Research finding could lead to new treatments for celiac disease

McMaster UniversityOct 9 2015

A team of researchers has discovered that bacteria found in the gut may contribute to the body's response to gluten, an important finding that could lead to new treatments for celiac disease.

The findings, published today in The American Journal of Pathology, address a lingering question that has preoccupied scientists: why only a small amount - 2 to 5 per cent — of individuals who are genetically susceptible go on to develop the disease.

Recognized as one of the most common chronic conditions in the world, celiac disease affects approximately 300,000 Canadians. It interferes with the ingestion of gluten, a protein found in wheat, rye, and barley, triggering a series of responses that result in damage to the lining of the small intestine critical for the digestion of nutrients.

Many more cases, however, go undiagnosed.

"Importantly, our data argues that the recognized increase in celiac disease prevalence in the general population over the last 50 years could be driven, at least in part, by perturbations in intestinal microbial ecology", explained lead investigator Elena Verdu, an associate professor in the Department of Medicine at the Farncombe Family Digestive Health Research Institute at McMaster University.

"Specific microbiota-based therapies may aid in the prevention or treatment of celiac disease in subjects with moderate genetic risk," she says.

Using germ-free mice that express the human gene which makes them moderately susceptible to inflammatory responses to gluten, researchers compared immune responses and pathology in the gut to two other groups of mice: those conventionally raised with a complex microbiota (SPF) that include potentially pathological organisms (pathobionts) such as E. coli, Staphylococcus and Helicobacter, and mice with ultra-clean microbiota without these opportunists.

Researchers found that the microbiota affects the way mice respond to gluten. In the group without bacteria (germ-free) and the one with pathobionts, gluten responses were enhanced compared to those colonized with ultra-clean microbiota. Moreover, say researchers, if they take the conventional SPF mice and further expand the group of pathobionts with a specific antibiotic that does not affect them but other bacteria, mice develop even more severe responses to gluten.

When researchers supplemented the ultra-clean mice—those protected from gluten—with E. coli, a Proteobacteria that is isolated from the intestine of a celiac patient, a similar reaction occurred.

The next steps will focus on identifying and characterizing the specific mechanisms by which presence of these pathobionts can alter gluten-induced responses in a host. These mechanisms could then be targeted in the future to decrease celiac risk or gluten sensitivity.