Even though the causative relationship between NHE3 deficiency, dysbiosis, and IBD has not been completely understood to date, we have provided additional evidence that changes in the ionic milieu (Na+ and pH) as a result of intestine-specific deletion of NHE3 provides a competitive advantage for certain microbiota (e.g., Bacteriodetes and Proteobacteria) and a disadvantage for others (e.g., Firmicutes). This may predispose and/or promote pathogenesis of intestinal diseases such as IBD. Here, SLC9A3 is linked to inflammatory bowel disease.