DIETARY FIBER ALLEVIATES ALCOHOLIC LIVER INJURY VIA BACTEROIDES ACIDIFACIENS AND SUBSEQUENT AMMONIA DETOXIFICATION

Background and aims: Alcoholic liver disease (ALD) is one of the most prevalent chronic liver diseases and an increasing healthcare burden worldwide. The aim of this study was to investigate the effects of dietary fiber and gut microbiota on ALD and to explore the molecular regulatory mechanisms.
Methods: C57BL/6 mice were subjected to chronic-plus-binge ethanol feeding and supplemented with dietary fiber to determine alcohol-induced liver injury. Microbial community amplicon sequencing analysis and metabolomics were used to analyze the changes in bacterial abundance and metabolites in the gut of mice. The differentially expressed target genes in the liver were identified by proteomic analysis. The gut microbiota-metabolism-target signaling pathway was further validated in in vivo and in vitro models using adeno-associated viruses and small molecule inhibitors.
Results: A high soluble dietary fiber diet reshaped the gut microbiota of mice with ALD and increased the abundance of Bacteroides acidifaciens, which could alleviate alcohol-induced liver injury in mice. Mechanistically, this strain regulates bile acid metabolism via bile salt hydrolase, which in turn activates the FXR-FGF15 pathway in the gut and promotes the expression of ornithine aminotransferase (OAT) in hepatocytes. OAT facilitates the metabolism of ornithine accumulated in the alcoholic liver to glutamate and supplies raw materials for liver detoxification in order to mitigate liver cell damage caused by ammonia accumulation.
Conclusions: Soluble dietary fiber can increase the abundance of Bacteroides acidifaciens in the intestines of ALD mice, thereby protecting hepatocytes from ammonia toxicity and oxidative stress via the FXR-FGF15-OAT axis. Our findings explore the molecular mechanism of alcohol-induced liver injury and propose a novel therapeutic approach for ALD involving dietary fiber and probiotics.
Lay summary: The current study unveils that soluble dietary fiber can alter the composition of the gut microbiota in mice with alcoholic liver disease and play a role in preventing alcohol-induced liver injury. The data demonstrated that soluble dietary fiber increased the abundance of Bacteroides acidifaciens, which alleviated ammonia toxicity and oxidative stress injury in the liver via the "liver-gut axis." These results illustrate the clinical potential of soluble dietary fiber and Bacteroides acidifaciens for treating alcoholic liver disease.