Gut microbiota of children with atopic dermatitis: Controlled study in the metropolitan region of São Paulo, Brazil

Main Article Content

Lígia Cristina Fonseca Lahoz Melli
Mírian Silva do Carmo-Rodrigues
Humberto Bezerra Araújo-Filho
Carolina Santos Mello
Soraia Tahan
Antônio Carlos Campos Pignatari
Dirceu Solé
Mauro Batista de Morais

Keywords

Children, Microbiota, Colon, Atopic dermatitis

Abstract

Background: It is possible that imbalances in the composition of the gut microbiota or the relationship ofthe microbiota with the host may be implicated in the origin of allergy. Therefore, we studied the intestinal microbiota of children with atopic dermatitis (AD).


Methods: Cross-sectional study with 81 children aged 5---11; 23 with AD and 58 controls. Surveys were conducted to obtain demographic, socioeconomic and neonatal data. Diagnosis of AD was made based on the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Eubacteria, Bacteroidetes, Firmicutes, B. fragilis, E. coli, Lactobacillus spp., S. aureus, E. faecalis, Salmonella spp., M. smithii, Bifidobacterium spp., C. difficile and C. perfringens were quantified using real-time PCR.


Results: The analysis showed an association between presence of C. difficile (OR: 5.88; 95 % CI: 1.24; 27.98), greater abundance of bifidobacteria (OR: 11.09; 95 % CI: 2.14; 57.39) and a lower abundance of lactobacilli (OR: 0.07; 95 % CI: 0.01; 0.51) in the gut microbiota of children with AD. Counts of Eubacteria (0,05 × 103 and 8.49 × 103), B. fragilis (0.72 × 109 and 4.5 × 109), Lactobacillus spp. (0.02 × 108 and 0.38 × 108), E. coli (0.13 × 109 and 1.52 × 109) and M. smithii (0.02 × 108 and 0.31 × 108) were lower in children with AD (P < 0.05).


Conclusions: This study confirmed that children living in the metropolitan area of São Paulo (Brazil) with AD have a different microbiota pattern with higher prevalence of C. difficile, lower abundance of Lactobacillus and greater abundance of bifidobacteria, regardless of socioeconomic status.

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References

1. Carson CG. Risk factors for developing atopic dermatitis. Dan Med J. 2013;60(7): B4687.

2. Solé D, Wandalsen GF, Camelo-Nunes IC, Naspitz CK, ISAAC - GrupoBrasileiro. Prevalence of symptoms of asthma, rhinitis, and atopic eczema among Brazilian children and adolescents identified by the International Study of Asthma and Allergies in Childhood (ISAAC) - Phase 3. J Pediatr (Rio J). 2006;82: 341-6.

3. Ben-Gashir MA. Relationship between quality of life and disease severity in atopic dermatitis/eczema syndrome during childhood. Curr Opin Allergy Clin Immunol. 2003;3(5): 369-73.

4. Sybilski AJ, Raciborski F, Lipiec A, Tomaszewska A, Lusawa A, Samel-Kowalik P, et al. B. Epidemiology of atopic dermatitis in Poland according to the Epidemiology of Allergic Disorders in Poland (ECAP) study. J Dermatol. 2015;42(2): 140-7.

5. Draaisma E, Garcia-Marco L, Mallol J, Solé D, Pérez-Fernandez V, Brand PLP, et al. A multinational study to compare prevalence of atopic dermatitis in the first year of life. Pediatr Allergy Immunol. 2015;26(4):359-66.

6. Kalliomäki M, Kirjavainen P, Eerola E, Kero P, Salminen S, Isolauri E. Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing. J Allergy Clin Immunol. 2001;107:129-34.

7. Rautava S, Ruuskanen O, Ouwehand A, Salminen S, Isolauri E. The hygiene hypoteses of atopic disease -an extended version. J Pediatr Gastroenterol Nutr. 2004;38(4):378-88.

8. Melli LCFL, Carmo-Rodrigues MS, Araújo-Filho HB, Solé D, de Morais MB. Intestinal microbiota and allergic diseases: a systematic review. Allergo Immunopathol (Madr). 2016; 44(2):177-88.

9. Sepp E, Julge K, Mikelsaar M, Bjorksten B. Intestinal microbiota and immunoglobulin E responses in 5-year old Estonian children. Clin Exp Allergy. 2005;35:1141-6.

10. Stsepetova J, Sepp E, Julge K, Vaughan E, Mikelsaar M, de Vos WM. Molecularly assessed shifts of Bifidobacterium ssp. and less diverse microbial communities are characteristic of 5-year-old allergic children. FEMS Immunol Med Microbiol. 2007;51:260-9.

11. Solé D, Vanna AT, Yamada E, Rizzo MCV, Naspitz CK. International Study on Asthma and Allergies in Children (ISAAC) written questionnaire: validation of the asthma component among Brazilian children. Invest Allergol Clin Immunol. 1998;8:376-82.

12. Mello CS, Rodrigues MS, Filho HB, Melli LC, Tahan S, Pignatari AC, et al. Fecal microbiota analysis of children with small intestinal bacterial overgrowth among residents of an urban slum in Brazil. J Pediatr (Rio J). 2018;94:483-90.

13. Verma R, Verma AK, Ahuja V, Paul J. Real-time analysis of mucosal flora in patients with inflammatory bowel disease in India. J Clin Microbiol. 2010;48(11):4279-82.

14. Bjorksten B, Sepp E, Julge K, Voor T, Mikelsaar M. Allergy development and the intestinal microflora during the first year of
life. J Allergy Clin Immunol. 2001;108:516-20.

15. Penders J, Stobberinghw EE, Thijs C, Adamsw H, Vinkw C, van Ree R, van den Brandt PA. Molecular fingerprinting of the intestinal microbiota of infants in whom atopic eczema was or was not developing. Clin Exp Allergy. 2006;36:1602-8.

16. Penders J, Thijs C, van den Brandt PA, Kummeling I, Snijders B, Stelma F, et al. Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study. Gut. 2007;56:661-7.

17. Nylund L, Satokari R, Nikkilä J, Rajili´c-Stojanovi´c M, Kalliomäki M, Isolauri E, et al. Microarray analysis reveals marked intestinal microbiota aberrancy in infants having eczema compared to healthy children in at-risk for atopic disease. BMC Microbiol. 2013;13:12.

18. Zhang G, Svenungsson B, Kamell A, Weintraub A. Prevalence of enterotoxigenic bacteróides fragilis in adult patients with diarrhea and healthy controls. Clin Infec Dis. 1999;29(3): 590-4.

19. Freeman J, Wilcox MH. Antibiotics and Clostridium difficile. Microbes infec. 1999;1(5):377-84.

20. Storro Ø, Øien T, Langsrud Ø, Rudi K, Dotterud C, Johnsen R. Temporal variations in early gut microbial colonization are associated with allergen-specific immunoglobulin E but not atopic eczema at 2 years of age. Clin Exp Allergy. 2011;41: 1545-54.

21. Johansson MA, Sjögren IM, Persson JO, Nilsson C, SverremarkEkstro E. Early colonization with a group of lactobacilli decreases the risk for allergy at five years of age despite allergic heredity. PLoS One. 2011;6(8):e23031.

22. Penders J, Thijs C, Mommers M, Stobberingh EE, Dompeling E, Reijmerink NE, et al. Intestinal lactobacilli and the DC-SIGN gene for their recognition by dendritic cells play a role in the aetiology of allergic manifestations. Microbiology. 2010;156:3298-305.

23. Sjögren YM, Jenmalmw MC, Böttcherw MF, Björksténz B, Sverremark-Ekström E. Altered early infant gut microbiota in children developing allergy up to 5 years of age. Clin Exp Allergy. 2009;39:518-26.

24. Morais MB, Jacob CM. The role of probiotics and prebiotics in pediatric practice. J Pediatr. 2006;82:S189-97.

25. Watanabe S, Narisawa Y, Arase S, Okamatsu H, Ikenaga T, Tajiri Y, et al. Differences in fecal microflora between patients with atopic dermatitis and healthy control subjects. J Allergy Clin Immunol. 2003;111:587-91.

26. Sepp E, Julge K, Mikelsaar M, Bjorktén B. Intestinalmicrobiota and immunoglobulin E responses in 5-year-old Estonian Children. Clin Exp Allergy. 2005;35:1141-6.

27. Candela M, Rampelli S, Turroni S, Severgnini M, Consolandi C, De Bellis G, et al. Unbalance of intestinal microbiota in atopic children. BMC Microbiol. 2012;12:95.

28. Vael C, Nelen V, Verhulst SL, Goossens H, Desager KN. Early intestinal Bacteroides fragilis colonisation and development of asthma. BMC Pulm Med. 2008;8:19.

29. Vael C, Vanheirstraeten L, Desager KN, Goossens H. Denaturing gradient gel electrophoresis of neonatal intestinal microbiota in relation to the development of asthma. Microbiology. 2011;11:68.

30. Kirjavainen PV, Apostolou E, Arvola T, Salminen SJ, Gibson GR, Isolauri E. Characterizing the composition of intestinal microflora as a prospective treatment target in infant allergic disease. FEMS Immunol Med Microbiol. 2001;32: 1-7.

31. Avershina E, Storrø O, Øien T, Johnsen R, Pope P, Rudi K. Major faecal microbiota shifts in composition and diversity with age in a geographically restricted cohort of mothers and their children. FEMS Microbiol Ecol. 2014;87:280-90.

32. Horz HP, Conrads G. The discussion goes on: what is the role of euryarchaeota in humans? Archea. 2010:8. Article ID 967271.

33. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, et al. Diversity of the human intestinal microbial flora.
Science. 2005;308:1635-8.

34. Storrø O, Avershinab E, Rudi K. Diversity of intestinal microbiota in infancy and the risk of allergic disease in childhood. Curr Opin
Allergy Clin Immunol. 2013;13:257-62.

35. Vael C, Desager K. The importance of the development of the intestinal microbiota in infancy. Curr Opin Pediatr. 2009;21:794-800.

36. Forastiere F, Agabiti N, Corbo GM, Dell’Orco V, Porta D, Pistelli R, et al. Socioeconomic status, number of siblings, and respiratory infections in early life as determinants of atopy in children. Epidemiology. 1997;8(5):566-70.

37. Ismail IH, Oppedisano F, Joseph SJ, Boyle RJ, Licciardi PV, Robins-Browne RM, et al. Reduced gut microbial diversity in early life is associated with later development of eczema but not atopy in high-risk infants. Paediatr Allergy Immunol. 2012;23:674-81.

38. Gustafsson D, Sjöberg O, Foucard T. Development of allergies and asthma in infants and young children with atopic dermatitis - a prospective follow-up to 7 years of age. Allergy. 2000;55:240-5.

39. Van Der Hulst AE, Klip H, Brand PL. Risk of developing asthma in young children with atopic eczema: a systematic review. J Allergy Clin Immunol. 2007;120(3):565-9.