Changes in gut microbiota composition in Tas1r3-deficient mice

Excessive intake of a western diet (WD), characterized by high fat and sugary drinks, is hypothesized to contribute to the development of inflammatory bowel disease (IBD). Despite the identified clinical association, the molecular mechanisms through which dietary changes lead to IBD development remain unknown. Here, we generated a murine model of severe intestinal inflammation triggered by long-term WD consumption, which exhibited markedly elevated taste receptor TAS1R3 expression in inflamed bowel tissues. Thus, we hypothesized that nutrient-induced TAS1R3 modulation is central to regulating intestinal inflammation. We tested our hypothesis by analyzing changes in gene expression profiles, inflammatory cell infiltration in the intestinal tissues, and the gut microbiome of WD-fed Tas1r3-deficient mice. Interestingly, we confirmed that Tas1r3-deficient mice are protected from WD-induced intestinal inflammation. Notably, the upregulation of tight junction proteins and antimicrobial peptides in Tas1r3-/- mice prompted us to investigate how TAS1R3 deficiency affects the gut microbial community structure. To this end, we performed high-throughput gene sequencing analysis of 16S rRNA in fecal bacterial DNA isolated from Tas1r3-/- mice and littermate WT controls fed normal diet (ND) or western diet (WD).