Celiac disease is a disease with many unknowns. A new field of explanations has been opened with evidence suggesting that celiac patients present a dysbiosis in the intestinal microbiota, which promotes the pro-inflammatory role of gluten.
Celiac disease is an autoimmune enteropathy secondary to the ingestion of gluten. Histologically, it is characterized by intestinal villous atrophy and an increase in intraepithelial lymphocytes. It affects around 1% of the population, but an increase has been observed in the incidence of this disease in recent years.1
Gluten and the intestinal epithelium
Although the pathophysiology remains partially unknown, some mechanisms have been determined: gliadin peptides (gluten proteins responsible for intolerance) are transported transcellularly through the intestinal epithelium via the CD71 receptor, which is the transferrin receptor. After their deamidation, these peptides activate T cells in the chorion and the synthesis of interferon-γ and interleukin-21, which have a harmful effect on the intestinal epithelium.2
Connection to dysbiosis
Although the impact of triggers has not yet been elucidated, epidemiological data suggest that bacterial or viral infections (gastroenteritis caused by rotavirus,3 Campylobacter jejuni infections4) play a role. The intestinal microbiota also seems to play a role in this pathophysiology. Changes in the microbiota were observed in celiac patients, with an abundance of Firmicutes and Proteobacteria, an increase in Gram-negative bacteria (Bacteroidetes and E. coli), and a reduction in anti-inflammatory bacteria like Bifidobacterium.4
Microbiota and probiotics
The composition of the microbiota may influence the individual response. The presence of Bifidobacterium may have an anti-inflammatory effect, and aid the digestion of gluten.5,6 Conversely, pro-inflammatory bacteria like E. coli may induce an increase in inflammation neurotransmitters, activate lymphocytes, and facilitate the transport of gliadin peptides.4 Current data suggest that celiac disease results from a combination of factors, including the host’s genetic profile, intestinal dysbiosis, and epigenetic changes that are still unknown.7 The only current treatment is the total eradication of gluten. Nevertheless, modulating the intestinal microbiota via probiotics is being considered, and is currently being studied in celiac patients.7,8
1. Catassi C. et al. The new epidemiology of celiac disease. J Pediatr Gastroenterol Nutr. 2014 Jul;59 Suppl 1:S7-9. https://www.ncbi.nlm.nih.gov/pubmed/24979197
2. Meresse B. et al. Celiac disease: an immunological jigsaw. Immunity 2012 ; 36 : 907-19. https://www.ncbi.nlm.nih.gov/pubmed/22749351
3. Stene LC et al. Rotavirus infection frequency and risk of celiac disease autoimmunity in early childhood: a longitudinal study. Am J Gastroenterol 2006 ; 101 : 2333-40. https://www.ncbi.nlm.nih.gov/pubmed/17032199
4. Verdu EF et al. Novel players in coeliac disease pathogenesis: role of the gut microbiota. Nat Rev Gastroenterol Hepatol 2015 ; 12 : 497-506. https://www.ncbi.nlm.nih.gov/pubmed/26055247
5. Laparra JM et al. Bifidobacteria inhibit the inflammatory response induced by gliadins in intestinal epithelial cells via modifications of toxic peptide generation during digestion. J Cell Biochem 2010 ; 109 : 801-7.
6. Cinova J et al. Role of intestinal bacteria in gliadin-induced changes in intestinal mucosa: study in germ-free rats. PLoS ONE 2011 ; 6 : e16169
7. Cenit MC et al. Intestinal Microbiota and Celiac Disease : Cause, Consequence or Co-Evolution? Nutrients. 2015 ; 7 : 6900-6923. doi:10.3390/nu7085314.
8. Olivares M et al. Double-blind, randomised, placebo-controlled intervention trial to evaluate the effects of Bifidobacterium longum CECT 7347 in children with newly diagnosed coeliac disease. Br J Nutr 2014 ; 112 : 30-40. https://www.ncbi.nlm.nih.gov/pubmed/24774670