New study links gut makeup to celiac disease development

Specific genetic architecture in the gut microbial ecosystem can shape microbial composition in ways that are potentially relevant to the pathogenesis of celiac disease, according to a study published this month in Nature Genetics.

As MedCentral recently reported, although the community of micro-organisms in the gastrointestinal (GI) tract, also known as the gut microbiota, is associated with many diseases — and research suggests that genetic predisposition may play a role — no specific microbial species has been consistently shown to drive the progression of celiac disease, a GI condition characterized by the loss of gluten tolerance. 

“Overall, the HUNT study is very fascinating, bringing to light the delicate interplay of genetic predisposition and the microbiome,” Susan S. Kais, MD, a gastroenterologist and assistant professor of clinical medicine at the University of Cincinnati College of Medicine, told MedCentral. “To date, our understanding has been that celiac disease is due to gluten intolerance driven by a person’s genetic predisposition and not much has been discussed about the role of microbiomes and the development of celiac disease. Now we know that if the diagnosis is questionable despite testing and duodenal biopsies — the gold standard of diagnosis — then we can order HLA-DQ2 and HLA-DQ8 genotyping to confirm the diagnosis.” Kais was not involved in the study.

Kais told MedCentral the HUNT study raises a valid hypothesis about this genetic-microbiome interplay, but there is no exact mechanism for it to date.

“A dysregulated microbiome may disrupt the balance of immune responses, leading to an inappropriate reaction to gluten in genetically predisposed individuals. The presence of beneficial bacteria, such as Agathobacter, may support immune balance, whereas their reduced microbial diversity may increase susceptibility to celiac disease,” she explained. “This remains a hypothesis too early to be implemented clinically, and more studies are needed.”

Kais, a faculty member in the Division of Gastroenterology and Hepatology in the Department of Internal Medicine, emphasized the HUNT study findings encourage clinicians to look beyond current understanding of how genetics and microbiomes affect celiac disease, adding that physicians should consider screening individuals with specific genetic markers and assessing their gut microbiota composition to support early detection and risk stratification for celiac disease.

“For those at risk of the disease, preventive strategies may include modulating the gut microbiota through a high-fiber diet and recommending personalized microbiome therapies, such as probiotics or prebiotics, to enhance protective Agathobacter sp. activity,” she concluded.

Read the full MedCentral article.

Featured image at top: iStock/seb_ra.