The gut microbiome changes with age, and evidence suggests that this provides a meaningful contribution to degeneration and disease. Microbial populations that provoke chronic inflammation grow in size at the expense of populations that produce beneficial metabolites. Researchers here show that gut microbiome composition is a better predictor of the burden of inflammation and risk of disease than chronological age, much as one might expect given what is known of age-related changes in gut microbiome composition, and also given that researchers have built aging clocks from gut microbiome data. It is one more argument for a greater focus on the development and availability of therapeutic approaches capable of lasting rejuvenation of the gut microbiome, such as fecal microbiota transplantation and flagellin immunization.
Low-grade systemic inflammation increases with age and accompanies many age-associated lifestyle-related diseases, yet substantial inter-individual variability exists beyond chronological age. Given the gut microbiota's role in immune regulation, we analyzed paired fecal microbiota profiles, 30 plasma cytokines, and 19 biochemical and physiological measures in 1,199 adults (aged 20-72) from the population-based DanFunD cohort to assess the relative associations of microbiota composition and age with systemic inflammation and subsequent disease risk.
Here we show that despite an association between age and 40% of inflammatory cytokines and most physiological variables, gut microbiota composition explained more variance than age for 97% of cytokines and 84% of physiological variables. Individuals with the Bacteroides 2 enterotype exhibited elevated pro-inflammatory cytokines and adverse metabolic profiles already in early adulthood, displaying an inflammaging-like phenotype up to 37 years earlier than other enterotypes. This enterotype was associated with increased risk of future incident disease across multiple organ systems (hazard ratio 1.21), with mediation analyses suggesting that inflammatory cytokines accounted for part of this association. Conversely, a high-diversity enterotype was linked to lower inflammation and reduced disease risk.
These findings position gut microbiota composition as a stronger correlate of systemic inflammatory tone than chronological age and a potentially modifiable determinant of inflammation-related disease trajectories across adulthood.
Link: https://doi.org/10.1038/s41467-026-77499-9
View the full article at FightAging
