Published On September 22, 2014
Alessio Fasano, chief of pediatric gastroenterology at MassGeneral Hospital for Children, thought he had celiac disease all figured out. It’s an autoimmune disease in which the body destroys its own cells—in this case, the cells lining the intestines—which causes digestive problems and sometimes leads to malnutrition and other serious health issues. As described in “Celiac Disease: Eating Away at You” (Winter 2010), celiac disease rests on a three-legged stool of genetic predisposition, an environmental trigger and the immune system’s misguided response in which it attacks the body. The easiest, most effective treatment is to eliminate the environmental irritant—gluten, an indigestible protein in wheat and other grains. Stop eating gluten and the symptoms of celiac disease are likely to disappear.
Fasano, who is also the director of the Center for Celiac Research at Massachusetts General Hospital, was puzzled by certain aspects of his own research—for instance, that only one in 10 of those who had the genes associated with celiac disease actually developed the disorder. Fasano now thinks the answers may lie in a provocative idea first proposed 10 years ago by Yolanda Sanz, a professor of celiac research with the Spanish National Research Council in Valencia, Spain.
Sanz was investigating the relationship between celiac disease and the gut’s bacterial communities. She compared gut microbiota in three groups of children: those with active celiac disease who weren’t yet avoiding gluten; kids with prior celiac disease (who had been on a gluten-free diet for at least one year); and healthy controls who didn’t have the celiac genes. The children with celiac disease had a higher than normal ratio of certain bacteria (some species of Bacteroides and virulent strains of E. coli) to other, more beneficial kinds (Bifidobacterium and Lactobacillus). Sanz found this microbial imbalance, called dysbiosis, even in the kids who were eating a gluten-free diet and had their celiac symptoms under control. A 2014 study by her lab now suggests that dysbiosis is not just a result of celiac disease but something that comes with the genetic territory. That imbalance may instigate the inflammation that is a hallmark of celiac.
“You can think of the genes as the keys of a piano,” Fasano says. “The bacteria in the gut are the players.” With dysbiosis, some bacteria hit predisposing genes and cause the disease. Other bacteria don’t play those genes, letting someone stay healthy while eating pasta—unless or until some change in the microbiota plays the discordant keys.
In 2014, Sanz published a trial in which she gave children with newly-diagnosed celiac disease a probiotic treatment while a control group got a placebo pill. In the kids who received the bacteria, the intervention successfully shifted the microbiota away from the pro-inflammatory bacterial populations. She’s now looking at whether this approach could help prevent celiac in children who have the predisposing genes or alleviate symptoms in those who already have the disease.
Fasano and colleagues at Harvard Medical School and affiliated hospitals have begun enrolling 500 at-risk infants to examine their genetics, diet and feeding patterns, gut microbiota and bacterial by-products that might signal when they’re about to get celiac disease and could be treated with a customized probiotic.
With researchers continuing to explore the implications of the microbiome as a trigger and other leads, the science of celiac turns out to be far from settled after all.
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