TRMT6 mitigates susceptibility and progression of DSS-induced colitis multifacetedly via translational regulation [16S rRNA-seq]

The intestinal epithelium, a self-renewing single-cell layer, acts as a physical barrier isolating gut microbiota from deeper tissues. In human IBD and experimental IBD mouse models, this barrier is compromised, causing microbial infiltration and inflammation. However, the pathogenesis of IBD remains to be fully understood. Our research shows that the absence of TRMT6 in the mouse gut impairs the intestinal mucosal barrier, increasing susceptibility to DSS-induced colitis. Mechanically, loss of TRMT6 in intestinal epithelial cells disrupts m¹A modification-mediated translational control and impairs MYC protein synthesis–a deficiency that inhibits epithelial cell proliferation and differentiation. Further multi-omics analyses suggest that TRMT6 deficiency may be associated with perturbations in intestinal lipid metabolism, nutrient absorption, metabolite homeostasis, and gut microbiota composition–changes that could collectively contribute to the acceleration of colitis progression. In summary, TRMT6 is crucial for maintaining small intestinal mucosal barrier function, offering insights into how its deficiency may drive gastrointestinal inflammation in IBD. Given the critical role of TRMT6 in maintaining intestinal homeostasis, our findings highlight its potential as a therapeutic target for IBD treatment. Overall design: 16s rRNA gene sequencing of stool samples from WT (n=3) and Trmt6-/- (n=3) DSS-induced colitis mice to investigate the changes in gut microbiota (GM) composition.