Research Highlights How Western Diet Contributes to Liver Disease

New research has established a link between Western diets high in fat and sugar and the development of non-alcoholic steatohepatitis, known more widely as non-alcoholic fatty liver disease (NAFLD), the leading cause of chronic liver disease.

The study, conducted by the University of Missouri School of Medicine and published in the journal Nature Communications, identified Western diet-induced microbial and metabolic contributors to liver disease. In the study, researchers found a choline-low, high-fat, and high-sugar diet, representing a typical Western diet, named CL-HFS, successfully induces male mouse NAFLD with some features of the human disease, such as hepatic inflammation, steatosis, and fibrosis.

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For the study, the researchers tested treating the mice with an antibiotic cocktail administered via drinking water. They found that the antibiotic treatment reduced liver inflammation and lipid accumulation, resulting in a reduction in fatty liver disease.

Metataxonomic and metabolomic studies identify Blautia producta and 2-oleoylglycerol as clinically relevant bacterial and metabolic mediators contributing to CL-HFS-induced NAFLD. In vivo studies validate that both Blautia producta and 2-oleoylglycerol promote liver inflammation and hepatic fibrosis in normal diet- or CL-HFS-fed mice, according to the study abstract.

Cellular and molecular studies reveal that the GPR119/TAK1/NF-κB/TGF-β1 signaling pathway mediates 2-oleoylglycerol-induced macrophage priming and subsequent hepatic stellate cell activation, the study abstract said.  

These results suggest that antibiotic-induced changes in the gut microbiota could suppress inflammatory responses and liver fibrosis. These findings advance clinical understanding of NAFLD pathogenesis and provide targets for developing microbiome and metabolite-based therapeutic strategies against NAFLD, the researchers said. 

“Fatty liver disease is a global health epidemic,” said Kevin Staveley-O’Carroll, MD, PhD, one of the lead researchers and a professor in the department of surgery, in a statement. “Not only is it becoming the leading cause of liver cancer and cirrhosis, but many patients I see with other cancers have fatty liver disease and don't even know it. Often, this makes it impossible for them to undergo potentially curative surgery for their other cancers.”