Saturated dietary fat prevented unsaturated fat and alcohol‐mediated alterations in gut microbiota resulting in attenuation of intestinal barrier disruption and liver injury in an animal model of alcoholic liver disease (822.9)

Abstract

Introduction: Gut microbiota play an important role in the pathogenesis of ALD. Dietary fat and alcohol both affect microbiota composition and abundance. The aim of the study was to evaluate the effects of different types of dietary fat on alcohol‐mediated changes in gut microbiota and consequent intestinal and liver injury. Materials and Methods: C57BL/6 mice were fed either saturated (medium chain triglycerides enriched [MCT]) or unsaturated (corn oil enriched) fat diet containing 5% ethanol for 8 weeks. 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 pyrosequencing on the 454 FLX Titanium platform. Intestinal barrier integrity; liver injury and steatosis were evaluated. Results: Dietary unsaturated fat and ethanol caused a decline in the abundance of both Bacteriodetes and Firmicutes phyla, with a proportional increase in the gram negative Proteobacteria and gram positive Actinobacteria phyla. The observed microbiota changes were associated with the alterations in the intestinal tight junctions; liver inflammation and injury. Notably, unsaturated fat and ethanol induced pathogenic alterations in the gut microbiome, intestinal barrier integrity, and the livers were prevented in animals receiving saturated fat diet and ethanol. Conclusion: ALD relevant pathogenic alterations in the gut microbiome induced by chronic ethanol are markedly influenced by dietary lipids. Dietary lipids can potentially provide therapeutic options in the management of ALD.Grant Funding Source: Supported by NIH, DOD and Veterans Administration