The association between gut microbiota and accelerated aging and frailty: a Mendelian randomization study

The recent observational studies have unveiled the correlation between the composition and dynamic alterations of the gut microbiome and aging; however, the causal relationship remains uncertain.

The objective of this study is to investigate the causal relationship between the gut microbiome and accelerated aging as well as frailty, from a genetic perspective.

We obtained data on the gut microbiome, intrinsic epigenetic age acceleration, and Frailty Index from published large-scale genome-wide association studies. A two-sample Mendelian randomization analysis was conducted primarily using inverse variance weighting model. We utilized the MR-Egger intercept analysis, IVW method, the Cochran Q test, and the leave-one-out analysis to assess the robustness of the results.

IVW analysis indicated a potential association between Peptococcus (OR: 1.231, 95% CI 1.013-1.497, P = 0.037), Dialister (OR: 1.447, 95% CI 1.078-1.941, P = 0.014) and Subdoligranulum (OR: 1.538, 95% CI 1.047-2.257, P = 0.028) with intrinsic epigenetic age acceleration; while Prevotella 7 (OR: 0.792, 95% CI 0.672-0.935, P = 0.006) was associated with a potential protective effect. Allisonella (OR: 1.033, 95% CI 1.005-1.063, P = 0.022), Howardella (OR: 1.026, 95% CI 1.002-1.050, P = 0.031) and Eubacterium coprostanoligenes (OR: 1.037, 95% CI 1.001-1.073, P = 0.042) were associated with an increased risk of frailty; conversely, Flavonifractor (OR: 0.954, 95% CI 0.920-0.990, P = 0.012) and Victivallis (OR: 0.984, 95% CI 0.968-1.000, P = 0.049) appeared to exhibit a potential protective effect against frailty.

The findings of this study provide further evidence for the genetic correlation between gut microbiota and accelerated aging as well as frailty, enhancing the understanding of the role of gut microbiota in aging-related processes. However, the underlying mechanisms and potential clinical applications require further investigation before any targeted interventions can be developed.