Dietary Index for Gut Microbiota, Plasma Metabolic Signature, and Risk of All-Cause and Cardiovascular Disease...

The dietary index for gut microbiota (DI-GM) and its associations with mortality risk, as well as the underlying mechanisms, remain underexplored. We aimed to investigate the associations among DI-GM, a corresponding metabolic signature, and all-cause and cardiovascular disease (CVD) mortality.

We analysed two cohort studies including 170,575 participants from the United Kingdom (UK) Biobank and 26,651 participants from the United States (US) National Health and Nutrition Examination Survey. We calculated DI-GM using 24-hour dietary recall questionnaire data and derived a corresponding metabolic signature using an elastic net regression model. Associations were assessed using Cox proportional hazards regression.

Participants in the highest DI-GM group had a lower risk of all-cause mortality (hazard ratio [HR], 0.86, P<0.001 in the UK cohort; HR, 0.79, P<0.001 in the US cohort) and CVD mortality (HR, 0.79, P=0.013 in the UK cohort; HR, 0.68, P=0.007 in the US cohort) than those in the lowest group. Both overall DI-GM and foods beneficial for gut microbiota were inversely associated with mortality risk in a dose-response manner. We identified a DI-GM metabolic signature comprising 124 metabolites in the UK cohort (r=0.25, P<2.2×10-16); this signature was associated with the risk of all-cause mortality (HR, 0.68, P<0.001) and CVD mortality (HR, 0.65, P=0.003) and explained 52.60% of the association between DI-GM and all-cause mortality.

We identified a close connection between DI-GM, its metabolic signature, and mortality outcomes, highlighting the potential benefits of dietary patterns that support gut microbiota health for longevity.