Gut microbiome and aging—A dynamic interplay of microbes, metabolites, and the immune system

Aging is accompanied by profound changes in both the gut microbiome and the immune system, which engage in continuous, bidirectional communication. Alterations in microbial diversity and metabolism, particularly reductions in short-chain fatty acid (SCFA) producers as well as shifts in bile acid and tryptophan-metabolizing species, can incite and worsen inflammation, damage barrier integrity, and accelerate immunosenescence. Concomitantly, immune aging and reduced mucosal IgA promote microbial dysbiosis, forming a self-reinforcing cycle that fuels chronic inflammation ("inflammaging"). Microbial metabolites such as SCFAs, secondary bile acids, and indole derivatives play central roles in this gut-immune dialog, influencing regulatory T-cell balance, epithelial repair, and neurological health through the gut-brain axis. Emerging evidence suggests that diet, probiotics, postbiotics, and microbiome transplantations can restore beneficial microbial and, consequently, immune functions, offering opportunities to promote healthy aging and potentially reverse adverse symptoms. Understanding and targeting the gut microbiome-immune feedback loops may reveal new strategies to modulate inflammaging and extend health span.