Intestinal Microbiome in NHE2/3 Null Mouse Models

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Sodium/proton exchangers (SLC9s, NHEs) play an integral role in sodium absorption in the intestine. Studies using knockout mice showed that loss of NHE3, but not NHE2, results in diarrhea. The intestinal contentin NHE3−/− mice is significantly more alkaline than in WT littermates. Alkalinizationof the normally acidic microclimate immediately adjacent tothe brush-border surface layer may aid bacterialadhesion and facilitate microbial-epithelial interactionsand translocation. This study sought to determine the effect of altered intestinal ion transport in NHE2−/− and NHE3−/− mice on the luminal and mucosa-associated microbiota. Data using 16S ribosomal DNA bacterial primers in quantitative real time PCR (qRT-PCR) revealed increases in total bacteria in the terminal ileum and distal colon of NHE3−/− mice and no change in the total bacteria of NHE2−/− mice. Interestingly decreases in beta-Proteobacteria were observed in NHE3−/− terminal ileum, cecum, proximal colon and distal colon and in NHE2−/− cecum. In NHE3−/− mice, decreases in alpha-Proteobacteria were observed in proximal and distal colon, while in NHE2−/− mice alpha-Proteobacteria was found to increase in the distal colon. Finally, gamma-Proteobacteria was found to increase only in NHE2−/− proximal colon. These data suggest that differences in intestinal ion transport can result in changes in bacterial families which may increase the susceptibility of the host to intestinal inflammation and dysfunction. Supported by NIH DK079979 to RTW and DK050594 to GES.