Age-associated gut dysbiosis drives inflammaging — chronic low-grade inflammation — through gut barrier dysfunction, increased intestinal permeability, and immune activation via translocated microbial metabolites and endotoxins. This review synthesizes evidence that nonhuman primates (NHPs), specifically marmosets and macaques, share greater gut microbial taxonomic overlap and parallel age-associated microbial trajectories with humans than rodent models do, making them more valid translational platforms for mechanistic aging research. Pulmonary and other tissue microbiomes also undergo age-related shifts that may feed systemic and neuroinflammatory pathways — an underexplored dimension.
The core argument here is methodological rather than discovering new biology, but its implications are substantial. Rodent microbiomes diverge enough from human composition that interventions validated in mice routinely fail clinical translation — a persistent crisis in longevity research. NHP models, permitting controlled dietary, environmental, and infectious manipulation over lifespan, could finally allow causality to be established where only correlation currently exists. That said, this is a review paper synthesizing existing comparative data, not generating new experimental findings; the actual causal architecture linking dysbiosis to inflammaging in primates remains unresolved. Critical gaps — small cohort sizes, absent longitudinal datasets, non-standardized multi-omic pipelines — mean NHP research is promising but far from definitive. For adults, the practical implication is that microbiome-targeted healthspan interventions remain premature until this translational gap is properly closed through coordinated primate longitudinal studies.
