Çocuk Çölyak Hastalarında Glutensiz Diyet ve Mikrobiyota Odaklı Tedavilerin İntestinal Mikrobiyotaya Etkisi

Çölyak hastalığı genetik yatkınlığı bulunan bireylerde gluten tüketimini izleyen dönemde ciddi gastrointestinal veya ekstraintestinal sistem bozuklukları ile seyreden ince bağırsağın bir hastalığıdır. Hastalığın patogenezinde genetik etmenlerin yanı sıra çevresel faktörlerin rol oynadığı düşünülmektedir. Son yıllarda intestinal mikrobiyotadaki değişimlerin çölyak hastalığının patogenezindeki yeri gösterilmeye ve potansiyel girişimsel olmayan tedaviler için ipuçları sağlanmaya çalışılmaktadır. Yapılan çalışmalar çölyağın aktif ve tedavi altındaki dönemlerinde mikrobiyota değişimleri olduğunu göstermektedir. Ancak, çölyağın tedavisinde kullanılan glutensiz diyetlerin de bu değişimlere katkıda bulunduğuna dair araştırmalar mevcuttur. Dolayısıyla, intestinal mikrobiyotanın modülasyonunda konakçı, diyet ve immün sistem etkileşimlerinin bir arada değerlendirilmesi gerekmektedir. Bu derleme ile çocuk çölyak hastalarında glutensiz diyet ve mikrobiyota odaklı tedavilerin intestinal mikrobiyotaya etkisi incelenmiştir.

The Effect of Gluten-free Diet and Microbiota Focused Treatment on Microbiota Alterations in Children with Celiac Disease

Celiac is a small intestine disease with severe gastrointestinal or extraintestinal disorders following gluten consumption in individuals with genetic predisposition. Along with genetic factors, environmental factors are thought to play a role in the pathogenesis of the disease. In recent years, the role of alterations in intestinal microbiota in the pathogenesis of celiac disease has been shown and clues have been provided for potential non-invasive treatments. Studies show microbiota alterations during active and treatment periods of celiac. However, there is evidence showing that gluten-free diets may also contribute to these alterations. Therefore, host, diet and immune system interactions should be evaluated in modulation of intestinal microbiota. In this review, the effect of gluten-free diet and microbiota-focused therapies on intestinal microbiota in pediatric celiac patients was evaluated.

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1. Husby S, Koletzko S, Korponay-Szabo I, Mearin M, Phillips A, Shamir R, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr. 2012;54(1):136-60.
2. Dalgic B, Sari S, Basturk B, Ensari A, Egritas O, Bukulmez A, et al. Prevalence of celiac disease in healthy Turkish school children. Am J Gastroenterol. 2011;106(8):1512-7.
3. Chander AM, Yadav H, Jain S, Bhadada SK, Dhawan DK. Cross-talk between gluten, intestinal microbiota and intestinal mucosa in celiac disease: Recent advances and basis of autoimmunity. Front Microbiol. 2018;9:2597.
4. Lindfors K, Ciacci C, Kurppa K, Lundin KEA, Makharia GK, Mearin ML, et al. Coeliac disease. Nat Rev Dis Primers. 2019;5(1):3.
5. Shan L, Molberg Ø, Parrot I, Hausch F, Filiz F, Gray GM, et al. Structural basis for gluten intolerance in celiac sprue. Science. 2002;297(5590):2275-9.
6. Lebwohl B, Sanders DS, Green PH. Coeliac disease. The Lancet. 2018;391(10115):70-81.
7. Kagnoff MF. Overview and pathogenesis of celiac disease. Gastroenterology. 2005;128(4):S10-S18.
8. Rossi M, Schwartz KB. Celiac disease and intestinal bacteria: not only gluten? J Leukoc Biol. 2010;87(5):749- 51.
9. Verdu EF, Galipeau HJ, Jabri B. Novel players in coeliac disease pathogenesis: role of the gut microbiota. Nat Rev Gastroenterol Hepatol. 2015;12(9):497-506.
10. Collado MC, Calabuig M, Sanz Y. Differences between the fecal microbiota of coeliac Infants and healthy controls. Curr Issues Intest Microbiol. 2007;8(1): 9–14.
11. Nadal I, Donat E, Ribes-Koninckx C, Calabuig M, Sanz Y. Imbalance in the composition of the duodenal microbiota of children with coeliac disease. J Med Microbiol. 2007;56(Pt 12):1669-74.
12. Sanz Y, Sanchez E, Marzotto M, Calabuig M, Torriani S, Dellaglio F. Differences in faecal bacterial communities in coeliac and healthy children as detected by PCR and denaturing gradient gel electrophoresis. FEMS Immunol Med Microbiol. 2007;51(3):562-8.
13. Collado MC, Donat E, Ribes-Koninckx C, Calabuig M, Sanz Y. Imbalances in faecal and duodenal Bifidobacterium species composition in active and non-active coeliac disease. BMC Microbiol. 2008;8:232.
14. Collado MC, Donat E, Ribes-Koninckx C, Calabuig M, Sanz Y. Specific duodenal and faecal bacterial groups associated with paediatric coeliac disease. J Clin Pathol. 2009;62(3):264-9.
15. Di Cagno R, Rizzello CG, Gagliardi F, Ricciuti P, Ndagijimana M, Francavilla R, et al. Different fecal microbiotas and volatile organic compounds in treated and untreated children with celiac disease. Appl Environ Microbiol. 2009;75(12):3963-71.
16. Schippa S, Iebba V, Barbato M, Di Nardo G, Totino V, Checchi MP, et al. A distinctive ‘microbial signature’ in celiac pediatric patients. BMC Microbiol. 2010;10:175.
17. Di Cagno R, De Angelis M, De Pasquale I, Ndagijimana M, Vernocchi P, Ricciuti P, et al. Duodenal and faecal microbiota of celiac children: molecular, phenotype and metabolome characterization. BMC Microbiol. 2011;11:219.
18. Sanchez E, Laparra JM, Sanz Y. Discerning the role of Bacteroides fragilis in celiac disease pathogenesis. Appl Environ Microbiol. 2012;78(18):6507-15.
19. Sanchez E, Donat E, Ribes-Koninckx C, Fernandez-Murga ML, Sanz Y. Duodenal-mucosal bacteria associated with celiac disease in children. Appl Environ Microbiol. 2013;79(18):5472-9.
20. Tjellstrom B, Hogberg L, Stenhammar L, Falth- Magnusson K, Magnusson KE, Norin E, et al. Faecal short-chain fatty acid pattern in childhood coeliac disease is normalised after more than one year’s glutenfree diet. Microb Ecol Health Dis. 2013;24.
21. Wacklin P, Kaukinen K, Tuovinen E, Collin P, Lindfors K, Partanen J, et al. The duodenal microbiota composition of adult celiac disease patients is associated with the clinical manifestation of the disease. Inflamm Bowel Dis. 2013;19(5):934-41.
22. Olivares M, Walker AW, Capilla A, Benítez-Páez A, Palau F, Parkhill J, et al. Gut microbiota trajectory in early life may predict development of celiac disease. Microbiome. 2018;6(1):36.
23. See JA, Kaukinen K, Makharia GK, Gibson PR, Murray JA. Practical insights into gluten-free diets. Nat Rev Gastroenterol Hepatol. 2015;12(10):580-91.
24. Bascunan KA, Vespa MC, Araya M. Celiac disease: understanding the gluten-free diet. Eur J Nutr. 2017;56(2):449-59.
25. Melini V, Melini F. Gluten-Free Diet: Gaps and needs for a healthier diet. Nutrients. 2019;11(1):170.
26. Di Nardo G, Villa MP, Conti L, Ranucci G, Pacchiarotti C, Principessa L, et al. Nutritional deficiencies in children with celiac disease resulting from a gluten-free diet: A systematic review. Nutrients. 2019;11(7).
27. Simpson HL, Campbell BJ. Dietary fibre–microbiota interactions. Aliment Pharmacol Ther. 2015;42(2):158- 79.
28. Scott KP, Gratz SW, Sheridan PO, Flint HJ, Duncan SH. The influence of diet on the gut microbiota. Pharmacol Res. 2013;69(1):52-60.
29. Sanz Y. Microbiome and gluten. Ann Nutr Metab. 2015;67(Suppl. 2):27-42.
30. Bonder MJ, Tigchelaar EF, Cai X, Trynka G, Cenit MC, Hrdlickova B, et al. The influence of a short-term glutenfree diet on the human gut microbiome. Genome Med. 2016;8(1):45.
31. Sanz Y. Effects of a gluten-free diet on gut microbiota and immune function in healthy adult humans. Gut Microbes. 2010;1(3):135-7.
32. Hansen LB, Roager HM, Søndertoft NB, Gøbel RJ, Kristensen M, Vallès-Colomer M, et al. A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults. Nat Commun. 2018;9(1):4630.
33. Drabinska N, Jarocka-Cyrta E, Markiewicz LH, Krupa- Kozak U. The effect of oligofructose-enriched inulin on faecal bacterial counts and microbiota-associated characteristics in celiac disease children following a gluten-free diet: Results of a randomized, placebocontrolled trial. Nutrients. 2018;10(2).
34. Leinonen H, Kivela L, Lahdeaho ML, Huhtala H, Kaukinen K, Kurppa K. Daily life restrictions are common and associated with health concerns and dietary challenges in adult celiac disease patients diagnosed in childhood. Nutrients. 2019;11(8).
35. Imran Aziz, Kate E Evans, Vasiliki Papageorgiou, Sanders DS. Are patients with coeliac disease seeking alternative therapies to a gluten-free diet? J Gastrointestin Liver Dis. 2011;20(1):27-31.
36. Olivares M, Castillejo G, Varea V, Sanz Y. 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(1):30-40.
37. Klemenak M, Dolinšek J, Langerholc T, Di Gioia D, Mičetić-Turk D. Administration of Bifidobacterium breve decreases the production of TNF-α in children with celiac disease. Dig Dis Sci. 2015;60(11):3386-92.
38. Quagliariello A, Aloisio I, Bozzi Cionci N, Luiselli D, D’Auria G, Martinez-Priego L, et al. Effect of Bifidobacterium breve on the intestinal microbiota of coeliac children on a gluten free diet: a pilot study. Nutrients. 2016;8(10):660.
39. Primec M, Klemenak M, Di Gioia D, Aloisio I, Cionci NB, Quagliariello A, et al. Clinical intervention using Bifidobacterium strains in celiac disease children reveals novel microbial modulators of TNF-α and shortchain fatty acids. Clin Nutr. 2019;38(3):1373-81.
40. Golfeyz S. Celiac disease and fecal microbiota transplantation: A new beginning? Am J Gastroenterol. 2018;113(8):1256.