Studies have shown that dysregulation of intestinal microbial structure and co-metabolic imbalance caused by diet and other factors play important role in MASLD and IBD. However, it is unclear how host-microbial interactions differ in the two diseases, and what potential impact they have on accelerating disease progression. Our study aims to find the disease characteristics in MASLD, IBD and their complication from the perspective of host-microbial metabolism. In our study, mouse models of MASLD, IBD, and MASLD-IBD induced by high-fat diet and dextran sulfate sodium. Detecting the pathological changes of colon and liver. Using 16s rRNA to screen out specific micro-flora, and UPLC-MS to monitor the changes of metabolites in feces. The micro-flora-metabolite co-expression network was constructed by Cytoscape software. The result showed that MASLD-IBD mice aggravate intestinal barrier damage, hepatic steatosis and fibrosis, immune inflammation and other pathological changes. In MASLD-IBD mice, the structural change of gut micro-flora is similar to IBD mice, which significantly reduced the abundance of Actinobacteriota, Desulfobacterota while increasing the abundance of Proteobacteria, and the metabolic disorder include nine metabolic pathways, such as tryptophan, bile acids and short-chain fatty acids, is similar to MASLD mice. Their co-expression network indicates that different specific micro-flora are closely related to the metabolic disorder and disease symptoms of MASLD-IBD mice. Analyzing the relationship between intestinal microbial dysregulation and hoetic co-metabolic imbalance is helpful to understand the mechanism of MASLD and IBD comorbidity, which suggesting that combined liver-gut therapy may be a new method for the treatment of MASLD-IBD complication.