TAS2R10 and obesity due to melanocortin 4 receptor deficiency: This study makes contributions to our current understanding of TAS2Rs in the intestinal tract by elucidating how TAS2R10 and TAS2R43 differentially regulate gut defense against E. coli through antimicrobial peptide secretion and mucus remodeling, respectively, while revealing clinically important modulation by obesity and genetic polymorphisms.