Only a small number of individuals who are genetically vulnerable to celiac disease actually acquire this condition, though the reasons why have been unclear. Now, a new study suggests it may be down to how certain gut bacteria respond to gluten.
Celiac disease is an immune disease in which a person is gluten intolerant. Gluten is a protein found in grains including rye, wheat and barley. It is supposed that around 1% of the American population has celiac disease.
When an individual with celiac disease consumes gluten, the immune system responds by harming the small intestine. This may result in abdominal pain, diarrhea, bloating and fatigue, alongside with other symptoms.
Specific gene mutations are known to cause celiac disease. Although, only 2-3% of people who possess such mutations actually develop the condition.
In an effort to conclude why this is, lead investigator Dr. Elena F. Verdu, of the Digestive Health Research Institute at McMaster University in Canada, and colleagues observed at how the immune responses to gluten changed with various populations of gut bacteria in mouse models of gluten intolerance.
Germ-free mice showed signs of celiac disease is response to gluten
The team deployed three groups of mice that represented a gene called DQ8, which is found in humans and makes them genetically at risk to gluten intolerance.
Facts about celiac disease:
- Around 83% of Americans with celiac disease are undiagnosed or misdiagnosed with other conditions
- The only existing treatment for celiac disease is a gluten-free diet
- Around 5-22% of people with celiac disease have a first-degree relative with the condition.
Each group of mice had diverse gut bacteria compositions, or gut microbiomes. One group was germ-free, while another group was clean specific-pathogen-free (SPF); their gut microbiomes were free of Proteobacteria – a group of gram-negative bacteria – and opportunistic pathogens.
The other group was made up of conventional SPF mice, which possessed a wide range of gut bacteria, including Proteobacteria and opportunistic pathogens such as Staphylococcus, Streptococcus andHelicobacter.
The researchers made each group of mice liable to gluten. They concluded that the germ-free mice showed increased levels of intraepithelial lymphocytes (IELs) in the gut; proliferation and activation of IELs is an early indicator of celiac disease. Raised IEL levels were not noticed in the clean SPF mice.
Moreover, the germ-free mice experienced increased death of cells that line the gastrointestinal tract, called enterocytes, next to anatomical alterations of the small, fingerlike projections that line the small intestine, known as the villi.
The researchers also detected the occurrence of antibodies in response to a component of gluten – called gliadin – among the germ-free mice, and these mice also demonstrated T-cell responses specifically to this component.
Amusingly, the team proved that development of gluten-induced pathology was halted in the clean SPF mice compared with the germ-free mice, but this was not the case when the clean SPF mice had enteroadherent Escherichia coli from a patient with celiac disease.