Celiac disease is an autoimmune disorder in which an individual is hypersensitive to gluten- a protein commonly found in grains such as rye, barley and wheat. According to statistics, about 1% of American population suffers from celiac disease.
When people who are gluten intolerant consume foods that contain gluten, the immune system reacts by causing damage to the small intestine. This can result in diarrhea, bloating, abdominal pain and fatigue.
There are various gene mutations that trigger celiac disease. But, just 2-3% of people who have these mutations actually develop this condition.
The lead researcher Dr. Elena F. Verdu of the Digestive Health Research Institute at McMaster University in Canada, and her colleagues, examined how the immune response to gluten varies with different populations of gut bacteria in mice with gluten hypersensitivity.
The results were published in The American Journal of Pathology.
Germ-free mice showed signs of celiac disease is response to gluten
The researchers analyzed three groups of mice that expressed a gene known as DQ8, which is also found in humans and makes them genetically prone to gluten intolerance.
Fast facts about celiac disease
- About 83% of American population with celiac disease is undiagnosed or misdiagnosed with other health conditions
- Gluten-free nutrition is the only treatment for celiac disease
- About 5-22% of individuals with celiac disease have a first-degree relative diagnosed with the disease.
Each group of mice models had different gut microbiomes. One group was germ-free, another was clean specific-pathogen-free (SPF), meaning their gut microbiomes were free of Proteobacteria- a group of gram-negative bacteria-and opportunistic pathogens.
The final group were mice with conventional SPF, meaning they possessed a wide range of gut bacteria, including protozoan pathogens (opportunistic pathogens) like Staphylococcus, Streptococcus and Helicobacter.
Each group of mice was exposed to gluten. The results have shown that germ-free mice had increased levels of intraepithelial lymphocytes (IELs) in the gut. Activation and reproduction of IELs is the primary indicator of celiac disease. On the other hand, there were not increased IEL levels in the clean SPF mice.
Moreover, in the germ-free mice was also noted a higher rate of cell death in the line of the gastrointestinal tract, known as enterocytes, along with the anatomical changes in the small structures that line the small intestine, called villi.
The research team also noted the development of antibodies as a response to a component of gluten-called gliadin- in the germ-free group of mice. In addition, these mice also showed T-cell responses specific to this component.
Furthermore, the researchers found that gluten-induced immune responses were stopped in the clean SPF mice in comparison to the germ-free mice. However, this was not the case when the clean SPF mice were given enteroadherent Escherichia coli from a patient with celiac disease.
Increasing Proteobacteria worsened gluten-induced pathology
According to the researchers, mice with conventional SPD showed greater gluten-induced pathology when compared to clean SPF mice, so they decided to investigate whether the presence of Proteobacteria, such as Escherichia and Helicobacter, has some impact.
Conventional SPF mice which received antibiotic called vancomycin to increase the presence of Proteobacteria experienced worsened gluten-induced pathology. Also, the researchers found increased levels of IELs.
“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,” says Dr. Verdu, adding:
“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.”
However, Dr. Robin G. Lorenz of the University of Alabama at Birmingham reported in an editorial related to the study that the presence of Proteobacteria has a significant impact on celiac disease pathology, but this does not mean that Proteobacteria are the cause of this disorder. More precisely, Proteobacteria stimulate the immune response to gluten or giladin.