Gut microbiota-derived metabolites as immune modulators in aging and age-related chronic inflammatory diseases.

Nan Chen, Carmen K Chan, Farhan Ullah Khan, Priya Makhijani, Taylor R Valentino, Shawn Winer, Cynthia T Luk, Daniel A Winer

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, M5S 1A8, Canada; Division of Cellular & Molecular Biology, Diabetes Research Group, Toronto General Hospital Research Institute (TGHRI), University Health Network, Toronto, ON, M5G 1L7, Canada; Banting and Best Diabetes Centre, University of Toronto, Toronto, ON M5G 2C4, Canada. · pubmed

Paper

Abstract

Age-associated dysbiosis, marked by shifts in the composition of gut microbiota and gut microbiota-derived metabolites (GMDMs), is increasingly implicated in driving systemic low-grade inflammation during aging. The disrupted GMDM pools, including altered levels of short-chain fatty acids (SCFAs), secondary bile acids (BAs) and tryptophan (Trp) metabolites, lead to mucosal barrier dysfunction, immunometabolic dysregulation, and modulation of innate and adaptive immune cells. In turn, this cascade of events drives tissue degeneration, chronic inflammation, and the onset of age-related diseases (ARDs). Here, we summarize the immunomodulatory role of major GMDMs and how aging may increase susceptibility to ARDs through changing GMDMs. We then explore the latest findings linking altered GMDM profiles to immune dysfunction across major gut-organ axes, including the liver, adipose tissue, muscle, and brain. Last, we highlight recent advances in harnessing GMDMs as geromedicine to improve aging parameters and discuss the potential of artificial intelligence (AI) in accelerating the bench-to-bedside translation of GMDM research. Together, this review positions GMDMs as actionable targets in a dysbiosis-driven network of immune aging, offering new possibilities for the development of healthspan-extending precision geromedicine.

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Research summary

The paper claims that gut microbiota-derived metabolites (GMDMs) play a crucial role in modulating immune responses and may influence the onset of age-related diseases through dysbiosis. This research is relevant as it addresses the underlying mechanisms of aging and chronic inflammation, proposing GMDMs as potential targets for interventions aimed at extending healthspan.

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