Specific gut microbes are associated with the incidence of cardiometabolic disease in the HELIUS cohort

Associations between the gut microbiota and cardiometabolic health are well established, but evidence from longitudinal studies remains limited. In the prospective multi-ethnic HELIUS cohort, we investigated whether baseline gut microbiota composition was associated with long-term cardiometabolic outcomes. Fecal samples from 4792 participants were collected at baseline and analyzed using 16S rRNA sequencing. At follow-up, new diagnoses of hypertension, dyslipidemia, and diabetes were assessed, and major adverse cardiovascular events (MACE and MACE + , including angina pectoris) were obtained from hospital and mortality registries. Logistic regression was used to study associations with incident cardiometabolic disease, while Cox regression evaluated associations with MACE among participants without cardiovascular disease at baseline. During follow-up, 129 participants experienced MACE (2.7%) and 180 MACE+ (3.8%). Higher abundance of Eubacterium xylanophilum group spp. and Akkermansia muciniphila was associated with lower MACE+ risk, whereas Ruminococcus gnavus group spp. was associated with higher MACE risk, although only Eubacterium xylanophilum group spp. remained significant after full adjustment. Several taxa were associated with incident cardiometabolic disease, and exploratory metabolomics linked Ruminococcus gnavus group spp. to bile acid and acylcarnitine metabolites. These findings suggest that gut microbiota composition is longitudinally associated with cardiometabolic disease.