Julia Oh of The Jackson Laboratory.
We humans tend to think we live independently, capable of ensuring our own health and wellbeing. As researchers are increasingly aware, however, our microbiomes—the trillions of microbes that live on and within us—play central roles in our health and susceptibility to different diseases. And as we age, our microbiomes change too, with important health implications over time.
Because of the unique design of their study, where they sampled frail older adults inhabiting skilled nursing facilities as well as community-dwelling older adults, they found that the greatest microbiome differences between the groups were associated with increased frailty, not chronological age. A second surprising finding was that microbiome differences between cohorts were most pronounced in the skin, rather than the gut or mouth. Moreover, the skin harbored the greatest number of potential risk factors for infectious disease. The researchers presented their findings in “Associations of the skin, oral and gut microbiome with aging, frailty and infection risk reservoirs in older adults,” published in Nature Aging.
Microbiomes across the years
The researchers worked with one group of older adults—65 years old or older—who live in skilled nursing facilities, and with another matched group who live independently in the community. In all, they collected a total of 1,385 samples (1,072 skin, 159 oral, 154 stool (gut)) from 47 individuals at three time points over a month. They compared these with matched samples from 95 healthy younger (18-55) adults. In addition, at each visit, the researchers collected detailed medical histories, conducted dietary and hygiene surveys, and assessed frailty using standard clinical methods. By using advanced metagenomic sequencing and algorithms to reconstruct the microbiome, they achieved the resolution needed to identify pathogenic species and sub-strains, antibiotic resistance genes and virulence factors.
The most prominent difference at all body sites occurred in the frail older adults dwelling in nursing facilities. Broad community differences, such as the diversity and stability of the microbiome—perhaps reflecting the differences in how individuals age—were observed. These factors have been broadly associated with disease susceptibility and infection risk. In addition, they used machine learning tools to identify potential microbial biomarkers of aging and frailty. For example, in the gut, the frail older adults had a significantly higher proportion of Clostridium species and changes in the proportions of major bacterial phyla that have been associated with obesity and dietary differences. In the skin, the younger cohort had substantial and consistent prevalence of C. acnes in oily areas, which is a keystone skin microbe that regulates a healthy skin environment. C. acnes was depleted in both older cohorts, with some of the species that became enriched in the facility cohort associated with increased infection risks.
Frailty and microbes
Interestingly, when the research team assessed a variety of microbiome characteristics, including species composition, stability, diversity, and more, chronological age alone did not associate with any of them. On the other hand, the relative abundance or presence of a number of bacterial species on the skin significantly correlated with frailty. Importantly, the skin of the frail older adults was enriched in clinically important, potentially pathogenic species as well as antibiotic resistance genes, which can contribute to resistance to common antibiotics. It is of note that the skin microbiome, compared with the more numerous oral and gut microbiota, thus emerged as the primary reservoir for infection risk associated with frailty.
“This work advances our understanding of frailty, an aging-related syndrome of physiological decline, characterized by marked vulnerability to adverse health outcomes,” says Kuchel.
Taken together, the findings call attention to the skin as a potential beacon for general declines in the health status of older adults. In fact, the authors suggest defining a Frailty-Associated Dysbiosis of the Skin (FADS) based on microbiome instability and divergence of microbial proportions between different areas on the body. The concept could inform future studies that seek to better understand how FADS and other factors can increase disease risk for older adults.
“This was an extraordinary multidisciplinary effort between our clinical and research team at UConn Center on Aging and The Jackson Laboratory for Genomic Medicine,” says Oh. “We believe this exciting study is an important step to understanding how the microbiome contributes to aging and chronic diseases, in turn allowing us to identify potential interventional targets to improve health across lifespan.”