Akkermansia muciniphila Ameliorates Alcoholic Liver Disease in Experimental Mice by Regulating Serum Metabolism and Improving Gut Dysbiosis

Abstract

Alcoholic liver disease (ALD) represents a significant global health concern, yet the available treatment options remain limited. Numerous studies have shown that gut microbiota is a critical target for the treatment of ALD. Additionally, there is increasing evidence that host metabolism also plays a crucial role in the development of ALD. Akkermansia muciniphila has been demonstrated to ameliorate experimental ALD through its modulatory effects on the intestinal vascular barrier, enhancement of mucus layer thickness, and promotion of intestinal tight junction proteins. Nevertheless, there is a dearth of studies investigating the impact of A. muciniphila on host metabolism and gut microbiota. Here, C57BL/6 mice were utilized to establish a modified NIAAA model in order to investigate the impact of the oral administration of A. muciniphila during the development of ALD. Furthermore, we employed targeted metabolomics to analyze the serum metabolomic profiles of the mice and 2bRAD-M sequencing to comprehensively examine the underlying mechanisms of the efficacy of A. muciniphila on ALD. Our results illustrated that the oral administration of A. muciniphila alleviated alcohol-induced liver injury in conjunction with encouraged serum levels of ornithine and diminished the elevation of oxalic acid levels induced by alcohol intake. In addition, A. muciniphila also inhibited the proliferation of harmful bacteria, such as Escherichia coli and Helicobacter hepaticus, induced by alcohol consumption while promoting the growth of butyrate-producing and commensal bacteria, including Paramuribaculum intestinale and Bacteroides ovatus. In conclusion, this study suggests that A. muciniphila restores ALD by regulating the gut microbiota, and this corrective effect is associated with alterations in the serum metabolism. Our research supplies a theoretical basis for developing A. muciniphila as an innovative generation of probiotic for preventing and managing ALD.