Western diet linked to hepatic inflammation.

What is it about?

Patients who have liver cirrhosis and liver cancer also have reduced farnesoid X receptor (FXR). Similarly, mice that lack of FXR develop spontaneous liver cancer and have increased susceptibility to colitis, cholestasis, and colon cancer. These findings clearly indicate the interactive effect of hepatic and gut FXR in contributing to liver carcinogenesis. Moreover, elevated BAs found in FXR KO mice contribute to liver carcinogenesis because cholestyramine can prevent it. Due to the significance of BAs in inflammation and carcinogenesis, the current study uncovers whether the specific BAs that contribute or protect hepatic inflammation in response to a western diet (WD) intake in FXR KO mice. We found that Male WD-fed FXR KO mice had the most severe steatohepatitis. FXR KO also had reduced Firmicutes and increased Proteobacteria, which could be reversed by Abx. Additionally, Abx eliminated hepatic neutrophils and lymphocytes in CD-fed, but not WD-fed, FXR KO mice. Proteobacteria and Bacteroides persisted in WD-fed FXR KO mice even after Abx treatment. Only PolyB could reduce hepatic lymphocytes in WD-fed FXR KO mice. The reduced hepatic inflammation by antibiotics was accompanied by decreased free and conjugated secondary BAs as well as changes in gut microbiota. Our data revealed that Lactococcus, Lactobacillus, and Coprococcus protect the liver from inflammation. Thus, probiotics and FXR agonists should be effective in prevention and treatment of hepatic inflammation and progression into advanced liver diseases such as cancer .

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Why is it important?

We identified the specific bile acids and bacteria that are associated with the development of hepatic inflammation under the influence of diet, microbiota, and FXR inactivation. Lack of FXR and Western diet intake increases free and secondary bile acids. Antibiotic treatment also changes bile acid profile and the severity of hepatic inflammation. Lack of FXR reduces the abundance of Firmicutes but increases the abundance of Proteobacteria. After broad-spectrum antibiotic treatment, Proteobacteria and Bacteroidetes remain in Western diet-FXR knockout mice. Proteobacteria generate lipopolysaccharide, which may contribute to the development of non-alcoholic steatohepatitis. Thus, probiotics potentially can be used to prevent and treat steatohepatitis.

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