Causal relationships between gut microbiome and hundreds of age- related traits: evidence of a replicable effect on ApoM protein levels

In the past 20 years, the involvement of gut microbiome in human health has received particular attention, but its contribution to age-related diseases remains unclear. To address this, we performed a comprehensive investigation of 4,033 potential causal relationships between 37 traits representing gut microbiome composition and function and 109 age-related phenotypes, using two-samples Mendelian randomization. Five causal relationships remained significant after multiple testing correction and sensitivity analyses, specifically between two taxa of Coriobacteriales and the risk of developing age-related macular degeneration, species Bifidobacterium adolescentis and levels of TNFSF12 protein in plasma, and the lactose-galactose degradation microbial I pathway and levels of IL-15Rα and TRAIL proteins in plasma. The causal relationship between the lactose-galactose degradation I pathway and TRAIL protein levels was further confirmed using independent data. These results support the role of gut microbiome in regulating the inflammatory circuit, albeit future studies are needed to investigate the underlying biological mechanisms.