Abstract

Stem cells and the microbiome coexist in interdependent systems essential for tissue development, regeneration and homeostasis. Dysbiosis and aging both interfere with the stem cell-microbiome axis, resulting in stem cell depletion and tissue degeneration. This short review elucidates the mechanistic basis of microbiome-stem cell interactions, describing how microbial metabolites-such as short-chain fatty acids, bile acids, vitamins and tryptophan derivatives-influence stem cell quiescence and regulate proliferation, differentiation and epigenetic programming through nutrient-sensing pathways, including AMPK-mTOR, NAD⁺/SIRT1 and FXR/TGR5. New research shows that bringing microbial balance back or adding microbiome-and metabolite-based factors can make old stem cells younger and improve the ability of an organ to regenerate in a specific way. Taken together, targeting the microbiome-stem cell axis is a new and promising way to improve healthspan and slow down the effects of aging. This review offers an integrative synthesis of mechanistic and metabolic perspectives, highlighting opportunities for precision regenerative and microbiome-based interventions to promote healthy aging.

Keywords: Microbiome stem cells; Aging regeneration; Dysbiosis; Short-chain fatty acids; Epigenetics; Healthspan; Personalized healthcare