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Acetate reprograms gut microbiota during alcohol consumption.

ABSTRACT: Liver damage due to chronic alcohol use is among the most prevalent liver diseases. Alcohol consumption frequency is a strong factor of microbiota variance. Here we use isotope labeled [1-¹³C] ethanol, metagenomics, and metatranscriptomics in ethanol-feeding and intragastric mouse models to investigate the metabolic impacts of alcohol consumption on the gut microbiota. First, we show that although stable isotope labeled [1-¹³C] ethanol contributes to fatty acid pools in the liver, plasma, and cecum contents of mice, there is no evidence of ethanol metabolism by gut microbiota ex vivo under anaerobic conditions. Next, we observe through metatranscriptomics that the gut microbiota responds to ethanol-feeding by activating acetate dissimilation, not by metabolizing ethanol directly. We demonstrate that blood acetate concentrations are elevated during ethanol consumption. Finally, by increasing systemic acetate levels with glyceryl triacetate supplementation, we do not observe any impact on liver disease, but do induce similar gut microbiota alterations as chronic ethanol-feeding in mice. Our results show that ethanol is not directly metabolized by the gut microbiota, and changes in the gut microbiota linked to ethanol are a side effect of elevated acetate levels. De-trending for these acetate effects may be critical for understanding gut microbiota changes that cause alcohol-related liver disease.

SUBMITTER: Martino C

PROVIDER: S-EPMC9359997 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Acetate reprograms gut microbiota during alcohol consumption.

Martino Cameron C Zaramela Livia S LS Gao Bei B Embree Mallory M Tarasova Janna J Parker Seth J SJ Wang Yanhan Y Chu Huikuan H Chen Peng P Lee Kuei-Chuan KC Galzerani Daniela Domingos DD Gengatharan Jivani M JM Lekbua Asama A Neal Maxwell M Knight Rob R Tsukamoto Hidekazu H Metallo Christian M CM Schnabl Bernd B Zengler Karsten K

Nature communications 20220808 1

Liver damage due to chronic alcohol use is among the most prevalent liver diseases. Alcohol consumption frequency is a strong factor of microbiota variance. Here we use isotope labeled [1-<sup>13</sup>C] ethanol, metagenomics, and metatranscriptomics in ethanol-feeding and intragastric mouse models to investigate the metabolic impacts of alcohol consumption on the gut microbiota. First, we show that although stable isotope labeled [1-<sup>13</sup>C] ethanol contributes to fatty acid pools in the ...[more]

PMID: 35941112

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Project description:Background: Epidemiological studies confirmed that moderate alcohol consumption was associated with a reduced risk of adverse cardiovascular events. It is increasingly recognized that the composition of gut microbiota and metabolites is involved in modulating the cardiovascular health of the host. However, the association of moderate alcohol consumption with serum metabolites and gut microbiome and its impact on coronary artery disease (CAD) is not fully investigated. Method: Serum untargeted metabolomics analysis and fecal 16S rRNA sequencing were performed on 72 male patients with CAD having various alcohol consumption (36 non-drinkers, 18 moderate drinkers, and 18 heavy drinkers) and 17 matched healthy controls. MetaboAnalyst and PICRUSt2 were utilized to analyze the possible involved metabolic pathways. Multi-omics analysis was achieved by Spearman correlation to reveal the interactions of alcohol consumption with gut microbiome and serum metabolites in patients with CAD. Results: We noted distinct differences between patients with CAD, with varying levels of alcohol consumption and healthy controls in aspects of serum metabolome and the gut microbiome. Moderate alcohol consumption significantly changed the lipidomic profiles, including reductions of sphingolipids and glycerophospholipids in moderate drinkers with CAD when compared with non and heavy drinkers with CAD. Moreover, we also found the reduction of microbial-derived metabolites in moderate drinkers with CAD, such as 2-phenylacetamide and mevalonic acid. To be noted, the gut microbiota of moderate drinkers with CAD tended to resemble that of healthy controls. Compared with non-drinkers, the relative abundance of genus Paraprevotella, Lysinibacillus was significantly elevated in moderate drinkers with CAD, while the genus Bifidobacterium, Megasphaera, and Streptococcus were significantly reduced in moderate drinkers with CAD. Multi-omics analysis revealed that specific metabolites and microbes associated with moderate alcohol consumption were correlated with the severity of CAD. Conclusions: Our study revealed that the impact of moderate alcohol consumption on serum metabolites and gut microbiota in patients with CAD seemed to be separated from that of heavy and non-alcohol consumption. Moderate drinking tended to have more positive effects on metabolic profiles and commensal flora, which may explain its beneficial effects on cardiovascular health. Overall, our study provides a novel insight into the effects of moderate alcohol consumption in patients with CAD.

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Acetate reprograms gut microbiota during alcohol consumption.

Publications

Acetate reprograms gut microbiota during alcohol consumption.

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