How Sugar and Soft Drinks Are Related to Inflammatory Bowel Disease?

Abstract

IBD. NHE3 knockout mice, which display congenital mild diarrhea and reduced body weight develop spontaneous colitis when housed in a conventional facility, and lethal colitis when exposed to low concentrations of dextran sulfate sodium. However, housing these mice in an ultraclean facility improved colitis symptoms emphasizing the importance of the gut microbiome in the development of colitis, as well as an immunomodulatory effect of NHE3 downregulation in IBD. Along these lines, we would like to point to our recent identification of germline mutations in NHE3 and in a regulator of NHE3, guanylate cyclase C in patients with congenital sodium diarrhea. Congenital sodium diarrhea refers to an intractable diarrhea of intrauterine onset with high fecal sodium loss. Recessive NHE3 mutations resulted in absent or nonfunctional protein in a subset of patients, and NHE3 was downregulated in another subset of congenital sodium diarrhea patients harboring constitutively activating and hyper-stimulating mutations in guanylate cyclase C. Interestingly, several patients with germline guanylate cyclase C and NHE3 mutations developed IBD, with varying ages of onset implicating reduced NHE3 activity as a predisposition for IBD. Taken together, NHE3 might be considered to play a role in the composition of the gut microbiota, and its deficiency may thus contribute to dysbiosis observed in patients with IBD.