From the AGA Journals

Study IDs microbial signature of celiac disease in children

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Microbial signature of celiac disease identified

It is well known that gluten ingestion in genetically susceptible individuals does not guarantee celiac disease, and research over the past decade has searched for environmental triggers. Gut microbiota play a role in activation of innate immunity, which leads to the adaptive immune response and the small bowel damage that is characteristic of celiac disease. The authors of this study sought to identify whether there is a distinct microbial pattern among celiac disease patients, both those with treated and untreated disease, in comparison with healthy controls and healthy siblings.

Dr. Dawn Wiese Adams, assistant professor, medical director, Center for Human Nutrition, department of gastroenterology, hepatology and nutrition, Vanderbilt University Medical Center, Nashville, Tenn

Dr. Dawn Wiese Adams

The authors identified three groups of bacterial taxa: 1) unique to celiac disease independent of treatment, 2) new-onset disease and treatment responsive, and 3) reflective of diet changes and not unique to disease. Within the first group, 11 distinct operational taxonomic units (OTUs) could highly predict celiac disease regardless of treatment. From these results, we cannot determine if the microbial signature is a result of disease or a contributor to disease development; however, it reinforces that this unique signature is present at diagnosis and identifies taxa for further investigation.

A significantly different microbial profile and metabolites were identified in subjects on gluten-free diets. The consequences of the gluten-free diet are an important consideration when committing a patient to this life-long therapy. The microbiome changes may play a role in persistent symptoms and the increased health conditions we see in treated celiac disease. Those on a gluten-free diet have other micronutrient deficiencies in addition to microbiome changes and the health sequelae of this are not fully understood. A gluten-free diet focused on restoring the normal gut flora through probiotic or gluten-free prebiotic or fiber supplementation in celiac disease patients could prove beneficial.

Dawn Wiese Adams, MD, MS, is assistant professor and medical director, Center for Human Nutrition, department of gastroenterology, hepatology, and nutrition, Vanderbilt University Medical Center, Nashville, Tenn. She has no conflicts of interest.



Eleven operational taxonomic units (OTUs) of fecal bacteria were less abundant in children with celiac disease than in healthy children, according to the findings of a study published in Gastroenterology.

Gluten-free bread in a bin chameleonseye/Thinkstock

This microbial signature correctly identified approximately four out of five cases of celiac disease, regardless of whether children were newly diagnosed or had already modified their diet, reported Konstantina Zafeiropoulou and Ben Nichols, PhD, of the Glasgow Royal Infirmary. “It is not clear whether the microbes identified [in this study] contribute to the pathogenesis of celiac disease or are the result of it. Future research should explore the role of the disease-specific species identified here,” the researchers wrote in Gastroenterology.

Celiac disease is multifactorial. While up to 40% of people are genetically predisposed, only a small proportion develop it, suggesting that environmental factors are key to pathogenesis. Recent studies have linked celiac disease with alterations in the gut microbiome, but it is unclear whether dysbiosis is pathogenic or a secondary effect of disease processes such as nutrient malabsorption, or whether dysbiosis is present at disease onset or results from a gluten-free diet.

For the study, the researchers performed gas chromatography and 16S ribosomal RNA sequencing of fecal samples from 141 children, including 20 with newly biopsy-confirmed, previously untreated celiac disease, 45 who were previously diagnosed and on a gluten-free diet, 19 unaffected siblings, and 57 healthy children who were not on regular medications and had no history of chronic gastrointestinal symptoms. A single fecal sample was tested for all but the previously untreated children, who were tested at baseline and then after 6 and 12 months on a gluten-free diet.

Children with new-onset celiac disease showed no evidence of dysbiosis, while a gluten-free diet explained up to 2.8% of variation in microbiota between patients and controls. Microbial alpha diversity, a measure of species-level diversity, was generally similar among groups, but between 3% and 5% of all taxa differed. Irrespective of treatment, the decreased abundance of the 11 OTUs was diagnostic for celiac disease with an error rate of 21.5% (P < .001 vs. random classification). Notably, most of these 11 discrepant OTUs were associated with nutrient or food group intake and with biomarkers of gluten ingestion, the researchers said. Gas chromatography showed that, after patients started a gluten-free diet, fecal levels of butyrate and ammonia decreased.

“Even though we identified differences in the abundance of a few species between patients with untreated celiac disease and healthy controls, the profound microbial dysbiosis noted in Crohn’s disease was not observed, at least using crude diversity indices,” the investigators commented. “Although several alterations in the intestinal microbiota of children with established celiac disease appear to be effects of a gluten-free diet, there are specific bacteria that are distinct biomarkers of celiac disease.”

Future research might involve performing in vitro tests of “candidate” bacteria, coculturing these bacteria with human immune cells, and studying whether dietary interventions alter the relative abundance of these bacteria in the gut microbiome, the researchers said.

Nutricia Research Foundation, the Biotechnology and Biological Sciences Research Council, and The Catherine McEwan Foundation provided funding. Three coinvestigators disclosed ties to Nutricia, 4D Pharma, AbbVie, Celltrion, Janssen, Takeda, and several other pharmaceutical companies. One coinvestigator reported chairing the working group for ISLI Europe. The remaining investigators reported having no conflicts of interest.

SOURCE: Zafeiropoulou K et al. Gastroenterology. 2020 Aug 10;S0016-5085(20)35023-X. doi: 10.1053/j.gastro.2020.08.007.

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