High-Fat Proteins Drive Dynamic Changes in Gut Microbiota, Hepatic Metabolome, and Endotoxemia-TLR-4-NFκB-Mediated Inflammation in Mice.

The responses of gut microbiota to dietary proteins have been studied previously. However, the effects of dietary proteins supplemented with a high-fat diet (HFD) on the metabolite biomarkers associated with non-alcoholic fatty liver disease (NAFLD) are not well understood. To understand the underlying mechanisms, C57BL/6J mice were fed with either a low-fat diet with casein (LFC) or an HFD with casein (HFC), fish (HFF), or mutton proteins (HFM), and their cecal microbiota and liver metabolites were analyzed. At the phylum level, the HFD group had a relatively higher abundance of Firmicutes compared to the LFC-diet group. At the genus level, the HFF-diet group had the highest abundance of Lactobacillus and Akkermansia compared to the HFC- and HFM-diet groups. Furthermore, mice fed with the HFF diet had significantly reduced levels of hepatic metabolites involved in oxidative stress and bile acid metabolism. Thus, meat proteins in HFD interact in the host to create distinct responses in the gut microbiota and its metabolites.