A Chinese cohort study suggested a causal effect of gut microbiota on non-HDL-c and identified 3-indolepropionic acid and N-methyltryptamine as key effectors of gut microbiota to the variation of non-high-density lipoprotein cholesterol (non-HDL-c). The study included a total of 1361 community-dwelling participants without major diseases and free of antibiotics and lipid-lowering therapies. Fecal metagenomics, plasma metabolomics and host genotyping showed that decreased Eubacterium rectale but increased Clostridium sp CAG_299 were causally linked to a higher level of non-HDL-c. A total of 16 microbial capacities were found to be independently associated with non-HDL-c after adjusting for age, sex, demographics, lifestyles, and comorbidities, with the strongest association observed for tricarboxylic acid (TCA) cycle. Moreover, the integration of multi-omics and bi-directional mendelian randomization analysis revealed that decreased 3-indolepropionic acid and N-methyltryptamine, resulting from suppressed capacities for microbial reductive TCA cycle, functioned as major microbial effectors to the elevation of circulating non-HDL-c. The findings are in line with previous studies and highlight the potential of targeting gut microbiota to control non-HDL-c. Non-HDL-c is a strong risk factor for incident cardiovascular diseases. There is a substantial influence of genetic backgrounds, diet, lifestyles, and geographic differences on gut microbiota that has been implicated in the regulation of host metabolism. Source: https://www.thelancet.com/
