Gut microbiota as a causal mediator linking inflammatory cytokines and ageing phenotypes

Population ageing is a global phenomenon with significant implications for public health. Research has highlighted a relationship between gut microbiota, inflammatory cytokines, and ageing, yet the underlying causal mechanisms remain elusive. This study uses Mendelian randomization (MR) analysis to investigate causal relationships between gut microbiota, inflammatory cytokines, and ageing phenotypes. We leveraged the summary statistics of gut microbiota (n = 5959), circulating inflammatory cytokines (n = 8293), and three ageing phenotypes including telomere length (n = 472,174), facial ageing (n = 423,999), and frailty index (n = 175,226). We performed bidirectional MR analyses to explore the causal effects of gut microbiota and inflammatory cytokines on ageing, and mediation analyses to discover potential mediating gut microbiota and inflammatory cytokines. Our findings suggest that there are causal interactions between gut microbiota, inflammatory cytokines, and ageing. Notably, the abundance of GCA-900066575 sp900066385 appears to mediate the M-CSF pathway to facial ageing. The current MR study provides evidence supporting causal relationships between inflammatory cytokines and ageing and potential mediating gut microbiota, which are critical to advancing our understanding of the ageing process and developing effective interventions.