The microbiome of aging: instability, heterogeneity, and pathogenicity reservoirs in the skin, oral, and gut microbiome of older adults

While older adults represent a vulnerable population with elevated risk for numerous chronic illnesses, the role played by the microbiome in such age-related susceptibilities remains largely unexplored. Stereotypical changes in physiological and immune responses with aging likely contribute to microbiome-related increases in predisposition to common late life diseases. To understand associations of the microbiome with age, frailty, and infectious disease risk factors, we conducted a longitudinal, whole genome shotgun study of the skin, oral, and gut microbiota in 47 older adults residing in community or skilled nursing facility (SNF) settings. We found prominent differences in microbiomes from all body sites between younger adults, older adults living in the community, and SNF residents. In addition, frailty correlated negatively with relative abundance of Cutibacterium (C.) acnes in the skin microbiome, which itself strongly correlated with decreased microbial community stability and increased diversity, heterogeneity, and biogeographic determinism, factors that have been associated with susceptibility to pathogen colonization and disease risk. Strikingly, the skin microbiota, rather than gut or oral communities, was the primary reservoir for plasmid-borne antimicrobial resistance and clinically important pathobionts. Strain composition of important commensal species such as C. acnes and Staphylococcus epidermidis in SNF residents further suggested a shift from healthy to pro-inflammatory and nosocomial strains. Our findings set the foundation for understanding relative risk of microbiome-mediated frailty and disease processes in older adults in different residential settings, and for the development of strategies to leverage the microbiota as tools to promote healthy aging, disease prevention, and to limit the dissemination of multidrug resistant pathogens.