Correlations Between Gut Microbiome Composition and Longevity

A great deal of research is focused on cataloguing and correlating specific differences in the gut microbiome with aspects of aging. In years ahead, techniques will be developed to more precisely control the composition of the gut microbiome, removing issues such as too great a number of inflammatory microbes, or those producing harmful metabolites. At the moment, only more crude approaches such as fecal microbiota transplantation from a young donor are well developed. In principle it should be possible to take a probiotic approach and use oral administration to achieve a similar outcome, a rejuvenated gut microbiome, but the knowledge and logistics are still lacking when it comes to producing the desired combination of microbes at scale.

As a complex and dynamic ecosystem, the gut microbiota is associated with major conditions like obesity, type 2 diabetes, cardiovascular disease, and cancer. Associations between aging and gut microbiota have been well-studied. Several studies have suggested that aging is associated with the composition of the gut microbiome and its metabolites, primarily through nutrient signaling pathways, immune regulation mechanisms, and epigenetic mechanisms. Aging-related gut dysbiosis may lead to the occurrence or progression of other metabolic diseases, resulting in a loss of healthy longevity. In addition, aging-related diet patterns can influence gut microbiota health, and dietary interventions can improve intestinal health and immune status in older adults, thereby increasing their healthy longevity. However, the biological mechanism of gut microbiota affecting longevity-related traits, such as healthspan and longevity, remains elusive.

Our study explored the effect of gut microbiota on longevity based on the data from multiple independent large-scale genome wide association studies (GWAS) of gut microbiota and longevity. Findings from linkage disequilibrium score (LDSC) regression analysis indicate a suggestive genetic correlation between gut microbiota and longevity. Utilizing the independent GWAS data, we further tested the causal association between identified candidate gut microbiota and longevity-related traits using Mendelian Randomization (MR) analysis. Our results provided potential clues for the effect of gut microbiota on longevity.

LDSC analysis detected four candidate genetic correlations, including Veillonella (genetic correlation = 0.5578) and Roseburia (genetic correlation = 0.4491 for longevity, Collinsella (genetic correlation = 0.3144 for parental lifespan and Sporobacter (genetic correlation = 0.2092) for healthspan. Further MR analysis observed suggestive causation between Collinsella and parental longevity (father's age at death). Reverse MR analysis also detected several causal effects of longevity-related traits on gut microbiota, such as longevity and Sporobacter.