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Dysbiosis a risk factor for celiac disease

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Abstract

Celiac disease remains one of the most challenging pathologies of the small intestine. It involves multiple pathogenic pathways and there are no disease-changing pharmacological agents available against it yet. The term microbiota refers to the community of microorganisms that inhabit a particular region of the body. Normal gut microbiota has a vital role in maintaining the intestinal homeostasis and promoting health. Celiac disease is associated with microbiota alteration, especially with an increase in the number of Gram-negative bacteria and a decrease in the number of Gram-positive bacteria. There is a strong relationship between intestinal dysbiosis and celiac disease, and recent studies are aimed at determining whether the celiac disease is a risk factor for dysbiosis or dysbiosis is for celiac disease. Therefore, the aim of this review was to assess the latest findings regarding the gut microbiota and its impact on the celiac disease, including therapeutic aspects.

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References

  1. Bai JC, Fried M, Corazza GR et al (2013) World Gastroenterology Organisation global guidelines on celiac disease. J Clin Gastroenterol 47:121–126

    Article  PubMed  Google Scholar 

  2. Frank DN, St Amand AL, Feldman RA et al (2007) Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci USA 104:13780–13785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Jandhyala SM, Talukdar R, Subramanyam C et al (2015) Role of the normal gut microbiota. World J Gastroenterol 21:8787–8803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Nagao-Kitamoto H, Kitamoto S, Kuffa P et al (2016) Pathogenic role of the gut microbiota in gastrointestinal diseases. Intest Res 14:127–138

    Article  PubMed  PubMed Central  Google Scholar 

  5. De Palma G, Capilla A, Nadal I et al (2010) Interplay between human leukocyte antigen genes and the microbial colonization process of the newborn intestine. Curr Issues Mol Biol 12:1–10

    PubMed  Google Scholar 

  6. Palma GD, Capilla A, Nova E et al (2012) Influence of milk-feeding type and genetic risk of developing coeliac disease on intestinal microbiota of infants: the PROFICEL study. PloS One 7:e30791

    Article  PubMed  PubMed Central  Google Scholar 

  7. Olivares M, Laparra JM, Sanz Y (2013) Host genotype, intestinal microbiota and inflammatory disorders. Br J Nutr 109:S76–S80

    Article  CAS  PubMed  Google Scholar 

  8. Olivares M, Neef A, Castillejo G et al (2015) The HLA-DQ2 genotype selects for early intestinal microbiota composition in infants at high risk of developing coeliac disease. Gut 64:406–417

    Article  CAS  PubMed  Google Scholar 

  9. Kupfer S, Jabri B (2012) Pathophysiology of celiac disease. Gastrointest Endosc Clin N Am 22:639–660

    Article  PubMed  Google Scholar 

  10. Barker JM, Liu E (2008) Celiac disease: pathophysiology, clinical manifestations and associated autoimmune conditions. Adv Pediatr 55:349–365

    Article  PubMed  PubMed Central  Google Scholar 

  11. Garrote JA, Gómez-González E, Bernardo D et al (2008) Celiac disease pathogenesis: the proinflammatory cytokine network. J Pediatr Gastroenterol Nutr 47:S27–S32

    Article  CAS  PubMed  Google Scholar 

  12. Sarno M, Discepolo V, Troncone R et al (2015) Risk factors for celiac disease. Ital J Pediatr 41:57

    Article  PubMed  PubMed Central  Google Scholar 

  13. Icaza-Chavez ME (2013) Gut microbiota in health and disease. Rev Gastroenterol Mex 78:240–248

    CAS  PubMed  Google Scholar 

  14. Bustos Fernandez LM, Lasa JS et al (2014) Intestinal microbiota: its role in digestive diseases. J Clin Gastroenterol 48:657–666

    Article  PubMed  Google Scholar 

  15. McLean MH, Dieguez D Jr, Miller LM et al (2015) Does the microbiota play a role in the pathogenesis of autoimmune diseases? Gut 64:332–341

    Article  CAS  PubMed  Google Scholar 

  16. Carding S, Verbeke K, Vipond DT et al (2015) Dysbiosis of the gut microbiota in disease. Microb Ecol Health Dis 26:26191

    PubMed  Google Scholar 

  17. Ou G, Hedberg M, Horstedt P, Baranov V et al (2009) Proximal small intestinal microbiota and identification of rod-shaped bacteria associated with childhood celiac disease. Am J Gastroenterol 104:3058–3067

    Article  PubMed  Google Scholar 

  18. Cinova J, De Palma G, Stepankova R et al (2011) Role of intestinal bacteria in gliadin-induced changes in intestinal mucosa: study in germ-free rats. PloS One 6:e16169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kalliomaki M, Satokari R, Lahteenoja H et al (2012) Expression of microbiota, Toll-like receptors, and their regulators in the small intestinal mucosa in celiac disease. J Pediatr Gastroenterol Nutr 54:727–732

    Article  PubMed  Google Scholar 

  20. Cheng J, Kalliomaki M, Heilig HG et al (2013) Duodenal microbiota composition and mucosal homeostasis in pediatric celiac disease. BMC Gastroenterol 13:113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. De Palma G, Kamanova J, Cinova J et al (2012) Modulation of phenotypic and functional maturation of dendritic cells by intestinal bacteria and gliadin: relevance for celiac disease. J Leukoc Biol 92:1043–1054

    Article  PubMed  Google Scholar 

  22. Sjoberg V, Sandstrom O, Hedberg M et al (2013) Intestinal T-cell responses in celiac disease - impact of celiac disease associated bacteria. PloS One 8:e53414

    Article  PubMed  PubMed Central  Google Scholar 

  23. Hawrelak J, Myers S (2004) The causes of intestinal dysbiosis: a review. Altern Med Rev 9:180–197

    PubMed  Google Scholar 

  24. Marild K, Ye W, Lebwohl B et al (2013) Antibiotic exposure and the development of coeliac disease: a nationwide case-control study. BMC Gastroenterol 13:109

    Article  PubMed  PubMed Central  Google Scholar 

  25. Galipeau HJ, McCarville JL, Huebener S et al (2015) Intestinal microbiota modulates gluten-induced immunopathology in humanized mice. Am J Pathol 185:2969–2982

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Galipeau HJ, Verdu EF (2014) Gut microbes and adverse food reactions: focus on gluten related disorders. Gut Microbes 5:594–605

    Article  PubMed  PubMed Central  Google Scholar 

  27. Caminero A, Galipeau HJ, McCarville JL et al (2016) Duodenal bacteria from patients with celiac disease and healthy subjects distinctly affect gluten breakdown and immunogenicity. Gastroenterology 151:670–683

    Article  CAS  PubMed  Google Scholar 

  28. Moran C, Sheehan D, Shanahan F (2015) The small bowel microbiota. Curr Opin Gastroenterol 31:130–136

    Article  CAS  PubMed  Google Scholar 

  29. Cenit MC, Olivares M, Codoner-Franch P et al (2015) Intestinal microbiota and celiac disease: cause, consequence or co-evolution? Nutrients 7:6900–6923

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Sánchez E, Nadal I, Donat E et al (2008) Reduced diversity and increased virulence-gene carriage in intestinal enterobacteria of coeliac children. BMC Gastroenterol 8:50

    Article  PubMed  PubMed Central  Google Scholar 

  31. Sanchez E, Ribes-Koninckx C, Calabuig M et al (2012) Intestinal Staphylococcus spp. and virulent features associated with coeliac disease. J Clin Pathol 65:830–834

    Article  CAS  PubMed  Google Scholar 

  32. Collado MC, Donat E, Ribes-Koninckx C et al (2009) Specific duodenal and faecal bacterial groups associated with paediatric coeliac disease. J Clin Pathol 62:264–269

    Article  CAS  PubMed  Google Scholar 

  33. Schippa S, Iebba V, Barbato M et al (2010) A distinctive ‘microbial signature’ in celiac pediatric patients. BMC Microbiol 10:175

    Article  PubMed  PubMed Central  Google Scholar 

  34. Di Cagno R, De Angelis M, De Pasquale I et al (2011) Duodenal and faecal microbiota of celiac children: molecular, phenotype and metabolome characterization. BMC Microbiol 11:219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Sanchez E, Donat E, Ribes-Koninckx C et al (2013) Duodenal-mucosal bacteria associated with celiac disease in children. Appl Environ Microbiol 79:5472–5479

    Article  PubMed  PubMed Central  Google Scholar 

  36. Francavilla R, Ercolini D, Piccolo M et al (2014) Salivary microbiota and metabolome associated with celiac disease. Appl Environ Microbiol 80:3416–3425

    Article  PubMed  PubMed Central  Google Scholar 

  37. Giron Fernandez-Crehuet F, Tapia-Paniagua S, Morinigo Gutierrez MA et al (2016) The duodenal microbiota composition in children with active coeliac disease is influenced by the degree of enteropathy. An Pediatr (Barc) 84:224–230

    Article  CAS  Google Scholar 

  38. D’Argenio V, Casaburi G, Precone V et al (2016) Metagenomics reveals dysbiosis and a potentially pathogenic N. flavescens strain in duodenum of adult celiac patients. Am J Gastroenterol 111:879–890

    Article  PubMed  PubMed Central  Google Scholar 

  39. Nistal E, Caminero A, Herran AR et al (2012) Differences of small intestinal bacteria populations in adults and children with/without celiac disease: effect of age, gluten diet, and disease. Inflamm Bowel Dis 18:649–656

    Article  PubMed  Google Scholar 

  40. Bonder MJ, Tigchelaar EF, Cai X et al (2016) The influence of a short-term gluten-free diet on the human gut microbiome. Genome Med 8:45

    Article  PubMed  PubMed Central  Google Scholar 

  41. Nistal E, Caminero A, Vivas S et al (2012) Differences in faecal bacteria populations and faecal bacteria metabolism in healthy adults and celiac disease patients. Biochimie 94:1724–1729

    Article  CAS  PubMed  Google Scholar 

  42. Golfetto L, de Senna FD, Hermes J et al (2014) Lower bifidobacteria counts in adult patients with celiac disease on a gluten-free diet. Arq Gastroenterol 51:139–143

    Article  PubMed  Google Scholar 

  43. Wacklin P, Laurikka P, Lindfors K et al (2014) Altered duodenal microbiota composition in celiac disease patients suffering from persistent symptoms on a long-term gluten-free diet. Am J Gastroenterol 109:1933–1941

    Article  CAS  PubMed  Google Scholar 

  44. Wacklin P, Kaukinen K, Tuovinen E, et al (2013) The duodenal microbiota composition of adult celiac disease patients is associated with the clinical manifestation of the disease. Inflamm Bowel Dis 2013;19:934–941

    Article  PubMed  Google Scholar 

  45. Pozo-Rubio T, Olivares M, Nova E et al (2012) Immune development and intestinal microbiota in celiac disease. Clin Dev Immunol 2012:654143

    Article  PubMed  PubMed Central  Google Scholar 

  46. Pozo-Rubio TG, Mujico JR, Olivares M et al (2013) Influence of early environmental factors on lymphocyte subsets and gut microbiota in infants at risk of celiac disease; the PROFICEL study. Nutr Hosp 28:464–473

    PubMed  Google Scholar 

  47. Ivanov II, Honda K (2012) Intestinal commensal microbes as immune modulators. Cell Host Microbe 12:496–508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Gerald Friedman (2012) Clinical applications of probiotics in gastroenterology: questions and answers, an issue of gastroenterology clinics. Saunders, United States

    Google Scholar 

  49. Fons M, Gomez A (2000) Mechanisms of colonisation and colonisation resistance of the digestive tract. Microbial Ecol Health Dis 12:240–246

    Article  Google Scholar 

  50. Hardy H, Harris J, Lyon E et al (2013) Probiotics, prebiotics and immunomodulation of gut mucosal defences: homeostasis and immunopathology. Nutrients 5:1869–1912

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Sherman PM, Ossa JC, Johnson-Henry K (2009) Unraveling mechanisms of action of probiotics. Nutr Clin Pract 24:10–14

    Article  PubMed  Google Scholar 

  52. Iebba V, Santangelo F, Totino V et al (2013) Higher prevalence and abundance of Bdellovibrio bacteriovorus in the human gut of healthy subjects. PloS One 8:e61608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. De Sousa Moraes LF, Grzeskowiak LM, de Sales Teixeira TF et al (2014) Intestinal microbiota and probiotics in celiac disease. Clin Microbiol Rev 27:482–489

    Article  Google Scholar 

  54. Olivares M, Castillejo G, Varea V et al (2014) 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 112:30–40

    Article  CAS  PubMed  Google Scholar 

  55. Lorenzo Pisarello MJ, Vintini EO, Gonzalez SN et al (2015) Decrease in lactobacilli in the intestinal microbiota of celiac children with a gluten-free diet, and selection of potentially probiotic strains. Can J Microbiol 61:32–37

    Article  CAS  PubMed  Google Scholar 

  56. Klemenak M, Dolinsek J, Langerholc T et al (2015) Administration of bifidobacterium breve decreases the production of TNF-alpha in children with celiac disease. Dig Dis Sci 60:3386–3392

    Article  CAS  PubMed  Google Scholar 

  57. Wei G, Tian N, Valery AC et al (2015) Identification of pseudolysin (lasB) as an aciduric gluten-degrading enzyme with high therapeutic potential for celiac disease. Am J Gastroenterol 110:899–908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Mohammadi R, Hosseini-Safa A, Ehsani Ardakani MJ et al (2015) The relationship between intestinal parasites and some immune-mediated intestinal conditions. Gastroenterol Hepatol Bed Bench 8:123–131

    PubMed  PubMed Central  Google Scholar 

  59. Croese J, Giacomin P, Navarro S et al (2015) Experimental hookworm infection and gluten microchallenge promote tolerance in celiac disease. J Allergy Clin Immunol 135:508–516

    Article  CAS  PubMed  Google Scholar 

  60. Giacomin P, Zakrzewski M, Croese J et al (2015) Experimental hookworm infection and escalating gluten challenges are associated with increased microbial richness in celiac subjects. Sci Rep 5:13797

    Article  PubMed  PubMed Central  Google Scholar 

  61. Kverka M, Tlaskalova-Hogenova H (2013) Two faces of microbiota in inflammatory and autoimmune diseases: triggers and drugs. APMIS 121:403–421

    Article  CAS  PubMed  Google Scholar 

  62. Conlon AM, Bird AR (2015) The impact of diet and lifestyle on gut microbiota and human health. Nutrients 7:17–44

    Article  Google Scholar 

  63. De Angelis M, Vannini L, Di Cagno R et al (2016) Salivary and fecal microbiota and metabolome of celiac children under gluten-free diet. Int J Food Microbiol 19(239):125–132

    Article  Google Scholar 

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Acknowledgements

The first author received a grant from the University of Medicine and Pharmacy “Iuliu Hațieganu” Cluj–Napoca 2016, project no. 4995/21/08.03.2016.

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Correspondence to Gabriel Samasca.

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Girbovan, A., Sur, G., Samasca, G. et al. Dysbiosis a risk factor for celiac disease. Med Microbiol Immunol 206, 83–91 (2017). https://doi.org/10.1007/s00430-017-0496-z

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