Tributyrin supplementation attenuates alcohol induced dysbiosis and liver injury

Abstract

Alcohol‐induced enteric dysbiosis plays an essential role in the pathogenesis of alcoholic liver disease (ALD). Detailed characterization of the alterations in the gut microbiome is needed for understanding their pathogenic role in ALD. Mice were fed liquid Lieber‐DeCarli diet without or with alcohol (5% v/v) for 7 weeks. A subset of mice were administered tributyrin (orally gavaged). Tb is a triglyceride that is rapidly absorbed and metabolized to butyrate by pancreatic lipases. Moreover, it has favorable pharmacokinetics compared with butyrate with low toxicity. Effect of tributyrin on alcohol‐induced intestinal dysbiosis and hepatic injury were evaluated. Metagenomic analysis of the gut microbiome was performed by analyzing the fecal DNA by amplification of the V3–V5 regions of the 16S rRNA gene and large‐scale parallel sequencing on the Illumina MiSeq platform. 7 weeks of chronic alcohol feeding caused a decrease in the diversity of the intestinal microbiome which was reversed by tributyrin administration. Notably, the alcohol‐induced pathogenic changes in the microbiome and the liver were prevented by tributyrin administration. Commensurate with the qualitative and quantitative alterations in the microbiome by butyrate, alcohol‐induced increase in plasma endotoxin and elevation of liver enzymes were significantly reversed by tributyrin. Hence, the increase in the diversity of the bacterial communities of the gut may serve as significant therapeutic target for the prevention/treatment of chronic alcohol intake induced intestinal barrier dysfunction and liver disease.