Association between gut microbiome profiles and host metabolic health across the life course: a population-based...

The human gut microbiome changes considerably over time. Previous studies have shown that gut microbiome profiles correlate with multiple metabolic traits. As disease development is likely a lifelong process, evidence gathered at different life stages would help gain a better understanding of this correlation. Therefore, we aim to investigate how the association of the gut microbiome and metabolic traits change over the lifespan.

We identified microbiome patterns (clusters) within two population-based cohorts at different life stages, i.e., pre-adolescents of the Generation R Study (mean age 9.8 years; n = 1488) and older adults of the Rotterdam Study (RS, mean age 62.7 years; n = 1265) using K-Means clustering, and surveyed for host metabolic phenotypes, lifestyles and other factors driving these patterns. Analyses were replicated in the Lifelines-DEEP Study (mean age 45.0 years; n = 1117). The association between microbiome clusters and host metabolic health was evaluated as well as the link between microbiome clusters and incident atherosclerotic cardiovascular disease (ASCVD) in RS during follow-up (median 6.5 years).

We identified two distinct microbiome clusters (U and H) within each study population presenting contrasting metabolic statuses. Cluster U was characterized by lower microbiome diversity, increased Streptococcus, Fusicatenibacter, and decreased Prevotella_9 and Christensenellaceae_R-7_group; wherein individuals showed higher fat percentage, triglycerides, use of medications, and lower socioeconomic status. Individuals in cluster U had increased odds (between 1.10 and 1.65) of being relatively metabolically unhealthy and presented a higher 5-year ASCVD risk (mean risk 0.059 ± 0.071 vs 0.047 ± 0.042, p < 0.001).

We provide evidence of a life-course relationship between gut microbiome profiles and metabolic health.

R.L is supported by European UnionHorizon 2020 research and innovation program under Marie Skłodowska-Curie grant agreement No 860898 [FIDELIO].