Researcher at Medical College of Wisconsin and Children’s Hospital of Wisconsin to Study Non-Alcohol Fatty Liver Disease

Nita H. Salzman, M.D., Ph.D., a pediatric gastroenterology researcher at the Medical College of Wisconsin (MCW) and Children’s Hospital of Wisconsin, received a five-year, $7 million grant from the National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases. The award will fund an investigation into the link between intestinal bacteria and non-alcoholic fatty liver disease (NAFLD).

Dr. Salzman, associate professor of pediatrics in gastroenterology at MCW and a researcher at Children’s Hospital of Wisconsin Research Institute, and Ingrid B. Borecki, Ph.D., associate professor of biostatistics and genetics at Washington University School of Medicine in St. Louis, are the principal investigators of the grant.

Non-alcoholic fatty liver disease occurs when excess fat has built up in liver cells due to causes other than alcohol. Preliminary estimates indicate this disease affects up to a third of Americans. The incidence of NAFLD in children is increasing significantly in the U.S. in parallel with the increasing prevalence of obesity and type 2 diabetes, and is rapidly becoming a major reason for liver failure and transplantation. Non-alcoholic fatty liver disease can progress into non-alcoholic steatohepatitis, in which the liver is inflamed and may ultimately develop cirrhosis. Non-alcoholic steatohepatitis occurs in approximately three percent of the general population, yet may be found in more than 25 percent of obese persons.

In this project, researchers are interested in recent evidence demonstrating a link between obesity, non-alcoholic fatty liver disease and the bacterial makeup of the intestines. The gastrointestinal tract is colonized by a vast, complex and delicately balanced ecosystem comprised of bacteria, fungi and viruses, known as the intestinal microbiome. The intestinal microbiome plays an important role in human health by preventing infection, contributing to normal immune function and influencing metabolism. Disruption of this ecosystem has been associated with several diseases including inflammatory bowel disease and obesity, and may lead to abnormal immune and metabolic responses that are hypothesized to be involved in the development of non-alcoholic fatty liver disease.

The goal of this study is to investigate the composition of the intestinal microbiome in obese pediatric patients with and without non-alcoholic fatty liver disease, to determine whether there are differences in their intestinal bacteria that could relate to the development of fatty liver and liver inflammation in children. Understanding how changes in the microboime affect the progression of non-alcoholic fatty liver disease may lead to new methods of predicting NAFLD and novel interventions using prebiotics, probiotics or antibiotics to manipulate the microbiome to prevent or treat the disease.

This project is a nationwide collaboration involving Dr. Salzman, Dr. Borecki and other researchers specializing in hepatology: Aynur Unalp-Arida, M.D., Ph.D., associate scientist in epidemiology at Johns Hopkins Bloomberg School of Public Health in Baltimore, Jeffrey Schwimmer, M.D., associate professor of clinical pediatrics at the University of California at San Diego School of Medicine.