Compared with WT mice, we observed for the first time that ASPP2-deficient caused (i) moderate steatosis in early-stage of NAFLD and severe liver damage in later-stage of NAFLD, respectively; (ii) significantly alterations in hepatic long chain fatty acid (mainly omega-3 PUFAs) metabolism and gut microbiota composition in the early-stage of NAFLD; (iii) a significant correlation between hepatic FA 20:5 and bifidobacteria family and genus. The gene discussed is TP53BP2; the disease is steatosis.