Microbiome dysbiosis is strongly associated with alcoholic liver disease(ALD).Recent studies on comprehensive analyses of microbiome compositional and functional changes have begun to uncover the mechanistic relation between microbiome and the pathogenesis of ALD.Importantly,targeting the microbiome has become a potential strategy for the prevention and treatment of ALD.In this review,we summarize the clinical evidence of microbiome dysbiosis in ALD patients,and experimental advances in microbiome and metabolomic functional changes in animals with different species and genetic back-grounds in ALD.We also summarize the studies in humanized intestinal microbiome and fecal micro-biota transplantation in mice.We introduce new developments in the studies on the role of the circulating bacterial microbiome,oral bacterial microbiome and fungal microbiome in the development of ALD.We highlight the potential mechanisms by which microbiome dysbiosis contributes to ALD,including short chain fatty acid changes,bile acid metabolism,intestinal barrier function,release of bacterial and fungal products,and inflammation.In addition,we summarize the recent developments targeting the microbiome in prevention and treatment of ALD,including dietary nutrient interference,herbal medicine,antibiotics,anti-fungal agents,probiotics,engineered bacterial therapy,fecal trans-plantation and oral hygiene.Although recent preclinical studies have advanced our understanding of the microbiome and ALD,clinical studies,especially prospective studies with large samples,are needed to better understand the cause-effect of microbiome dysbiosis in ALD.Identifying new precision-based strategies targeting the microbiome are expected to be developed as more effective therapies in ALD.

Alcoholic liver disease(ALD)comprises a spectrum of liver pathology,including steatosis,steatohepatitis,and cirrhosis.Previous work from our group and others suggests that dietary fat,both the amount and composition,plays a pivotal role in ALD development and progression;however,the impact of specific dietary fatty acids on ALD pathogenesis is not fully elucidated.Preclinical rodent models of ALD revealed the deleterious effects of omega-6 polyunsaturated fatty acids(n-6 PUFAs),specifically linoleic acid(LA),and this may be partially attributed to the increased levels of pro-inflammatory oxidized LA metabolites.There is limited understanding regarding the role of omega-3 polyunsaturated fatty acids(n-3 PUFAs,such as alpha-linolenic acid,eicosapentaenoic acid,and docosahexaenoic acid),and bioactive n-3 PUFA-derived lipid molecules in ALD.Given that majority of n-6 and n-3 PUFAs-derived metabolites are potent endogenous signaling molecules,knowledge regarding the changes in these lipid mediators may shed new light on the mechanisms contributing to ALD pathogenesis and reveal novel therapeutic targets and biomarkers of this disease.The current review summarizes relevant scientific literature regarding the role of dietary fat,distinct fatty acids,and bioactive fatty acid metabolites in ALD,and highlights recent advances in the field.