A 10-year study of urban slum children in Bangladesh has resulted in a groundbreaking discovery that helps explain how our bodies control disease susceptibility to a life-threatening diarrheal infection.
“Leptin is the hormone produced by our fat cells that tells us to stop eating,” says William A. Petri, Jr., MD, PhD, chair of the Division of Infectious Diseases and International Health in the UVA School of Medicine. “The lack of leptin causes obesity, because the brain never receives a signal to stop eating. But now we know that this same hormone that keeps us from becoming obese also protects us from infection.”
The University of Virginia-led study, now available online and appearing in the March 2011 issue of The Journal of Clinical Investigation, reports important findings that the fat hormone, leptin, helps children remain healthy by preventing the infection amebiasis. Caused by the parasite Entamoeba histolytica, amebiasis is a serious disease that can affect anyone but is more common in people who live in crowded areas with poor sanitary conditions.
The World Health Organization (WHO) has estimated that E. histolytica infection results in 34 to 50 million cases worldwide each year leading to as many as 100,000 deaths annually. In Dhaka, where diarrheal diseases are a leading cause of childhood death, the annual incidence of E. histolytica infection among preschool children is 40 percent.
Petri and a team of UVA investigators have spent the last 10 years observing 300 children in Dhaka, Bangladesh through home visits three times a week. In addition to providing free medical care to the children, investigators discovered a remarkable link between a specific genotype and resistance to infection.
“Through a series of genetic studies, we found that children who had a common genetic variation, or polymorphism, in the receptor for leptin were protected from ever becoming infected with the enteric pathogen E. histolytica,” Petri says.
Researchers are now examining the role of leptin in serious infections common in the United States, such as infections from Clostridium difficile. A bacterium that can cause diarrhea and life-threatening illness, C. difficile in recent years has become much more frequent, severe and difficult to treat. Illness from C. difficile most commonly affects older adults in hospitals or in long-term care facilities. Petri’s research team also is testing the role of leptin as a natural therapy for infections.
The study, which involved investigators from Johns Hopkins University, was supported by grants from the National Institutes of Health (NIH).
Key contributors to the discovery include Priya Duggal from Johns Hopkins who led the human genetics studies, co-first author Xiaoti Guo, now at the NIH who studied the mechanism of action of leptin, Rashidul Haque who leads the study and care of children in the urban slum cohort in Bangladesh, and Kristine Peterson at the University of Virginia who designed the clinical studies.