Biochem Pharmacol. 2026 Jul 19:118267. doi: 10.1016/j.bcp.2026.118267. Online ahead of print.
ABSTRACT
The human colonic microbiota has been estimated to contain 38 trillion bacteria whereas the total human somatic cells constitute 30 trillion. The mutualistic relationship between host and microbiome is ancient and believed to have evolved over 600 million years ago. Other than a digestive function and provision to the host of certain vitamins, the gut microbiome has a single important and overarching purpose, which is maintenance of homeostasis by regulation of host metabolism and immune function. Consuming a diet that maintains gut microbial eubiosis and avoids dysbiosis is essential for a long healthy life. Dysbiosis contributes to noncommunicable illnesses, including hypertension, cardiovascular disease, obesity, diabetes, inflammatory bowel disease, and cancer, any of which can reduce lifespan. The combined impact of diabetes and heart disease alone potentially shortens lifespan by up to 15-23 years. Although there has been considerable research on the bacterial abundance and diversity of the human gut microbiota, relatively little detailed attention has been given to the metabolites it produces, especially in relation to morbidity and mortality. By a thorough analysis of the gut bacterial species associated with longevity, we have identified a number of their metabolites that are beneficial to the host in this regard. The action of these metabolites underlines an important principle - that what is generated by the intestinal microbiota from a wholesome diet determines healthy aging and ultimately longevity. Future research on gut microbiota function should focus on the detailed mechanisms of action of beneficial bacterial metabolites that prolong both healthspan and lifespan.
PMID:42472578 | DOI:10.1016/j.bcp.2026.118267