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The gut microbiome is a promising therapeutic target, yet mechanisms linking commensal gut bacteria to frailty and functional independence remain unclear. Using data from the Integrative Longevity Omics (ILO) cohort with 418 shotgun metagenomics samples, gut microbial diversity and species were analyzed against ADLs, IADLs, and Fried frailty phenotypes. Species-level alpha diversity declined with higher fatigability, while beta diversity related to ADLs, IADLs, and fatigability. Species such as Anareostipes hadrus associated with better functioning and less weight loss, whereas Clostridium innocuum linked to worse ADLs/IADLs and greater fatigability, informing candidates for mechanistic follow-up.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/gut-microbial-signatures-of-frailty-and-functional-independence-in-centenarians-and-older-adults/426306/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/gut-microbial-signatures-of-frailty-and-functional-independence-in-centenarians-and-older-adults/426306.png","ImageObject",300,407,{"name":92,"@type":93},"Mabel","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-22","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What dataset and study design were used to analyze gut microbiome signatures?","Question",{"text":112,"@type":113},"The study used data from the Integrative Longevity Omics (ILO) ongoing cohort, including 418 shotgun metagenomics samples from centenarians and their offspring.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were gut microbiome features related to frailty and functional measures?",{"text":117,"@type":113},"Associations were tested between microbial alpha/beta diversity and species with function measures (ADLs and IADLs) and Fried frailty phenotype domains, including physical activity, fatigability, grip strength, and weight loss.",{"name":119,"@type":110,"acceptedAnswer":120},"Which microbial species were identified as linked to better versus worse outcomes?",{"text":121,"@type":113},"Anareostipes hadrus was associated with improved ADLs and IADLs, lower fatigability, and reduced likelihood of substantial weight loss. Clostridium innocuum was associated with worse ADLs/IADLs and greater fatigability.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},426306,1791325947,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":14,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":24},7971474920318,"https://ap-avatar.wpscdn.com/avatar/74000ee537e6b0ca360?x-image-process=image/resize,m_fixed,w_180,h_180&k=1788430171632181674","Innovation in Aging, 2025, Vol. 9, No. S2 1325  \nAbstract citation ID: igaf122.4410  \nGUT MICROBIAL SIGNATURES OF FRAILTY AND FUNCTIONAL INDEPENDENCE IN CENTENARIANSAND OLDER ADULTS  \nMeghan Short1, Tanya Karagiannis2, Ye Chen2, Daniel Segrè3, Sarah Bald3, Stacy Andersen3, Thomas Perls3, and  \nPaola Sebastiani2, 1. Tufts University School of Medicine, Medford, Massachusetts, United States, 2. Tufts Medical Center, Boston, Massachusetts, United States, 3. Boston University, Boston, Massachusetts, United States  \nFrailty and functional limitations decrease quality of life for older adults and are associated with myriad health risks. The gut microbiome is a potential therapeutic avenue for promoting functioning among older adults, but a clearer understanding of mechanisms by which commensal gut bacteria may affect frailty and functional independence is needed. In this study, we analyzed data from an ongoing cohort study, Integrative Longevity Omics (ILO), which has 418 shotgun metagenomics samples of the gut microbiome from centenarians and their offspring. We measured associations of microbial alpha/beta diversity and species with function measures (activities of daily living [ADLs] and instrumental activities of daily living [IADLs]) and Fried frailty phenotype domains (physical activity, fatigability, grip strength, weight loss) . Species-level alpha diversity decreased with increasing Pittsburgh fatigability score(β=-0.0051, 95% CI:- 0.0098 to-0.0003, p = 0.038), adjusting for age, sex, and education. Beta diversity (Bray-Curtis dissimilarity) was associated with ADLs(R2=0.005, p = 0.002), IADLs(R2=0.005, p= 0.006), and fatigability(R2=0.010, p ≤0.001), adjusting for age, sex, and  \n1326 Innovation in Aging, 2025, Vol. 9, No. S2  \neducation using PERMANOVA. Finally, we identified several species associated with multiple frailty and functioning scores, including Anareostipes hadrus, which was associated with improved ADLs, IADLs, fatigability, and lower likelihood of substantial weight loss, and is a known anti-inflammatory butyrate producer. Worse ADLs/IADLs and greater fatigability was associated with Clostridium innocuum, a commensal gut bacteria with documented potential for virulence. These results identify microbial species for further analysis in association with other‘omics layers and for future functional studies to understand their potential mechanistic effects on frailty and functioning outcomesin older adults.","cbCaijI2QVOEANts","https://ap.wps.com/l/cbCaijI2QVOEANts","pdf",2289527,"English","# Abstract\n## Study aim and data source\n## Microbial diversity associations\n## Species linked to frailty and function\n## Implications for future research","[{\"question\":\"What dataset and study design were used to analyze gut microbiome signatures?\",\"answer\":\"The study used data from the Integrative Longevity Omics (ILO) ongoing cohort, including 418 shotgun metagenomics samples from centenarians and their offspring.\"},{\"question\":\"How were gut microbiome features related to frailty and functional measures?\",\"answer\":\"Associations were tested between microbial alpha/beta diversity and species with function measures (ADLs and IADLs) and Fried frailty phenotype domains, including physical activity, fatigability, grip strength, and weight loss.\"},{\"question\":\"Which microbial species were identified as linked to better versus worse outcomes?\",\"answer\":\"Anareostipes hadrus was associated with improved ADLs and IADLs, lower fatigability, and reduced likelihood of substantial weight loss. Clostridium innocuum was associated with worse ADLs/IADLs and greater fatigability.\"}]","GUT MICROBIAL SIGNATURES OF FRAILTY AND FUNCTIONAL INDEPENDENCE IN CENTENARIANS AND OLDER ADULTS | PDF",1790640143]