Researchers from Mass General for Children (MGfC) and 13 other institutions have identified a strain of Bacteroides vulgatus that may protect the gut intestinal barrier against the break of tolerance that occurs when gluten is introduced into the diet of genetically at-risk children.
- Sue Flaherty, massgeneral.org/news 1
- Senior Author, Alessio Fasano, MD
In collaboration with researchers from Ohio, Italy and Spain, members of the Mucosal Immunology and Biology Research Center (MIBRC) at MGfC published the proof-of-concept study.
The article in Pediatric Research represents the most recent findings from a ten-year longitudinal, prospective study called the Celiac Disease Genomic, Environmental, Microbiome and Metabolomic Study (CDGEMM), which contains voluminous environmental and genomic data and biological samples from approximately 600 infants and children in the US, Italy and Spain.
CDGEMM researchers have completed several deep genomic analyses of the epigenetic profiling of several bacterial species in the small intestine of infants and children at risk of celiac disease. Now they have added functional studies to their research portfolio to test the effects of gluten on the gut microbiome.
Using tissue samples from children genetically predisposed to develop celiac disease and healthy controls, the researchers employed a human gut organoid model developed by Stefania Senger, PhD, at the Intestinal Organoid Program at MIBRC.
Researchers identified five microbial strains that appeared to play a protective role against the development of celiac disease, an autoimmune condition that occurs in roughly one percent of the US population.
In genetically predisposed individuals, eating products that contain wheat, rye or barley can initiate a cascade of events that results in a loosening of the barrier between intestinal epithelial cells and the passage of the gluten peptide.
The outcome is a blunting of the villi in the small intestine, which can lead to nutritional deficiencies and symptoms that can affect various body systems.
When gluten was introduced to the gut samples grown from tissue taken during endoscopies from the small intestine, it resulted in intestinal permeability, an increase in inflammatory cytokines and cell death.
The introduction of B. Vulgatus into the affected organoids resulted in improvement in these three factors through epigenetic reprogramming of the inflammatory pathways that control antigen trafficking.
- “Although it is only a small sample of four organoids, our findings are significant in identifying the mechanisms that precede the development of the autoimmune condition of celiac disease,”
In the article, the researchers state that “gut dysbiosis precedes the onset of celiac disease in genetically at-risk infants. This dysbiosis is characterized by the loss of protective bacterial strains in those children who will go on to develop celiac disease.”
Fasano notes that the ultimate goal of this comprehensive research program is to prevent celiac disease from occurring by manipulating the microbial makeup of the infant gut microbiome in the early march from genetic predisposition to full-blown celiac disease.
“Our data offer possible preliminary evidence that could lead to potential targets to interrupt the progression of celiac disease in people at risk with an unbalanced gut microbiome,” says Fasano. “Using celiac disease as a model, this line of research also holds promise for other autoimmune conditions.”
Research funding was provided by the National Institute of Allergy and Infectious Diseases Award Number R56AI169645 and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) DK109620 and K23DK122127. Additional support for came from the NIDDK grant Nutrition Obesity Research Center at Harvard 2P30DK040561-26.
Participating institutions include: NICU, University of Bari, Italy; Pediatric Unit “Bruno Trambusti,” Osp Pediatrico Giovanni XXIII, University of Bari, Italy; Pediatrics, IRCCS Ospedale Giannina Gaslini, Genova, Italy; Digestive Health Research Institute, Case Western Reserve University School of Medicine, Cleveland, OH; Department of Pathology, Case Western University School of Medicine, Cleveland OH; Celiac Disease Referral Center, Ospedale Maggiore Policlinico, Milan, Italy; Pediatric Gastroenterology Unit, Policlinico Umberto I, Sapienza University of Rome, Italy; Pediatric training program, University of Salerno School of Medicine, Salerno, Italy; Pediatric Hepatology Gastroenterology and Transplant Unit, Ospedale Papa Giovanni XXIII Bergamo, Italy; Celiac Disease Referral Center, “San Giovanni di Dio e Ruggi d’Aragona” University Hospital, Pole of Cava de’ Tirreni, Salerno, Italy; NICU, Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico, University of Milan, Italy; Pediatric Gastroenterology and Liver Unit, Santobono-Pausilipon Children’s Hospital, Naples, Italy; and the European Biomedical Research Institute of Salerno, Salerno, Italy.