Networks of gut bacteria relate to cardiovascular disease in a multi-ethnic population: the HELIUS study

Abstract Aims Gut microbiota have been linked to blood lipid levels and cardiovascular diseases (CVD). The composition and abundance of gut microbiota trophic networks differ between ethnicities. We aim to evaluate the relationship between gut microbiotal trophic networks and CVD phenotypes. Methods and Results We included cross-sectional data from 3860 individuals without CVD history from six ethnicities living in the Amsterdam region participating in the prospective Healthy Life in Urban Setting (HELIUS) study. Genetic variants were genotyped, fecal gut microbiota were profiled and blood and anthropometric parameters were measured. A machine learning approach was used to assess the relationship between CVD risk (Framingham Score) and gut microbiota stratified by ethnicity. Potential causal relationships between gut microbiota composition and CVD were inferred by performing two sample Mendelian randomization with hard CVD events from the Pan-UK biobank and microbiome GWAS summary data from a subset of the HELIUS cohort (n = 4117). Microbial taxa identified to be associated with CVD by machine learning and Mendelian randomization were often ethnic specific, but some concordance across ethnicities was found. The microbes Akkermansia muciniphila and Ruminococcaceae UCG-002 were protective against ischemic heart disease in African Surinamese and Moroccans, respectively. We identified a strong inverse association between blood lipids, CVD risk and the combined abundance of the correlated microbes Christensenellaceae-Methanobrevibacter-Ruminococcaceae (CMR). The CMR cluster was also identified in two independent cohorts and the association with triglycerides was replicated. Conclusions Certain gut microbes can have a potentially causal relationship with CVD events, with possible ethnic specific effects. We identified a trophic network centered around Christensenellaceae, Methanobrevibacter and various Ruminococcaceae, frequently lacking in South-Asian Surinamese, to be protective against CVD risk and associated with low triglyceride levels.