The Gut Microbiota and Unhealthy Aging: Disentangling Cause from Consequence

The gut microbiota changes with age, but it is not clear to what degree these changes are due to physiologic changes, age-associated inflammation or immunosenescence, diet, medications, or chronic health conditions. Observational studies in humans find that there are profound differences between the microbiomes of long-lived and frail individuals, but the degree to which these differences promote or prevent late-life health is unclear. Studies in model organisms demonstrate that age-related microbial dysbiosis causes intestinal permeability, systemic inflammation, and premature mortality, but identifying causal relationships have been challenging. Herein, we review how physiological and immune changes contribute to microbial dysbiosis and the degree to which microbial dysbiosis contributes to late-life health conditions. We discuss the features of the aging microbiota that make it more amenable to diet and pre- and probiotic interventions. Health interventions that promote a diverse microbiome could influence the health of older adults.