan China"},{"name":"University of Chinese Academy of Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin\u2010Zhi","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Faculty of Medicine, Laboratory for Drug Discovery from Natural Resource, State Key Laboratory of Quality Research in Chinese Medicine Macau University of Science and Technology Macao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing\u2010Wei","family":"Xiang","sequence":"additional","affiliation":[{"name":"Hubei Shizhen Laboratory, Department of Geriatrics &amp; Department of Orthopedic Surgery Hubei Provincial Hospital of Traditional Chinese Medicine (Affiliated Hospital of Hubei University of Chinese Medicine) Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Wen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hubei Shizhen Laboratory, Department of Geriatrics &amp; Department of Orthopedic Surgery Hubei Provincial Hospital of Traditional Chinese Medicine (Affiliated Hospital of Hubei University of Chinese Medicine) Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi\u2010Fu","family":"Pang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Longevity Science and Technology AIage Life Science Corporation Ltd. 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