Only a small number of people who are more likely to have celiac disease actually develop the condition, even though the reasons for this have been not definite.
According to a new study, it may be down to how certain gut bacteria respond to gluten.
A person can have Celiac disease, if is intolerant to gluten. Gluten is a protein found in grains including rye, wheat and barley. Approximately 1% of the Americans have celiac disease.
If one person with celiac disease consumes gluten, the immune system responds by bringing about damage to the small intestine. This may be the cause of abdominal pain, diarrhea, bloating and fatigue, among other symptoms.
Certain gene mutations are known to cause celiac disease. But, only 2-3% of genetically susceptible individuals develop the disease.
Using a humanized mouse model of gluten sensitivity, lead investigator Dr. Elena F. Verdu, of the Digestive Health Research Institute at McMaster University in Canada, and colleagues looked at how the immune reacts to gluten varied with various populations of gut bacteria.
This study is published in The American Journal of Pathology.
Germ-free mice showed signs of celiac disease is response to gluten
Three groups of mice were assessed. These groups expressed a gene called DQ8, which is found in humans. This makes them genetically susceptible to gluten intolerance.
Fast facts about celiac disease
• Around 83% of the American people with celiac disease are undiagnosed or misdiagnosed with other conditions.
• Gluten-free diet is the only treatment for celiac disease.
• Around 5-22% of people with celiac disease have a first-degree relative with the condition.
Each group of mice had different gut bacteria compositions, also known as gut microbiomes. One group was germfree, while another group was clean specific-pathogen-free (SPF). Their gut microbiomes were free of Proteobacteria.
The third group was made up of conventional SPF mice. This group had a wide range of gut bacteria, in which Proteobacteria and opportunistic pathogens such as Staphylococcus, Streptococcus and Helicobacter were included.
Each group of mice was exposed to gluten. The researchers discovered that the germfree mice showed enlarged levels of intraepithelial lymphocytes (IELs) in the gut.
Early symptoms are proliferation and activation of IELs. But, enlarged IEL levels were not seen in the clean SPF mice.
Additionally, the germfree mice experienced expanded death of cells that line the gastrointestinal tract that is called enterocytes, alongside anatomical alterations of the small, fingerlike projections that line the small intestine, known as the villi.
Also the development of antibodies was identified. It was in response to a component of gluten – called gliadin – among the germfree mice, and these mice also showed T-cell responses specific to this component.
The team also discovered that the development of gluten-induced pathology was stopped in the clean SPF mice, contrasted with the germfree mice, however, this was not the case when the clean SPF mice received enteroadherent Escherichia coli from a patient with celiac disease.
Increasing proteobacteria worsened gluten-induced pathology
According to the researchers, conventional SPF mice showed greater gluten-induced pathology than clean SPF mice, so the team intended to investigate if the presence of Proteobacteria, such as Escherichia and Helicobacter, plays an important role.
Dr. Verdu said: “These studies demonstrate that perturbation of early microbial colonization in life and induction of dysbiosis (microbial imbalance inside the body), characterized by increased Proteobacteria, enhances the severity of gluten-induced responses in mice genetically predisposed to gluten sensitivity.” She also added:
“Importantly, our data argue 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. Specific microbiota-based therapies may aid in the prevention or treatment of celiac disease in subjects with moderate genetic risk.”
According to Dr. Robin G. Lorenz, of the University of Alabama at Birmingham, these findings indicate the presence of Proteobacteria which can play an important role in celiac disease pathology. According to him, an alternative is that Proteobacteria somehow boost the immune response to gluten or gliadin.