Celiac disease is an autoimmune condition involving an immune reaction that is triggered by dietary gluten, found in wheat, barley and rye. Partially digested gluten peptides can trigger symptoms in genetically susceptible individuals, expressing HLA-DQ2 or DQ8 genes. While necessary for disease development, the expression of DQ2/DQ8 is not sufficient for disease development, suggesting a critical role for environmental factors. Alterations in the intestinal microbial composition have been described in celiac disease, but a clear microbial signature hasn’t been defined and the pathophysiological significance of these alterations is unknown.

Gluten is highly resistant to digestion by human digestive enzymes; however, digestion of gluten by intestinal bacteria has recently been described. In a recently published paper in Gastroenterology, a group led by Dr. Elena Verdú at McMaster University explored how bacteria isolated from celiac disease patients and healthy controls differentially influence gluten digestion and the immunogenicity of gluten metabolism products.

Using germ-free mice colonized with either opportunistic pathogens, such as Pseudomonas aeruginosa, or commensals, such as Lactobacillus, Caminero et al first demonstrated that different bacteria can participate in gluten metabolism in vivo, and that they have distinct proteolytic activities.

The present study made use of Pseudomonas aeruginosa, an opportunistic pathogen in the small intestine, which was unique to celiac disease patients. The authors showed, in vitro, that P. aeruginosa, through its elastase activity, degrades gluten to produce immunogenic gluten peptides that can stimulate gluten-specific T cells from HLA-DQ2 celiac disease patients. Interestingly, these P. aeruginosa-digested gluten peptides were able to translocate across the small intestinal barrier more efficiently than those peptides digested by human proteases.

Increased antigen uptake can lead to greater antigen availability and may perpetuate immune responses in the small intestine. In contrast to P. aeruginosa, Lactobacillus spp isolated from the small intestines of healthy controls degraded gluten peptides that were generated by P. aeruginosa or human proteases into non-immunogenic peptides.

These findings suggest both opportunistic pathogens and commensal bacteria participate in gluten metabolism, but they generate distinct patterns of gluten peptides following digestion, which are associated with increased or decreased immunogenicity. The authors describe an important mechanism through which opportunistic pathogens, such as P. aeruginosa, may modify the pool of gluten peptides in the gut and increase susceptibility to celiac disease. Importantly, the gut is colonized with other bacteria and opportunistic pathogens, in addition to those described by Caminero et al, that can digest gluten and may also modify celiac disease risk in genetically susceptible individuals. Further insight into how this microbe-gluten-host interaction in celiac disease contributes to pathogenesis may provide exciting new therapeutic interventions, and may also explain the reported dysbiosis in celiac disease patients.




Caminero A, Galipeau HJ, McCarville JL, et al. Duodenal bacteria from patients with celiac disease and healthy subjects distinctly affect gluten breakdown and immunogenicity. Gastroenterology. 2016; 151(4):670-83.