Gut microbiota dynamics, exercise and physical function among older people with HIV

University Of Colorado Denver, Aurora CO

Investigators

Abstract

PROJECT SUMMARY. Novel strategies are urgently needed to enhance the efficacy of exercise in improving physical function of older people with HIV (PWH). Our team has identified impairments in measures of physical function across several cohorts of middle-aged and older PWH. Exercise is the standard of care for prevention and treatment of impaired physical function in people without HIV, and we previously demonstrated that exercise also improves physical function in older PWH; however, the effectiveness of responses varied. The gut microbiome plays a pivotal role in the regulation of gut health, and exercise has been associated with changes in the gut microbiome and improvements in physical function measures in people without HIV, yet little is known in regards to the gut microbial features associated with an exercise-gut microbiome-physical function axis in older PWH. HIV-1- associated disruption of the gastrointestinal tract is characterized by perturbations in gut microbiota (dysbiosis), epithelial barrier breakdown and microbial translocation which, in turn, has been linked to systemic inflammation and the development of multiple age-associated co-morbidities. In our prior studies of older adults with and without HIV, we established that relationships between the gut microbiome and relevant outcomes (systemic inflammation, physical function) differ based on HIV serostatus. Moreover, systemic levels of intestinal fatty acid binding protein (IFABP), a biomarker indicative of gut epithelial barrier damage, were reduced in older PWH following an exercise intervention. In preliminary studies, we found that in older PWH, higher levels of myostatin, a muscle biomarker associated with the negative regulation of skeletal muscle growth, significantly associated with higher systemic levels of IFABP, and myostatin levels were reduced following a supervised exercise intervention. Similar observations were not observed in people without HIV. Taken together, our observations suggest a unique exercise-gut microbiome-physical function axis also exists in older PWH. The central hypothesis of this proposal is that a supervised exercise intervention will lead to changes in the gut microbiome of older PWH with associated improvements in gut epithelial barrier integrity and reduced microbial translocation, ultimately resulting in improved muscle function and physical function outcomes. These ‘health-positive’ changes in the microbiome will be observed to a lesser extent (if at all) in participants with limited improvements in physical function. We propose to determine the impact of a 16 week supervised exercise intervention on the structure and function of fecal microbial communities in older PWH with viral suppression (Aim 1), and to identify microbial and metabolomic features associated with epithelial barrier damage, microbial translocation and muscle health (Aim 2), and with physical function outcomes (Aim 3). Identification of specific gut microbiome features will provide the groundwork for the effective design of future therapeutic trials that enhance the efficacy of exercise in improving physical function of older PWH.