Thirty-three percent of people have a gene that predisposes them to celiac disease (CD), while only two to five percent of the population will receive a diagnosis of the condition. Elena Verdú, Associate Professor and researcher at McMaster University in Canada, wants to know why the unlucky minority end up with the disease. “We know that genes are necessary, but they’re not sufficient,” she says. “So there are other environmental factors that may play a role.”
In a person with CD, gluten triggers a complex set of processes in the body. The small intestine is the site of all the action: when enzymes begins to break down gluten proteins from the diet, the immune system goes on high alert. Immune cells are inappropriately activated, leading to intestinal damage and poor absorption of nutrients. Avoiding products that contain gluten is the only known way to manage the disease.
Verdú suspects the gut microbiota might be able to affect the immune reactions involved in celiac disease. For her team, the first clue that gut bacteria might be relevant was the observation that CD patients have a different set of intestinal bacteria than healthy people.
She then wondered: Would changing the gut microbiota make the disease get better or worse? Is there a particularly set of bacteria that could protect against the disease in people who were genetically predisposed? Since it was impossible to test these things experimentally in humans, Verdú turned to rodents.
The experimental mice used by Verdú’s team all had the gene that made them susceptible to a celiac-like disease in mice.
The researchers tested three groups: mice with no gut microbiota, mice with benign bacteria (a limited group that are known for maintaining balance in the gut), and mice with a normal, complex microbiota – including bacteria that had the potential to cause disease.
Verdú’s team found that bacteria could act as either friend or foe when it came to CD. Germ-free mice and those with a complex microbiota had increased reactions to gluten. But the mice colonized with benign bacteria had reduced reactions to gluten, indicating that the specially-selected bacterial mix had helped the mice activate protective immune responses.
The researchers then added one more kind of bacteria to the mice with the benign mix: a normally harmless bacteria that can cause disease under some circumstances (in other words, a pathobiont), which was isolated from a human with celiac disease. “In doing that, these mice now became susceptible to gluten. They were not protected anymore,” says Verdú. “It’s not only the presence or absence of bacteria that matters, it’s the balance between [harmless] commensals and pathobionts as well.”
Because the studies were carried out in mice, there are limits to how much they apply to humans. But they are a step toward finding out what is really happening. “We are starting to show that the alterations in gut microbiota that are being reported in human clinical studies are not merely associations — that there might be an immunomodulatory role of bacteria,” says Verdú. It could turn out that the normal bacteria the live in the human gut influence the immune system in a way that affects the course of celiac disease.
Verdú hopes to one day pinpoint the groups of bacteria that either speed up or slow down the immune activity of celiac disease. “You could envision that in families with celiac disease you could intervene somehow to try to reduce the risk,” she says. Perhaps by first understanding the ideal ecosystem of bacteria that reduce CD risk, and then adding probiotic strains to balance out the microbiota, prevention – “the holy grail” — would be within reach.