Changes in Intestinal Microbiota Composition in 1–5 Years Old Children with Atopic Dermatitis: Cross Sectional Study

Background. Atopic dermatitis (AD) arouses high research interest these days due to its significant morbidity rate. The most crucial risk factor for its development is the intestinal microbiota composition. The correlation of this factor with the development of AD in children requires further study.

Objective. The aim of the study is to perform comparative analysis of the intestinal microbiota in 1–5 years old children with AD and conditionally healthy children via 16S-sequencing of ribosomal RNA (rRNA) of bacterial genes.

Methods. We have conducted cross sectional study. 60 children with diagnosed AD and 15 conditionally healthy children aged from 1 to 5 years were surveyed. Intestinal microbiota was examined via 16S-sequencing of rRNA of bacterial genes.

Results. The intestinal microbiota in children with AD and conditionally healthy children has statistically significant differences. Despite the absence of significant differences in species richness of compared groups, children with AD had the elevation in the metagenome of Proteobacteria; Bacilli and Gammaproteobacteria classes; Enterococcaceae and Veillonellaceae families; Eggerthella, Dialister and Enterobacter genus; as well as the decrease in the relative value of Actinobacteria, Bacteroidetes, Verrucomicrobia; Bacteroidales and Bifidobacteriales orders; Bifidobacteriaceae, Bacteroidaceae, Erysipelotrichaceae families; Lachnoclostridium, Roseburia, Prevotella, Coprococcus, Ruminococcus, Faecalibacterium, Bifidobacterium, Bacteroides genus; decrease of Bifidobacterium longum, Faecalibacterium prausnitzii, Bacteroides fragilis.

Conclusion. It was revealed that the intestinal microbiota of children with AD has significant differences in taxonomic composition with the microbiota of conditionally healthy children. Elevation of Proteobacteria, Bacilli and Gammaproteobacteria classes, Eggerthella, Dialister and Enterobacter genus can be the risk factor for this disease development, whereas decrease of such bacteria as Verrucomicrobia, Bacteroidales and Bifidobacteriales can aggravate atopic symptoms. Thus, the need for further study of intestinal microbiota in children with AD is justified to establish the correlation of these bacteria with the disease course. 

1. Penders J, Gerhold K, Stobberingh EE, et al. Establishment of the intestinal microbiota and its role for atopic dermatitis in early childhood. J Allergy Clin Immunol. 2013;132(3):601–607.e8. doi: 10.1016/j.jaci.2013.05.043

2. Nikolaeva I.V., Tsaregorodtsev AD, Shaikhieva G S. Formation of intestinal microbi- ota of children and the factors that influence this process. Rossijskij vestnik perinatologii i pediatrii. 2018;63(3):13–18. (In Russ). doi: 10.21508/1027-4065-2018-63-3-13-18

3. Mazankova LN, Zaharova IN, Dmitrieva JA. Conceptual approach to administrate probiotics-synbiotics in children. Detskie infekcii = Children Infections. 2010;9(1):27–32. (In Russ).

4. Hesla HM, Stenius F, Jäderlund L, et al. Impact of lifestyle on the gut microbiota of healthy infants and their mothers — the ALADDIN birth cohort. Microbiol Ecol. 2014;90(3):791–801. doi: 10.1111/1574-6941.12434

5. Maksimova OV, Gervazieva VB, Zverev VV. Intestine microbiota and allergic diseases. Zhurnal mikrobiologii, èpidemiologii i immunobiologii = Journal of Microbiology, Epidemiology and Immunobiology. 2014;(3):49–60. (In Russ).

6. Smirnova GI, Mankute GR. Intestinal microbiota and atopic dermatitis in children. Rossiiskii Pediatricheskii Zhurnal = Russian Pediatric Journal. 2015;18(6): 46–53. (In Russ).

7. Song H, Yoo Y, Hwang J, et al. Faecali bacterium prausnitzii subspecies-level dysbiosis in the human gut microbiome underlying atopic dermatitis. J Allergy Clin Immunol. 2016;137(3):852–860. doi: 10.1016/j.jaci.2015.08.021

8. Dong P, Feng J-J, Yan D-Y, et al. Early-life gut microbiome and cow’s milk allergy — a prospective case-control 6-month follow-up study. Saudi J Biol Sci. 2018;25(5):875–880. doi: 10.1016/j.sjbs

9. Hu C, van Meel ER, Medina-Gomez C, et al. A population-based study on associations of stool microbiota with atopic diseases in school-age children. J Allergy Clin Immunol. 2021;148(2):612–620. doi: 10.1016/j.jaci.2021.04.001

10. Marrs T, Jo JH, Perkin MR, et al. Gut microbiota development during infancy: Impact of introducing allergenic foods. J Allergy Clin Immunol. 2021;147(2):613–621.e9. doi: 10.1016/j.jaci.2020.09.042

11. Yudina YV, Aminova AI, Prodeus AP, et al. Features of the gut microbiota of children aged 1–5 years with atopic dermatitis. Pediatric Nutrition. 2021;19(2):5–13. (In Russ). doi: 10.20953/1727-5784-2021-2-5-13

12. Yudina YV, Aminova AI, Prodeus AP, et al. Intestinal microbiota and the “allergic phenotype” in children. Clinical Practice in Pediatrics. 2021;16(3):35–43. (In Russ). doi: 10.20953/1817-7646-2021-2-35-43

13. Hugerth LW, Andersson AF. Analysing Microbial Community Composition through Amplicon Sequencing: From Sampling to Hypothesis Testing. Front Microbiol. 2017;8:1561. doi: 10.3389/fmicb.2017.01561

14. Merkel AYu, Tarnovetskii IYu, Podosokorskaya OA, Toshchakov SV. Analysis of 16S rRNA primer systems for profiling of thermophilic microbial communities. Microbiology. 2019;88(6):671–680.

15. Bolyen E, Rideout JR, Dillon MR, et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat Biotechnol. 2019;37(8):852–857. doi: 10.1038/s41587-019-0209-9. Erratum in: Nat Biotechnol. 2019;37(9):1091. doi: 10.1038/s41587-019-0252-6.

16. Zol’nikova OYu. Mikrobiota kishechnika i dykhatel’nykh putei kak patogeneticheskoe zveno bronkhial’noi astmy. [dissertation]. Moscow; 2020. 209 p. (In Russ).

17. Ho TTB, Groer MW, Kane B, et al. Dichotomous development of the gut microbiome in preterm infants. Microbiome. 2018;6(1):157. doi: 10.1186/s40168-018-0547-8

18. Binda C, Lopetuso LR, Rizzatti G, et al. Actinobacteria: A relevant minority for the maintenance of gut homeostasis. Dig Liver Dis. 2018;50(5):421–428. doi: 10.1016/j.dld.2018.02.012

19. Björkander S, Carvalho-Queiroz C, Hallberg J, et al. Childhood allergy is preceded by an absence of gut lactobacilli species and higher levels of atopy-related plasma chemokines. Clin Exp Immunol. 2020;202(3):288–299. doi: 10.1111/cei.13494

20. Wopereis H, Sim K, Shaw A, et al. Intestinal microbiota in infants at high risk for allergy: Effects of prebiotics and role in eczema development. J Allergy Clin Immunol. 2018;141(4):1334–1342.e5. doi: 10.1016/J.JACI

21. Berni Canani R, De Filippis F, Nocerino R, et al. Gut microbiota composition and butyrate production in children affected by non-IgE-mediated cow’s milk allergy. Sci Rep. 2018;8(1):12500. doi: 10.1038/s41598-018-30428-3

22. Stephen-Victor E, Chatila TA. Regulation of oral immune tolerance by the microbiome in food allergy. Curr Opin Immunol. 2019;60:141–147. doi: 10.1016/j.coi.2019.06.001.

23. Macchione IG, Lopetuso LR, Ianiro G, et al. Akkermansia muciniphila: key player in metabolic and gastrointestinal disorders. Eur Rev Med Pharmacol Sci. 2019;23(18):8075–8083. doi: 10.26355/eurrev_201909_19024

24. Sroka-Oleksiak A, Młodzińska A, Bulanda M, et al. Metagenomic Analysis of Duodenal Microbiota Reveals a Potential Biomarker of Dysbiosis in the Course of Obesity and Type 2 Diabetes: A Pilot Study. J Clin Med. 2020;9(2):369. doi: 10.3390/jcm9020369

25. Furrie E, Macfarlane S, Cummings JH, Macfarlane GT. 2004. Systemic antibodies towards mucosal bacteria in ulcerative colitis and Crohn’s disease differentially activate the innate immune response. Gut. 2004;53(1):91–98. doi: 10.1136/gut.53.1.91

26. Zheng H, Liang H, Wang Y, et al. Altered Gut Microbiota Composition Associated with Eczema in Infants. PLoS One. 2016;11(11):e0166026. doi: 10.1371/journal.pone.0166026

27. Mondot S, Kang S, Furet JP, et al. Highlighting New Phylogenetic Specificities of Crohn’s Disease Microbiota. Inflamm Bowel Dis. 2011;17(1):185–192. doi: 10.1002/ibd.21436

28. Galazzo G, van Best N, Bervoets L, et al. Development of the Microbiota and Associations With Birth Mode, Diet, and Atopic Disorders in a Longitudinal Analysis of Stool Samples, Collected From Infancy Through Early Childhood. Gastroenterology. 2020;158(6):1584–1596. doi: 10.1053/j.gastro.2020.01.024

29. Ferreira-Halder CV, Faria AVS, Andrade SS. Action and function of Faecalibacterium prausnitzii in health and disease. Best Pract Res Clin Gastroenterol. 2017;31(6):643–648. doi: 10.1016/j.bpg.2017.09.011