Gut microbiome pattern reflects healthy aging and predicts survival in humans

The gut microbiome has important effects on human health, yet its importance in human aging remains unclear. Here we demonstrate that, starting in mid-to-late adulthood, gut microbiomes become increasingly unique to individuals with age. We leverage three independent cohorts comprising over 9000 individuals and find that compositional uniqueness is strongly associated with microbially produced amino acid derivatives circulating in the bloodstream. In older age (over ~80 years), healthy individuals show continued microbial drift toward a unique compositional state, whereas this drift is absent in less healthy individuals. The identified microbiome pattern of healthy aging is characterized by a depletion of core genera found across most humans, primarily Bacteroides. Retaining a high Bacteroides dominance into older age, or having a low gut microbiome uniqueness measure, predicts decreased survival in a four-year follow-up. Our analysis identifies increasing compositional uniqueness of the gut microbiome as a component of healthy aging, which is characterized by distinct microbial metabolic outputs in the blood.