Only a small proportion of individuals who are genetically susceptible to celiac disease actually develop the 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 intolerant to gluten – a protein found in grains including rye, wheat and barley. It is estimated that around 1% of the American population has celiac disease.
When an individual with celiac disease consumes gluten, the immune system responds by causing damage to the small intestine. This may lead to abdominal pain, diarrhea, bloating and fatigue, among other symptoms.
Certain gene mutations are known to trigger celiac disease. However, only 2-3% of people who possess such mutations actually develop the condition.
In an attempt to address why this is, lead investigator Dr. Elena F. Verdu, of the Digestive Health Research Institute at McMaster University in Canada, and colleagues looked at how the immune responses to gluten varied with different populations of gut bacteria in mouse models of gluten intolerance.
Their findings are published in The American Journal of Pathology.
Germ-free mice showed signs of celiac disease is response to gluten
The team assessed three groups of mice that expressed a gene called DQ8, which is found in humans and makes them genetically susceptible to gluten intolerance.
Fast 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.
Learn more about celiac disease
Each group of mice had different 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 remaining 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 exposed each group of mice to gluten. They found 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. Increased IEL levels, however, were not seen in the clean SPF mice.
What is more, the germ-free mice experienced increased death of cells that line the gastrointestinal tract, called enterocytes, alongside anatomical alterations of the small, fingerlike projections that line the small intestine, known as the villi.
The researchers also identified the development of antibodies in response to a component of gluten – called gliadin – among the germ-free mice, and these mice also demonstrated T-cell responses specific to this component.
Interestingly, the team found 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 received enteroadherent Escherichia coli from a patient with celiac disease.
Increasing Proteobacteria worsened gluten-induced pathology
Conventional SPF mice demonstrated greater gluten-induced pathology than clean SPF mice, according to the researchers, so the team set out to investigate whether the presence of Proteobacteria, such as Escherichia andHelicobacter, plays a role.
On increasing the presence of Proteobacteria among conventional SPF mice by administering an antibiotic called vancomycin around the time of their birth, the researchers found that gluten-induced pathology got worse. Specifically, the team identified an increase in 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.”
In an editorial linked to the study, Dr. Robin G. Lorenz, of the University of Alabama at Birmingham, notes that while these findings suggest the presence of Proteobacteria may play an important role in celiac disease pathology, they do not mean that Proteobacteria causes the condition. An alternative, he suggests, is that Proteobacteria somehow boost the immune response to gluten or gliadin.
Earlier this year, a study reported by Medical News Today suggested that individuals with celiac disease may be at greater risk for nerve damage.