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Background  Acetate is a short-chain fatty acid (SCFA) produced by gut bacteria, which has been implicated in cardio-metabolic health. Here we examine the relationships of circulating acetate levels with gut microbiome composition and diversity and with visceral fat in a large population-based cohort.    Results  Microbiome alpha-diversity was positively correlated with circulating acetate levels (Shannon, Beta [95%CI] = 0.12 [0.06, 0.18],  P  = 0.002) after adjustment for covariates. Six serum acetate-associated bacterial genera were also identified, including positive correlations with  Coprococcus ,  Barnesiella ,  Ruminococcus , and  Ruminococcaceae NK4A21  and negative correlations were observed with  Lachnoclostridium  and  Bacteroides.  We also identified a correlation between visceral fat and serum acetate levels (Beta [95%CI] = −0.07 [−0.11, −0.04],  P  = 2.8 × 10 –4 ) and between visceral fat and  Lachnoclostridium  (Beta [95%CI] = 0.076 [0.042, 0.11],  P  = 1.44 × 10 –5 ). Formal mediation analysis revealed that acetate mediates ∼10% of the total effect of  Lachnoclostridium  on visceral fat. The taxonomic diversity showed that  Lachnoclostridium  and  Coprococcus  comprise at least 18 and 9 species, respectively, including novel bacterial species. By predicting the functional capabilities, we found that  Coprococcus  spp. present pathways involved in acetate production and metabolism of vitamins B, whereas we identified pathways related to the biosynthesis of trimethylamine (TMA) and CDP-diacylglycerol in  Lachnoclostridium  spp.    Conclusions  Our data indicates that gut microbiota composition and diversity may influence circulating acetate levels and that acetate might exert benefits on certain cardio-metabolic disease risk by decreasing visceral fat.  Coprococcus  may play an important role in host health by its production of vitamins B and SCFAs, whereas  Lachnoclostridium  might have an opposing effect by influencing negatively the circulating levels of acetate and being involved in the biosynthesis of detrimental lipid compounds.

Circulating Levels of the Short-Chain Fatty Acid Acetate Mediate the Effect of the Gut Microbiome on Visceral Fat