Association between Prevalent Flagellated Bacteria in Gut Microbiota and Cardiovascular Benefits in Humans

Abstract Background Increasing evidence has shown associations between gut microbiota and cardiovascular risks. However, whether sex influences the cardiovascular outcome of gut microbiota remains elusive. Methods The gut microbiota metagenomic data from two previous population-based cohorts and the proteomics data from human liver samples were analyzed. Results Through a sex-based analysis of 500 Functional Genomics Project (500FG) cohort, we found that the capacity of producing flagellin in Eubacterium rectale, Roseburia Intestinalis and Roseburia inulinivorans partially explained the levels of high-density lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 in female participants. By comparing the bacterial species showing positive correlations with HDL-C and the flagellin species found in human liver samples, we found that E. rectale and R. inulinivorans appeared to be the major prevalent flagellated species in gut microbiota contributed to the host’s HDL-C level. The analysis of the Chinese-based cohort in which the male participants had relatively higher abundance of these two bacteria, the abovementioned positive correlation was also observed. Conclusions The flagellin-producing function of E. rectale and R. inulinivorans in the gut microbiota partially explained the HDL-C level in the host, and there is a sex-specific difference in the sensitivity of this beneficial interaction. Our findings suggest a potential interaction between commensal bacteria and the host that yields a cardiovascular benefit. Clinical Perspective What is new? The flagellin-producing capacity of certain species in gut microbiota is positively associated with the HDL-C and ApoA1 levels in human. By comparing the flagellated bacteria in the gut and flagellin species in the liver, Eubacterium rectale and Roseburia inulinivorans are shown to be the most prevalent species contributing to such cardiovascular benefits. The sensitivity of such beneficial interaction with the gut flagellated bacteria is different between male and female. What are the clinical implications? (maximum 100 words, formatted as 2-3 bullets) Beside the role in metabolic inflammation, gut microbiota can be beneficial against cardiovascular risk by modulating HDL-C level through certain flagellated species. The interaction between flagellated bacteria in the gut and the host provide a different insight in exploring potential therapeutic targets to increase HDL-C level.