Gut Check: The Impact of Gut Bacteria on Physical Function in Older Adults with and without HIV

. Physical function refers to an individual's ability to perform daily tasks and activities and is a crucial aspect of overall health. Maintenance of physical function is the cornerstone of successful aging with declines in physical function associated with increased risk of hospitalization, institutionalization, and premature mortality. We and others have shown that chronic diseases, including HIV, can significantly accentuate the decline of physical function. The gut microbiome plays a pivotal role in the regulation of gut health. Alterations in gut microbial communities (dysbiosis) accompany physiological aging and emerging evidence illustrate links between the gut microbiome and physical function and frailty in older people without HIV. HIV-associated dysbiosis has been reported to be among the strongest disease-associated dysbioses, and associations between the gut microbiome and multiple aging outcomes in PWH have been observed. In a recent study of sedentary older people with and without HIV, we found that HIV serostatus modified the fecal microbiome, such that those with HIV had a unique microbiome with increasing age. Emphasizing the clinical relevance of these findings in a subsequent pilot study, we observed associations between gut bacterial abundance and physical function that differed between older people with and without HIV, highlighting the need to understand these relationships in different disease states. We recently explored associations between frailty and gut microbiome within the MACS/WIHS Combined Cohort Study (MWCCS), a large nationwide, ongoing observational cohort. Differences by age among both men and women with and without HIV were noted; importantly, specific genera were associated with lower or greater odds of frailty, a composite measure indicative of vulnerability with aging. Frailty is a broad syndrome and recognizing gut microbiome relationships to specific measures of physical function will provide greater specificity as to potential mechanisms. Moreover, understanding both bacteria abundance and functional output are needed to properly appreciate the complex relationship between gut bacteria imbalances and physical function. To investigate our central hypothesis that HIV- and age-induced gut dysbiosis is associated with physical function impairments, we will evaluate relationships between fecal bacteria abundance and functional potential with physical function using data collected as part of the MWCCS. We will first evaluate cross-sectional relationships (Aim 1) and then determine if gut microbiome patterns predict changes in physical function over time (Aim 2). The knowledge gained from this well-powered investigation into the gut- physical function axis will promote the development of effective population-specific, strategically designed and cost-effective adjunct microbiome-based therapies to prevent or reverse physical function impairments among older adults, including those with HIV who experience age-associated decline in physical function at an earlier age. Project Number: 1R03AG094334-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute on Aging (NIA) | Principal Investigator: Stephanie Dillon | Institution: UNIVERSITY OF COLORADO DENVER, Aurora, CO | Award Amount: $156,000 | Activity Code: R03 | Study Section: Special Emphasis Panel[ZRG1 IIDB-J (03)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11327529