AUTHOR=Nogal Ana , Louca Panayiotis , Zhang Xinyuan , Wells Philippa M. , Steves Claire J. , Spector Tim D. , Falchi Mario , Valdes Ana M. , Menni Cristina 

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

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.711359

DOI=10.3389/fmicb.2021.711359

ISSN=1664-302X

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Results</title><p>Microbiome alpha-diversity was positively correlated with circulating acetate levels (Shannon, Beta [95%CI] = 0.12 [0.06, 0.18], <italic>P</italic> = 0.002) after adjustment for covariates. Six serum acetate-associated bacterial genera were also identified, including positive correlations with <italic>Coprococcus</italic>, <italic>Barnesiella</italic>, <italic>Ruminococcus</italic>, and <italic>Ruminococcaceae NK4A21</italic> and negative correlations were observed with <italic>Lachnoclostridium</italic> and <italic>Bacteroides.</italic> We also identified a correlation between visceral fat and serum acetate levels (Beta [95%CI] = −0.07 [−0.11, −0.04], <italic>P</italic> = 2.8 × 10<sup>–4</sup>) and between visceral fat and <italic>Lachnoclostridium</italic> (Beta [95%CI] = 0.076 [0.042, 0.11], <italic>P</italic> = 1.44 × 10<sup>–5</sup>). Formal mediation analysis revealed that acetate mediates ∼10% of the total effect of <italic>Lachnoclostridium</italic> on visceral fat. The taxonomic diversity showed that <italic>Lachnoclostridium</italic> and <italic>Coprococcus</italic> comprise at least 18 and 9 species, respectively, including novel bacterial species. By predicting the functional capabilities, we found that <italic>Coprococcus</italic> 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 <italic>Lachnoclostridium</italic> spp.</p></sec><sec><title>Conclusions</title><p>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. <italic>Coprococcus</italic> may play an important role in host health by its production of vitamins B and SCFAs, whereas <italic>Lachnoclostridium</italic> might have an opposing effect by influencing negatively the circulating levels of acetate and being involved in the biosynthesis of detrimental lipid compounds.</p></sec>