University of Arizona Obtains $1.9 Million U.S. Government Grant To Study Key Protein’s Role in Bowel Disease

University of Arizona Obtains $1.9 Million U.S. Government Grant To Study Key Protein’s Role in Bowel Disease

University of Arizona scientists have received a $1.9 million U.S. government grant to study how a protein helps maintain a healthy mix of gut bacteria, and how interfering with the protein can lead to bowel disease and colon cancer.

The Steele Children’s Research Center study will focus on the NHE8 protein, which helps facilitate sodium absorption in the gut and plays other roles there. Among other things, sodium absorption affects the gut’s ability to convert nutrients the body will use for energy and other functions.

Dr. Fayez K. Ghishan and his colleagues at the center were the first researchers to characterize NHE8’s function in the intestine.

A division of the National Institutes of Health, the National Institute of Diabetes and Digestive and Kidney Diseases, is supplying the five-year grant. Ghishan and Dr. Hua Xu will lead the study.

Ghishan said in a press release that until a recent study his team did, the researchers thought NHE8 was involved only in sodium absorption. They discovered that deleting NHE8’s function in the gut leads to “goblet cell dysfunction, changes in the microbiota, and the hyper-proliferation of epithelial cells.” And those changes lead to colon cancer.

Goblet cells secrete mucus, a protective barrier lining the gut. Microbiota is the term scientists use to refer to the mix of bacteria in the gut. And epithelial cells line hollow organs and glands.

“This is a major grant with the potential to shed light on the mechanisms behind gastrointestinal diseases and colon cancer – diseases that not only affect quality of life for many Americans, but also can lead to death,” said Robert C. Robbins, the president of the University of Arizona. “The foundational work for this research happened at the UA [the University of Arizona], and so it’s fitting that the NIH [National Institutes of Health] is providing the investment needed so our researchers can take it even farther.”

One of the things the grant will allow the researchers to do is study NHE8’s role in goblet cell function. Those specialized intestinal epithelium cells secrete the mucus that protects the gut.

“Mucus is very important because it separates bacteria in the GI [gastrointestinal] tract from the lining of the GI tract,” Ghishan said. “When NHE8 was removed, goblet cells secreted less mucin.” This reduced the “protective barrier of mucus, enabling the bacteria in the lumen [or space inside the intestines] to get closer to the intestinal lining.” The result was inflammation that can cause diseases such as ulcerative colitis.

The Arizona team will also investigate the link between NHE8 and the gut microbiome, and why deleting NHE8 causes an imbalance in the microbiome, which scientists call dysbiosis.

The research should make important contributions to scientists’ understanding of diseases such as irritable bowel syndrome and colon cancer.

“Normal tissue versus tissue with colon cancer” shows that “NHE8 is not present in colon cancer tissue samples,” Ghishan said. “Clearly when you knock out NHE8, you develop polyps and colon cancer.”

“We believe this study will shed new light on colonic tumor development and potentially provide new ideas for early detection and provide better treatment options,” Xu said.

“In addition to possibly discovering insights into a mechanism of colon cancer development, our findings about how NHE8 impacts goblet cell function and microbiota homeostasis [stability] may lead to novel treatments for IBD and other inflammation problems of the gut,” Ghishan concluded.