[Figure 1]. The bidirectional relationship between the gut microbiome and aging.

(Left panel) In a healthy gut, balanced microbial composition and intestinal barrier integrity maintains gut homeostasis and contains the microbiota in the intestinal lumen. Microbiota-derived metabolites, including SCFAs, participate in a feedback mechanism with the host immune system to fortify the barrier function, produce mucus and promote intestinal stem cell proliferation. An efficient immune system tolerates the host immune responses to avoid excessive activation. (Right panel) In gut dysbiosis (such as with aging), declined intestinal barrier integrity results in translocation of microbes and microbial particles through the intestinal epithelial cell lining. Reduced microbiota diversity leads to overgrowth of distinct microbes and metabolism instability. Aberrant levels of microbiota-derived metabolites instigate abnormal immune responses resulting in chronic inflammation. SCFA: Short-chain fatty acid.