Effects Of Alcohol Consumption On The Composition And Potential Physiological Functions Of Human Gut Microbiota

Background: Alcohol use is a major risk factor for global disease burden.Recent studies have shown that changes in gut microbiota are a key factor in the development of alcohol-related diseases.Objective: The aim of this study was to assess differences in gut microbiota composition and function among heavy,moderate,and non/mild drinkers.Methods: Stool samples were obtained from 32 heavy drinkers,35 moderate drinkers,and 24 non/mild drinkers.16 S r RNA gene sequencing was used to detect the composition and function of intestinal flora.Results: Baseline characteristics of the three groups were comparable.With the increase of alcohol consumption,the alpha diversity of microbial community decreased gradually.Beta diversity analysis showed that there were differences in the community composition of intestinal microbiota among the three groups,and the differences were greater between heavy drinking group and non/mild drinking group.The relative abundance of phylum Fusobacteria was significantly increased in the heavy and moderate drinking groups compared to the no/light drinking group.LEf Se analysis showed that there were 18 different genera between heavy and non/mild drinking group,12 different genera between moderate and non/mild drinking group,and 7 different genera between heavy and moderate drinking group.Receiver operating characteristic(ROC)curve analysis suggested that 10 genera(including Fusobacterium,Lachnospira,Phascolarctobacterium,Enterobacter,Eubacterium＿eligens＿group,Romboutsia,Streptococcus,Ruminococcaceae＿UCG-014,Coprococcus＿2 and Eubacterium＿ventriosum＿group)have the potential to distinguish between heavy and non/mild drinkers(area under the ROC curve = 0.9102,95% confidence interval: 0.8260-0.9943).Correlation analysis showed that Fusobacterium and Succinivibrio were positively correlated with alcohol consumption;Enterobacter,Veillonella,Lachnospira,Ruminococcaceae＿UCG＿014,Romboutsia,Streptococcus,Eubacterium＿eligens＿group,Coprococcus＿2,Ruminiclostridium＿6,Cronobacter,Haemophilus,Akkermansia,and Holdemanella were negatively correlated with alcohol consumption.Functional analysis showed that the expression of gut microbial NOD(nucleotide-binding oligomerization domain)-like receptor signaling pathway,glutamate metabolism pathway and nicotinamide adenine dinucleotide(NAD)biosynthesis were increased in the heavy drinking group,while the expression of xylene and toluene degradation pathways was decreased.The correlation analysis between different bacteria and these different pathways showed that Fusobacterium was positively correlated with NOD-like receptor signaling pathway and D-glutamine and D-glutamate metabolism pathway.Some genera significantly reduced in the gut of drinkers were negatively correlated with NOD-like receptor signaling pathway and positively correlated with xylene and toluene degradation pathways.Conclusion: Long-term alcohol consumption induces changes in gut microbiota composition and function.Gut microbiome develops in a dysregulated direction with increasing alcohol consumption,characterized by an increase in potentially pathogenic bacteria(e.g.,Fusobacterium and Succinivibrio)and a decrease in beneficial bacteria such as short chain fatty acids(SCFAs)-producing bacteria.Heavy drinking caused a significant increase in the abundance of inflammation-related NOD-like receptor signaling pathway,glutamate and γ-aminobutyric acid(GABA)neurotransmitter metabolism pathways and NAD biosynthesis pathway related to ethanol metabolism,and a significant decrease in xylene and toluene toxicity degradation pathways.