Alcohol-dependent downregulation of apolipoprotein H exacerbates fatty liver and gut microbiota dysbiosis in mice

Abstract

Background Alcohol-related liver disease (ALD) is a major chronic liver ailment caused by alcohol overconsumption and abuse. Apolipoprotein H (APOH) participates in lipid metabolism and might have a potential regulatory role in ALD. Therefore, this study aimed to explore the effects of ApoH on alcohol-induced liver injury and gut microbiota dysbiosis. Methods ApoH−/− mice were generated and the synergic alcoholic steatohepatitis mouse model was constructed, which were used to assess liver function and pathological changes. Results ApoH−/− mice clearly exhibited spontaneous steatohepatitis. Severe hepatic steatosis was observed in alcohol-fed WT and ApoH−/− mice, in which ApoH expression was reduced post alcohol consumption. Moreover, RNA-seq and KEGG pathway analyses indicated that differential expression genes enriched in lipid metabolism and oxidation–reduction process between in alcohol-fed ApoH−/− mice and pair-fed control mice. Finally, gut microbiota diversity and composition were assessed by 16S rRNA Illumina next-generation sequencing. Alpha diversity of enterobacteria was lower in ApoH−/− mice with ethanol feeding than in ethanol-fed WT mice and all control-fed mice (P < 0.05). Moreover, KEGG enrichment analysis, using PICRUSt software, revealed that metabolic functions were activated in the gut microorganisms of ApoH−/− mice with ethanol feeding (P < 0.05). Conclusions Alcohol-downregulated ApoH expression, leading to the progress of fatty liver disease and gut microbiota dysbiosis.

Bifidobacterium lactis TY-S01 protects against alcoholic liver injury in mice by regulating intestinal barrier function and gut microbiota

“…Therefore, TY-S01 was able to maintain the diversity of gut microbiota, which was not affected by alcohol in our studies. In addition, excessive alcohol intake can also affect the abundance of the bacterial community and lead to bacterial imbalances [ 44 ]. We further investigated the abundance of specific species in the gut with or without TY-S01 treatment.…”

Apolipoprotein H induces sex-specific steatohepatitis and gut dysbiosis during chronic hepatitis B infection

“…The detail protocol for the generation of the ApoH -/- mouse model was described in our previous publication. 37 …”

Apolipoprotein H-based prognostic risk correlates with liver lipid metabolism disorder in patients with HBV-related hepatocellular carcinoma

“…The previous study primarily focused on the correlations between APOH and HBV infection and elucidated that HBV and its large surface antigen directly upregulates APOH expression, which inhibits HBsAg secretion and induces hepatocyte ER stress [ 7 , 8 ]. Further studies clarified that ApoH gene knockout mouse appears spontaneous steatohepatitis and APOH deficiency disrupted hepatic lipid metabolism and gut microbiota homeostasis [ 9 , 10 ]. Based on these complied results, APOH might be a hinge point in fatty liver disease incidence and progression during chronic HBV infection and we focus on this direction in the present study.…”