Enteric and Diarrheal Disease

Scott Jordan Kerns of Harvard Medical School in the U.S. will develop a cell-based model of environmental enteric dysfunction, which causes substantial morbidity and mortality in developing countries. As a living model of the human intestine, he will use a gut-on-a-chip device composed of two microfluidic channels enclosing gut cells growing on a flexible membrane, which is coated with extracellular matrix proteins and other cell types.

Honorine Ward of Tufts Medical Center with Mary Estes at Baylor College of Medicine in the U.S. and Gagandeep Kang at Christian Medical College in India will develop a three dimensional cell culture model (enteroid) of the human intestine to study environmental enteric dysfunction (EED), which is associated with substantial morbidity in young children in the developing world. They will grow enteroids from isolated intestinal crypts derived from unused surgical samples from children with and without EED in India.

Seth Walk of Montana State University in the U.S. will develop an in vitro model system composed of three dimensional intestinal tissue (organoids) and microfluidics to quantitate the effect of diarrhea-causing bacteria on intestinal function. They have already grown stable multicellular intestinal organoids displaying typical intestinal structures and function from human intestinal stem cells. Now, they will incorporate fluidics to represent flow inside the gastrointestinal tract to more closely mimic gut physiology in vivo.

Michel Bagnat of Duke University in the U.S. will study new genetic zebrafish models of acute secretory diarrhea and environmental enteric dysfunction, which are normally caused by infectious pathogens in humans, to study disease pathogenesis and facilitate development of new therapies. The zebrafish intestine has a similar physiology to the human organ, making zebrafish a valuable genetic model for studying human intestinal diseases. They have already isolated zebrafish mutants displaying characteristics of the relevant human diseases.

Carson Meredith from Georgia Tech in the U.S. will determine whether pollen can measure gut function by assessing mucus qualities, which vary along the gastrointestinal tract particularly in children with enteric diseases. Gastrointestinal mucus prevents pathogens entering the body and promotes the absorption of nutrients and medicines. Therefore, its physical properties are relevant for gut health and the development of effective treatments. Pollen particles vary widely in size and shape, and can survive the harsh environment of the gastrointestinal tract.

Marcela Pasetti of the University of Maryland in the U.S. will generate an in vitro model of the gut using intestinal stem cells and immune cells to better mimic the damaged and inflamed guts of young children in developing countries for testing new treatments. Current so-called human enteroid models lack additional relevant cell types found in the intestine, particularly immune cells, which are known to play an important role in gut health and function.

Cirle Warren from the University of Virginia in the U.S. will develop a mouse model with an intestinal tract that is primed to mimic the human intestine in order to better study enteric infections and identify effective treatments. Several environmental enteropathies cannot be studied in the mouse because they do not simulate the human physiological response. To address this, they will test different conditions for transplanting feces from healthy children into pregnant mice to transfer human gut microbes and promote the development of a 'humanized' gut in the unborn mice.

Ralph Tripp from the University of Georgia in the U.S. and Carl Kirkwood of Murdoch Children's Research Institute in Australia will engineer mammalian cell lines for the development of vaccines and therapies against human noravirus and related enteric viruses. Noravirus is highly contagious and causes acute gastroenteritis, which can be serious in young children and the elderly. However, studying the virus and developing much needed new therapies has been difficult because mammalian cells are unable to support replication of the virus and grow in culture.

Linda Saif from Ohio State University in the U.S. will develop a pig model to recapitulate the vicious cycle of malnutrition and repeated enteric infections seen in young children in developing countries in order to study the underlying biology and identify effective treatments. Childhood malnutrition is rife in impoverished regions, and causes substantial mortality and disabilities. It impairs gut function and immunity, and leads to increased enteric infection rates.

Nur Alam of the International Centre for Diarrhoeal Disease Research, Bangladesh will test whether adding L-isoleucine and Vitamin D to food served to hospitalized children will induce secretion of antimicrobial peptides that can aid recovery from acute diarrhea and pneumonia.