Causal relationship between gut microbiota and ageing: A multi-omics Mendelian randomization study

Observational studies and clinical trials have suggested a connection between gut microbiota and aging. However, the causal relationship between them remains undetermined.

This study aimed to use bidirectional two-sample Mendelian randomization (TSMR) analysis to explore the causal relationship between gut microbiota and aging.

Summary statistics from genome-wide association studies (GWAS) on gut microbiota and seven aging-related phenotypes were employed for TSMR analysis. Reverse Mendelian randomization (MR) analysis was performed to assess the potential for reverse causality. Additionally, the relationship between Akkermansia muciniphila and inflammation-related proteins and metabolites was further investigated. The effects of Akkermansia muciniphila on aging were also examined in Caenorhabditis elegans by measuring both lifespan and healthspan.

MR analysis of 207 microbial taxa and seven aging phenotypes revealed 44 causal relationships between the gut microbiota and aging. Akkermansia muciniphila was found to be causally linked to several aging-related traits, including mvAge, appendicular lean mass, and grip strength (P < 0.05). Reverse MR analysis identified 23 causal relationships, but no bidirectional causality was observed. Moreover, Akkermansia muciniphila is causally related to ST1A1, taurine bile acid, and mannose (P < 0.05). In Caenorhabditis elegans, treatment with Akkermansia muciniphila significantly extended lifespan (P < 0.05) and improved mobility in aging nematodes.

TSMR analysis uncovers multiple potential causal links between gut microbiota and aging, particularly Akkermansia muciniphila. Experimental results support its role in alleviating aging. This study provides a strong foundation for future research on gut microbiota's role in aging.