The role of gut microbiota and vitamin D in the development of atopic dermatitis and food allergies in children

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Abstract

BACKGROUND: Gut microbiota and vitamin D may be instrumental in the development of atopic responses (atopic dermatitis, allergic rhinitis, allergic asthma, and food allergies) in children. Various diseases or immune pathologies, in particular atopic dermatitis and food allergies, are among manifestations of an imbalance in the composition of gut microorganisms. On top of that, vitamin D is a significant contributor both to modulating the gut microbiome composition and to diverse immune responses from innate and adaptive immunity, which affords ground for studying the relationship between these aspects in the context of the development of atopic conditions. So far, the relationship between the gut microbiota, vitamin D, and the development of these conditions in children has not been sufficiently explored.

AIM: To study the relationship between the gut microbiota imbalance and immune disorders, in particular the development of food allergies and atopic dermatitis in children; to identify the relationship between bacterial signatures and vitamin D concentrations in children with atopic dermatitis and food allergies.

METHODS: The 16S ribosomal ribonucleic acid gene of 150 fecal samples from children aged 3 to 12 years was sequenced. The concentration of vitamin D in the participants’ blood serum was determined using enzyme-linked immunosorbent assay. Thereafter, the relationship between certain bacterial signatures and serum 25(OH)D concentration was characterized through the use of statistical models (regression tree, correlation analysis, and linear regression).

RESULTS: In all mathematical models used, vitamin D concentration turned out to be associated with bacterial families important for atopy, such as Lachnospiraceae, Ruminococcaceae, and Sutterellaceae. The results showed that dysbiosis coupled with vitamin D deficiency is typical of the atopic profile, which may indicate the influence of these conditions on the immune system imbalance toward the Th2 response and, consequently, on the development of allergic conditions.

CONCLUSION: Certain bacterial patterns specific to atopy are associated with vitamin D concentration in blood serum. In consequence of the study, we concluded that the gut microbiota and vitamin D may be systematically involved in modulating immune responses. Further research is needed to attain full comprehension of the mechanisms underlying these associations and to determine the most efficient interventions for the prevention and treatment of autoimmune conditions.

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About the authors

Irina G. Kalashnikova

Centre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical and Biological Agency

Author for correspondence.
Email: igkalashnikova@cspfmba.ru
ORCID iD: 0009-0003-8764-3286
SPIN-code: 4203-1495

MD

Russian Federation, bldg 1, 10 Pogodinskaja st, Moscow, 119121

Alexsandra I. Nekrasova

Centre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical and Biological Agency

Email: akinshina@cspfmba.ru
ORCID iD: 0000-0002-7951-2003
SPIN-code: 8168-0163

MD

Russian Federation, bldg 1, 10 Pogodinskaja st, Moscow, 119121

Anna V. Korobeinikova

Centre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical and Biological Agency

Email: akorobeinikova@cspfmba.ru
ORCID iD: 0009-0003-0556-9343
SPIN-code: 7221-8903
Russian Federation, bldg 1, 10 Pogodinskaja st, Moscow, 119121

Angelica V. Zagainova

Centre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical and Biological Agency

Email: azagaynova@cspmz.ru
ORCID iD: 0000-0003-4772-9686
SPIN-code: 6642-7819

Cand. Sci. (Biology)

Russian Federation, bldg 1, 10 Pogodinskaja st, Moscow, 119121

Natalia V. Lavrushkina

Email: nlavrushkina@cspfmba.ru
ORCID iD: 0009-0007-2831-0712

Vladimir S. Yudin

Centre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical and Biological Agency

Email: vyudin@cspfmba.ru
ORCID iD: 0000-0002-9199-6258
SPIN-code: 7592-9020

Cand. Sci. (Biology)

Russian Federation, bldg 1, 10 Pogodinskaja st, Moscow, 119121

Valentin V. Makarov

Centre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical and Biological Agency

Email: makarov@cspfmba.ru
ORCID iD: 0000-0001-9495-0266
SPIN-code: 7842-8808

Cand. Sci. (Biology)

Russian Federation, bldg 1, 10 Pogodinskaja st, Moscow, 119121

Anton A. Keskinov

Centre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical and Biological Agency

Email: keskinov@cspfmba.ru
ORCID iD: 0000-0001-7378-983X
SPIN-code: 7178-5020

MD, Cand. Sci. (Medicine)

Russian Federation, bldg 1, 10 Pogodinskaja st, Moscow, 119121

Sergey M. Yudin

Centre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical and Biological Agency

Email: yudin@cspmz.ru
ORCID iD: 0000-0002-7942-8004
SPIN-code: 9706-5936

MD, Dr. Sci. (Medicine), Professor

Russian Federation, bldg 1, 10 Pogodinskaja st, Moscow, 119121

References

  1. Dierick BJH, van der Molen T, Flokstra-de Blok BMJ, et al. Burden and socioeconomics of asthma, allergic rhinitis, atopic dermatitis and food allergy. Expert Rev Pharmacoecon Outcomes Res. 2020;20(5):437–453. doi: 10.1080/14737167.2020.1819793 EDN: KIXEKK
  2. Platts-Mills TA. The allergy epidemics: 1870–2010. J Allergy Clin Immunol. 2015;136(1):3–13. doi: 10.1016/j.jaci.2015.03.048
  3. Sokolova T, Davidenko M. Statistics of prevalence and sickness rate at atopic dermatitis of children and teenagers: pro and contra. Immunopathology, Allergology, Infectology. 2019;(1):80–88. doi: 10.14427/jipai.2019.1.80 EDN: OTLJUN
  4. Cait A, Cardenas E, Dimitriu PA, et al. Reduced genetic potential for butyrate fermentation in the gut microbiome of infants who develop allergic sensitization. J Allergy Clin Immunol. 2019;144(6):1638–1647.e3. doi: 10.1016/j.jaci.2019.06.029
  5. Chun J, Lee SM, Ahn YM, et al. Modulation of the gut microbiota by sihocheonggan-tang shapes the immune responses of atopic dermatitis. Front Pharmacol. 2021;12:722730. doi: 10.3389/fphar.2021.722730 EDN: HZQNKQ
  6. Huang YJ, Marsland BJ, Bunyavanich S, et al. The microbiome in allergic disease: Current understanding and future opportunities-2017 PRACTALL document of the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergy and Clinical Immunology. J Allergy Clin Immunol. 2017;139(4):1099–1110. doi: 10.1016/j.jaci.2017.02.007
  7. Kalashnikova IG, Nekrasova AI, Korobeynikova AV, et al. The association between gut microbiota and serum biomarkers in children with atopic dermatitis. Biomedicines. 2024;12(10):2351. doi: 10.3390/biomedicines12102351 EDN: PPIJYN
  8. Murdaca G, Gerosa A, Paladin F, et al. Vitamin D and microbiota: is there a link with allergies? Int J Mol Sci. 2021;22(8):4288. doi: 10.3390/ijms22084288 EDN: ZRMEEX
  9. Hooper LV, Littman DR, Macpherson AJ. Interactions between the microbiota and the immune system. Science. 2012;336(6086):1268–1273. doi: 10.1126/science.1223490
  10. Maiello N, Comberiati P, Giannetti A, et al. New directions in understanding atopic march starting from atopic dermatitis. Children (Basel). 2022;9(4):450. doi: 10.3390/children9040450 EDN: UWNZAU
  11. Peroni DG, Nuzzi G, Trambusti I, et al. Microbiome composition and its impact on the development of allergic diseases. Front Immunol. 2020;11:700. doi: 10.3389/fimmu.2020.00700 EDN: XYUYDM
  12. Nekrasova AI, Kalashnikova IG, Bobrova MM, et al. Characteristics of the gut microbiota in regard to atopic dermatitis and food allergies of children. Biomedicines. 2024;12(3):553. doi: 10.3390/biomedicines12030553 EDN: JJYQKW
  13. Camargo CA Jr, Ganmaa D, Sidbury R, et al. Randomized trial of vitamin D supplementation for winter-related atopic dermatitis in children. J Allergy Clin Immunol. 2014;134(4):831–835.e1. doi: 10.1016/j.jaci.2014.08.002
  14. Sidbury R, Sullivan AF, Thadhani RI, Camargo CA Jr. Randomized controlled trial of vitamin D supplementation for winter-related atopic dermatitis in Boston: a pilot study. Br J Dermatol. 2008;159(1):245–247. doi: 10.1111/j.1365-2133.2008.08601.x
  15. Yamamoto EA, Jørgensen TN. Relationships between vitamin D, gut microbiome, and systemic autoimmunity. Front Immunol. 2020;10:3141. doi: 10.3389/fimmu.2019.03141 EDN: FCFOSI
  16. 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
  17. West CE, Rydén P, Lundin D, et al. Gut microbiome and innate immune response patterns in IgE-associated eczema. Clin Exp Allergy. 2015;45(9):1419–1429. doi: 10.1111/cea.12566
  18. Ali A, Wu L, Ali SS. Vitamin D and the microbiota connection: understanding its potential to improve COPD outcomes. Egyptian Journal of Bronchology. 2024;18(1):20. doi: 10.1186/s43168-024-00271-4 EDN: INJIHH
  19. Berni Canani R, Paparo L, Nocerino R, et al. Gut microbiome as target for innovative strategies against food allergy. Front Immunol. 2019;10:191. doi: 10.3389/fimmu.2019.00191
  20. Rooks MG, Garrett WS. Gut microbiota, metabolites and host immunity. Nat Rev Immunol. 2016;16(6):341–352. doi: 10.1038/nri.2016.42
  21. Bozzetto S, Carraro S, Giordano G, et al. Asthma, allergy and respiratory infections: the vitamin D hypothesis. Allergy. 2012;67(1):10–17. doi: 10.1111/j.1398-9995.2011.02711.x
  22. Clark A, Mach N. Role of vitamin D in the hygiene hypothesis: the interplay between vitamin D, vitamin D receptors, gut microbiota, and immune response. Front Immunol. 2016;7:627. doi: 10.3389/fimmu.2016.00627 EDN: YXMDDJ
  23. Ginde AA, Liu MC, Camargo CA Jr. Demographic differences and trends of vitamin D insufficiency in the US population, 1988–2004. Arch Intern Med. 2009;169(6):626–632. doi: 10.1001/archinternmed.2008.604
  24. Mullins RJ, Camargo CA. Latitude, sunlight, vitamin D, and childhood food allergy/anaphylaxis. Curr Allergy Asthma Rep. 2012;12(1):64–71. doi: 10.1007/s11882-011-0230-7 EDN: YCJMVC
  25. Rudders SA, Camargo CA Jr. Sunlight, vitamin D and food allergy. Curr Opin Allergy Clin Immunol. 2015;15(4):350–357. doi: 10.1097/ACI.0000000000000177
  26. Osborne NJ, Ukoumunne OC, Wake M, Allen KJ. Prevalence of eczema and food allergy is associated with latitude in Australia. J Allergy Clin Immunol. 2012;129(3):865–867. doi: 10.1016/j.jaci.2012.01.037
  27. Matsui T, Tanaka K, Yamashita H, et al. Food allergy is linked to season of birth, sun exposure, and vitamin D deficiency. Allergol Int. 2019;68(2):172–177. doi: 10.1016/j.alit.2018.12.003
  28. Hollams EM, Hart PH, Holt BJ, et al. Vitamin D and atopy and asthma phenotypes in children: a longitudinal cohort study. Eur Respir J. 2011;38(6):1320–1327. doi: 10.1183/09031936.00029011
  29. Akimbekov NS, Digel I, Sherelkhan DK, et al. Vitamin D and the host-gut microbiome: a brief overview. Acta Histochem Cytochem. 2020;53(3):33–42. doi: 10.1267/ahc.20011 EDN: OEZVRK
  30. Kim MJ, Kim SN, Lee YW, et al. Vitamin D status and efficacy of vitamin D supplementation in atopic dermatitis: a systematic review and meta-analysis. Nutrients. 2016;8(12):789. doi: 10.3390/nu8120789
  31. Allen KJ, Koplin JJ, Ponsonby AL, et al. Vitamin D insufficiency is associated with challenge-proven food allergy in infants. J Allergy Clin Immunol. 2013;131(4):1109–1116.e11166. doi: 10.1016/j.jaci.2013.01.017
  32. Wjst M. The vitamin D slant on allergy. Pediatr Allergy Immunol. 2006;17(7):477–483. doi: 10.1111/j.1399-3038.2006.00456.x
  33. Weisse K, Winkler S, Hirche F, et al. Maternal and newborn vitamin D status and its impact on food allergy development in the German LINA cohort study. Allergy. 2013;68(2):220–228. doi: 10.1111/all.12081
  34. Khoo AL, Chai LY, Koenen HJ, et al. Regulation of cytokine responses by seasonality of vitamin D status in healthy individuals. Clin Exp Immunol. 2011;164(1):72–79. doi: 10.1111/j.1365-2249.2010.04315.x
  35. Vasiliou JE, Lui S, Walker SA, et al. Vitamin D deficiency induces Th2 skewing and eosinophilia in neonatal allergic airways disease. Allergy. 2014;69(10):1380–1389. doi: 10.1111/all.12465
  36. Li Q, Zhou Q, Zhang G, et al. Vitamin D supplementation and allergic diseases during childhood: a systematic review and meta-analysis. Nutrients. 2022;14(19):3947. doi: 10.3390/nu14193947 EDN: VSFODV
  37. Wjst M. Is vitamin D supplementation responsible for the allergy pandemic?. Curr Opin Allergy Clin Immunol. 2012;12(3):257–262. doi: 10.1097/ACI.0b013e3283535833
  38. Aranow C. Vitamin D and the immune system. J Investig Med. 2011;59(6):881–886. doi: 10.2310/JIM.0b013e31821b8755
  39. Weiss ST, Litonjua AA. Vitamin D, the gut microbiome, and the hygiene hypothesis. How does asthma begin?. Am J Respir Crit Care Med. 2015;191(5):492–493. doi: 10.1164/rccm.201501-0117ED
  40. Litonjua AA, Weiss ST. Is vitamin D deficiency to blame for the asthma epidemic? J Allergy Clin Immunol. 2007;120(5):1031–1035. doi: 10.1016/j.jaci.2007.08.028
  41. Forno E, Onderdonk AB, McCracken J, et al. Diversity of the gut microbiota and eczema in early life. Clin Mol Allergy. 2008;6:11. doi: 10.1186/1476-7961-6-11 EDN: MUDNZR
  42. Zosky GR, Berry LJ, Elliot JG, et al. Vitamin D deficiency causes deficits in lung function and alters lung structure. Am J Respir Crit Care Med. 2011;183(10):1336–1343. doi: 10.1164/rccm.201010-1596OC
  43. Gromova OA, Torshin IYu, Zakharova IN, et al. Vitamin D defi ciency and comorbid conditions in children 7-16 years of age: intelligent data analysis. Good Clinical Practice. 2017;(4):58–67. doi: 10.24411/2588-0519-2017-00031 EDN: YOSRPZ
  44. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2024;109(10):e1991. doi: 10.1210/clinem/dgae373 Erratum for: J Clin Endocrinol Metab. 2011;96(7):1911–1930. doi: 10.1210/jc.2011-0385
  45. Odinaeva ND, Kondratyeva EI, Loshkova EV, et al. Seasonal variations in serum vitamin D levels in children and adults with various diseases. Pediatric Nutrition. 2022;20(2):29–37. doi: 10.20953/1727-5784-2022-2-29-37 EDN: TFNYIG
  46. Maltsev SV, Zakirova AM, Mansurova GSh. Vitamin D provision in children of different age groups during the winter season. Russian Bulletin of Perinatology and Pediatrics. 2017;62:(2):99–103. doi: 10.21508/1027-4065-2017-62-2-99-103 EDN: YOCWRF
  47. Zakharova IN, Tvorogova TM, Solovjeva EA, et al. Insufficiency of vitamin D in children in the city of Moscow depending on the year season. Prakticheskaja medicina. 2017;(5):28–31.
  48. Prescott J. The Emerging role of the type 2 inflammatory cascade in atopic diseases. Am J Manag Care. 2019;4–8.
  49. Ngoc PL, Gold DR, Tzianabos AO, et al. Cytokines, allergy, and asthma. Curr Opin Allergy Clin Immunol. 2005;5(2):161–166. doi: 10.1097/01.all.0000162309.97480.45
  50. Beane KE, Redding MC, Wang X, et al. Effects of dietary fibers, micronutrients, and phytonutrients on gut microbiome: a review. Appl Biol Chem. 2021;64:36. doi: 10.1186/s13765-021-00605-6
  51. Battistini C, Ballan R, Herkenhoff ME, et al. Vitamin D modulates intestinal microbiota in inflammatory Bowel diseases. Int J Mol Sci. 2020;22(1):362. doi: 10.3390/ijms22010362 EDN: JHLWGK
  52. Ooi JH, Li Y, Rogers CJ, Cantorna MT. Vitamin D regulates the gut microbiome and protects mice from dextran sodium sulfate-induced colitis. J Nutr. 2013;143(10):1679–1686. doi: 10.3945/jn.113.180794
  53. Jin D, Wu S, Zhang YG, et al. Lack of vitamin D receptor causes dysbiosis and changes the functions of the murine intestinal microbiome. Clin Ther. 2015;37(5):996–1009.e7. doi: 10.1016/j.clinthera.2015.04.004
  54. Nekrasova AI, Kalashnikova IG, Petryaykina ES, et al. The effect of vitamins and micronutrients on the intestinal microbiota in norm and pathology. Russian Medicine. 2025;31(1):51–60. doi: 10.17816/medjrf634521 EDN: AHPHPU
  55. Tangestani H, Boroujeni HK, Djafarian K, et al. Vitamin D and the gut microbiota: a narrative literature review. Clin Nutr Res. 2021;10(3):181–191. doi: 10.7762/cnr.2021.10.3.181 EDN: BUUZQN
  56. Tabassum A, Ali A, Zahedi FD, Ismail NAS. Immunomodulatory role of vitamin D on gut microbiome in children. Biomedicines. 2023;11(5):1441. doi: 10.3390/biomedicines11051441 EDN: PVQHKX
  57. Bellerba F, Muzio V, Gnagnarella P, et al. The association between vitamin D and gut microbiota: a systematic review of human studies. Nutrients. 2021;13(10):3378. doi: 10.3390/nu13103378 EDN: QIYHEK
  58. Luthold RV, Fernandes GR, Franco-de-Moraes AC, et al. Gut microbiota interactions with the immunomodulatory role of vitamin D in normal individuals. Metabolism. 2017;69:76–86. doi: 10.1016/j.metabol.2017.01.007
  59. Kwek E, Yan C, Ding H, et al. Effects of hawthorn seed oil on plasma cholesterol and gut microbiota. Nutr Metab (Lond). 2022;19(1):55. doi: 10.1186/s12986-022-00690-4 EDN: BRTPEZ
  60. Wu S, Zhang YG, Lu R, et al. Intestinal epithelial vitamin D receptor deletion leads to defective autophagy in colitis. Gut. 2015;64(7):1082–1094. doi: 10.1136/gutjnl-2014-307436
  61. Wang J, Thingholm LB, Skiecevičienė J, et al. Genome-wide association analysis identifies variation in vitamin D receptor and other host factors influencing the gut microbiota. Nat Genet. 2016;48(11):1396–1406. doi: 10.1038/ng.3695
  62. Shang M, Sun J. Vitamin D/VDR, probiotics, and gastrointestinal diseases. Curr Med Chem. 2017;24(9):876–887. doi: 10.2174/0929867323666161202150008
  63. Szaleniec M, Wojtkiewicz AM, Bernhardt R, et al. Bacterial steroid hydroxylases: enzyme classes, their functions and comparison of their catalytic mechanisms. Appl Microbiol Biotechnol. 2018;102(19):8153–8171. doi: 10.1007/s00253-018-9239-3 EDN: YCFCAX
  64. Jones ML, Martoni CJ, Prakash S. Oral supplementation with probiotic L. reuteri NCIMB 30242 increases mean circulating 25-hydroxyvitamin D: a post hoc analysis of a randomized controlled trial. J Clin Endocrinol Metab. 2013;98(7):2944–2951. doi: 10.1210/jc.2012-4262 EDN: YDRXVL
  65. Naderpoor N, Mousa A, Fernanda Gomez Arango L, et al. Effect of vitamin D supplementation on faecal microbiota: a randomised clinical trial. Nutrients. 2019;11(12):2888. doi: 10.3390/nu11122888 EDN: NUMHXH

Supplementary files

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2. Fig. 1. Effect of vitamin D concentration on intestinal microbiota and development of atopy. IL — interleukin.

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3. Fig. 2. Study participants.

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4. Fig. 3. Concentration of vitamin D in the serum of participants by groups: a — frequency distribution of 25(OH)D concentration in participants; b — 25(OH)D concentration by groups; × — sample mean.

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5. Fig. 4. Regression tree for vitamin D as an independent variable. Ribosomal databases: a — RDP, b — SILVA. Tree nodes correspond to the threshold values of variables for classification into groups. The concentration of 25(OH)D is given in ng/ml, n is the minimum number of patients for the specified threshold, respectively. Tree branches correspond to the number of taxon representatives for the group, p < 0.05.

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СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
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