The UA Steele Children’s Research Center study seeks to decipher how the sodium-hydrogen transporter NHE3 contributes to the health of the gastrointestinal tract.
Individuals have nine sodium-hydrogen exchangers, or “transporters,” known as NHE (Na-H-Exchanger). NHEs are proteins responsible for transporting sodium across the GI tract for absorption. NHE3 is the predominant sodium-hydrogen transporter responsible for the majority of sodium transport across the GI tract.
“When the intestines become inflamed, NHE3 becomes inhibited, so it can’t move sodium through the GI tract, causing diarrhea and other ailments common in those suffering from Inflammatory Bowel Disease and similar autoimmune disorders,” said Ghishan.
Past work from Ghishan and Kiela’s lab focused on changes and regulation of NHE3 during postnatal development. Their research revealed that in addition to transporting salt to the GI tract for absorption NHE3 is involved in preserving the integrity of the epithelial lining – the cellular structure that creates the intestinal wall, which separates the gut contents from the bloodstream.
They showed that when NHE3 is inhibited, or “knocked down” by inflammation, the intestinal wall is breached, the gut becomes leaky and bacteria escape from the intestines into the bloodstream. Consequently, deadly sepsis may develop. Moreover, NHE3 plays a critical role in shaping the intestinal microbiota (the microorganisms that live in the digestive tract). The latter aspect of the new study is particularly intriguing as mice lacking the NHE3 gene have altered microbial gut ecology in ways resembling that observed in IBD patients. “Changes in the composition of intestinal microbiota, which is comprised of 10-times more cells than we have in our entire body, are of profound importance not only in IBD patients, but in the entire body’s metabolism,” said Kiela. Said Ghishan: “Therefore, linking dysfunction of this one intestinal transporter to the intestinal microbial community potentially has much clinical importance.”
Steele Children’s Research Center