Filaggrin Mutation Status and Prevention of Atopic Dermatitis with Maternal Probiotic Supplementation
DOI:
https://doi.org/10.2340/actadv.v104.24360Keywords:
atopic dermatitis, child, preschool, filaggrin, gene, probioticAbstract
The World Allergy Organization recommends probiotics in the prevention of atopic dermatitis in high-risk populations. Mutations in the filaggrin gene (FLG) result in an increased risk of atopic dermatitis through disruption of the skin keratin layer. This exploratory study investigated whether the preventive effect of maternal probiotics was evident in children with and without FLG mutations. DNA was collected from children (n = 228) from the Probiotic in the Prevention of Allergy among Children in Trondheim (ProPACT) study. Samples were analysed for 3 common FLG mutations (R501X, R2447X, and 2282del4). Overall, 7% of children had heterozygous FLG mutations; each child had only one of the 3 mutations. Mutation status had no association with atopic dermatitis (RR = 1.1; 95% CI 0.5 to 2.3). The risk ratio (RR) for having atopic dermatitis following maternal probiotics was 0.6 (95% CI 0.4 to 0.9) and RR was similar if the child expressed an FLG mutation (RR = 0.6; 95% CI 0.1 to 4.1) or wildtype FLG (RR = 0.6; 95% CI 0.4 to 0.9). The preventive effect of probiotics for atopic dermatitis was also evident in children without FLG mutation. Larger confirmatory studies are needed.
Downloads
References
McKenna SP, Doward LC, Meads DM, Tennant A, Lawton G, Grueger J. Quality of life in infants and children with atopic dermatitis: addressing issues of differential item functioning across countries in multinational clinical trials. Health Qual Life Outcomes 2007; 5: 45.
https://doi.org/10.1186/1477-7525-5-45 DOI: https://doi.org/10.1186/1477-7525-5-45
Williams HC. Clinical practice. Atopic dermatitis. N Engl J Med 2005; 352: 2314-2324.
https://doi.org/10.1056/NEJMcp042803 DOI: https://doi.org/10.1056/NEJMcp042803
Huang YJ, Marsland BJ, Bunyavanich S, O'Mahony L, Leung DY, Muraro A, 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: 1099-1110.
https://doi.org/10.1016/j.jaci.2017.02.007 DOI: https://doi.org/10.1016/j.jaci.2017.02.007
Dong TS, Gupta A. Influence of early life, diet, and the environment on the microbiome. Clin Gastroenterol Hepatol 2019; 17: 231-242.
https://doi.org/10.1016/j.cgh.2018.08.067 DOI: https://doi.org/10.1016/j.cgh.2018.08.067
Palmer CN, Irvine AD, Terron-Kwiatkowski A, Zhao Y, Liao H, Lee SP, et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 2006; 38: 441-446.
https://doi.org/10.1038/ng1767 DOI: https://doi.org/10.1038/ng1767
Hoste E, Kemperman P, Devos M, Denecker G, Kezic S, Yau N, et al. Caspase-14 is required for filaggrin degradation to natural moisturizing factors in the skin. J Invest Dermatol 2011; 131: 2233-2241.
https://doi.org/10.1038/jid.2011.153 DOI: https://doi.org/10.1038/jid.2011.153
Cookson WO, Ubhi B, Lawrence R, Abecasis GR, Walley AJ, Cox HE, et al. Genetic linkage of childhood atopic dermatitis to psoriasis susceptibility loci. Nat Genet 2001; 27: 372-373.
https://doi.org/10.1038/86867 DOI: https://doi.org/10.1038/86867
Irvine AD, McLean WH, Leung DY. Filaggrin mutations associated with skin and allergic diseases. N Engl J Med 2011; 365: 1315-1327.
https://doi.org/10.1056/NEJMra1011040 DOI: https://doi.org/10.1056/NEJMra1011040
Gupta J, Margolis DJ. Filaggrin gene mutations with special reference to atopic dermatitis. Curr Treat Options Allergy 2020; 7: 403-413.
https://doi.org/10.1007/s40521-020-00271-x DOI: https://doi.org/10.1007/s40521-020-00271-x
Sandilands A, Terron-Kwiatkowski A, Hull PR, O'Regan GM, Clayton TH, Watson RM, et al. Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema. Nat Genet 2007; 39: 650-654.
https://doi.org/10.1038/ng2020 DOI: https://doi.org/10.1038/ng2020
Brown SJ, Elias MS, Bradley M. Genetics in atopic dermatitis: historical perspective and future prospects. Acta Derm Venereol 2020; 100: adv00163.
https://doi.org/10.2340/00015555-3513 DOI: https://doi.org/10.2340/00015555-3513
Smith FJ, Irvine AD, Terron-Kwiatkowski A, Sandilands A, Campbell LE, Zhao Y, et al. Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris. Nat Genet 2006; 38: 337-342.
https://doi.org/10.1038/ng1743 DOI: https://doi.org/10.1038/ng1743
Fang Z, Li L, Zhang H, Zhao J, Lu W, Chen W. Gut microbiota, probiotics, and their interactions in prevention and treatment of atopic dermatitis: a review. Front Immunol 2021; 12: 720393.
https://doi.org/10.3389/fimmu.2021.720393 DOI: https://doi.org/10.3389/fimmu.2021.720393
Rigoni R, Fontana E, Dobbs K, Marrella V, Taverniti V, Maina V, et al. Cutaneous barrier leakage and gut inflammation drive skin disease in Omenn syndrome. J Allergy Clin Immunol 2020; 146: 1165-1179 e11.
https://doi.org/10.1016/j.jaci.2020.04.005 DOI: https://doi.org/10.1016/j.jaci.2020.04.005
Parodi A, Paolino S, Greco A, Drago F, Mansi C, Rebora A, et al. Small intestinal bacterial overgrowth in rosacea: clinical effectiveness of its eradication. Clin Gastroenterol Hepatol 2008; 6: 759-764.
https://doi.org/10.1016/j.cgh.2008.02.054 DOI: https://doi.org/10.1016/j.cgh.2008.02.054
FAO/WHO. Evaluation of health and nutritional properties of powder milk and live lactic acid bacteria. Joint FAO/WHO Expert Consultation Cordoba, Argentina, 2001: p. 2.
Fiocchi A, Pawankar R, Cuello-Garcia C, Ahn K, Al-Hammadi S, Agarwal A, et al. World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Probiotics. World Allergy Organ J 2015; 8: 4.
https://doi.org/10.1186/s40413-015-0055-2 DOI: https://doi.org/10.1186/s40413-015-0055-2
Cao L, Wang L, Yang L, Tao S, Xia R, Fan W. Long-term effect of early-life supplementation with probiotics on preventing atopic dermatitis: a meta-analysis. J Dermatolog Treat 2015; 26: 537-540.
https://doi.org/10.3109/09546634.2015.1027168 DOI: https://doi.org/10.3109/09546634.2015.1027168
Dotterud CK, Storro O, Johnsen R, Oien T. Probiotics in pregnant women to prevent allergic disease: a randomized, double-blind trial. Br J Dermatol 2010; 163: 616-623.
https://doi.org/10.1111/j.1365-2133.2010.09889.x DOI: https://doi.org/10.1111/j.1365-2133.2010.09889.x
Kim IS, Lee SH, Kwon YM, Adhikari B, Kim JA, Yu DY, et al. Oral administration of beta-glucan and lactobacillus plantarum alleviates atopic dermatitis-like symptoms. J Microbiol Biotechnol 2019; 29: 1693-1706.
https://doi.org/10.4014/jmb.1907.07011 DOI: https://doi.org/10.4014/jmb.1907.07011
D'Elios S, Trambusti I, Verduci E, Ferrante G, Rosati S, Marseglia GL, et al. Probiotics in the prevention and treatment of atopic dermatitis. Pediatr Allergy Immunol 2020; 31: 43-45.
https://doi.org/10.1111/pai.13364 DOI: https://doi.org/10.1111/pai.13364
Marsella R, Santoro D, Ahrens K, Thomas AL. Investigation of the effect of probiotic exposure on filaggrin expression in an experimental model of canine atopic dermatitis. Vet Dermatol 2013; 24: 260-e57.
https://doi.org/10.1111/vde.12006 DOI: https://doi.org/10.1111/vde.12006
Simpson MR, Dotterud CK, Storrø O, Johnsen R, Øien T. Perinatal probiotic supplementation in the prevention of allergy related disease: 6 year follow up of a randomised controlled trial. BMC Dermatol 2015; 15: 1-8.
https://doi.org/10.1186/s12895-015-0030-1 DOI: https://doi.org/10.1186/s12895-015-0030-1
Williams HC, Burney PG, Hay RJ, Archer CB, Shipley MJ, Hunter JJ, et al. The U.K. Working Party's Diagnostic Criteria for Atopic Dermatitis. I. Derivation of a minimum set of discriminators for atopic dermatitis. Br J Dermatol 1994; 131: 383-396.
https://doi.org/10.1111/j.1365-2133.1994.tb08530.x DOI: https://doi.org/10.1111/j.1365-2133.1994.tb08530.x
Emerson RM, Charman CR, Williams HC. The Nottingham Eczema Severity Score: preliminary refinement of the Rajka and Langeland grading. Br J Dermatol 2000; 142: 288-297.
https://doi.org/10.1046/j.1365-2133.2000.03300.x DOI: https://doi.org/10.1046/j.1365-2133.2000.03300.x
Meldgaard M, Szecsi PB, Carlsen BC, Thyssen JP, Johansen JD, Menne T, et al. A novel multiplex analysis of filaggrin polymorphisms: a universally applicable method for genotyping. Clin Chim Acta 2012; 413: 1488-1492.
https://doi.org/10.1016/j.cca.2012.06.014 DOI: https://doi.org/10.1016/j.cca.2012.06.014
Hoyer A, Rehbinder EM, Fardig M, Asad S, Lodrup Carlsen KC, Endre KMA, et al. Filaggrin mutations in relation to skin barrier and atopic dermatitis in early infancy. Br J Dermatol 2022; 186: 544-552.
https://doi.org/10.1111/bjd.20831 DOI: https://doi.org/10.1111/bjd.20831
Sun S, Chang G, Zhang L. The prevention effect of probiotics against eczema in children: an update systematic review and meta-analysis. J Dermatolog Treat 2021; 33: 1844-1854.
https://doi.org/10.1080/09546634.2021.1925077 DOI: https://doi.org/10.1080/09546634.2021.1925077
Nedoszytko B, Reszka E, Gutowska-Owsiak D, Trzeciak M, Lange M, Jarczak J, et al. Genetic and epigenetic aspects of atopic dermatitis. Int J Mol Sci 2020; 21: 1-18.
https://doi.org/10.3390/ijms21186484 DOI: https://doi.org/10.3390/ijms21186484
Forsberg A, Huoman J, Soderholm S, Bhai Mehta R, Nilsson L, Abrahamsson TR, et al. Pre- and postnatal lactobacillus reuteri treatment alters DNA methylation of infant T helper cells. Pediatr Allergy Immunol 2020; 31: 544-553.
https://doi.org/10.1111/pai.13240 DOI: https://doi.org/10.1111/pai.13240
Brown SJ, Relton CL, Liao H, Zhao Y, Sandilands A, Wilson IJ, et al. Filaggrin null mutations and childhood atopic eczema: a population-based case-control study. J Allergy Clin Immunol 2008; 121: 940-946.e3.
https://doi.org/10.1016/j.jaci.2008.01.013 DOI: https://doi.org/10.1016/j.jaci.2008.01.013
Brown SJ, Relton CL, Liao H, Zhao Y, Sandilands A, McLean WH, et al. Filaggrin haploinsufficiency is highly penetrant and is associated with increased severity of eczema: further delineation of the skin phenotype in a prospective epidemiological study of 792 school children. Br J Dermatol 2009; 161: 884-889.
https://doi.org/10.1111/j.1365-2133.2009.09339.x DOI: https://doi.org/10.1111/j.1365-2133.2009.09339.x
Loo EX, Shek LP, Goh A, Teoh OH, Chan YH, Soh SE, et al. Atopic dermatitis in early life: evidence for at least three phenotypes? Results from the GUSTO Study. Int Arch Allergy Immunol 2015; 166: 273-279.
https://doi.org/10.1159/000381342 DOI: https://doi.org/10.1159/000381342
Smieszek SP, Welsh S, Xiao C, Wang J, Polymeropoulos C, Birznieks G, et al. Correlation of age-of-onset of atopic dermatitis with filaggrin loss-of-function variant status. Sci Rep 2020; 10: 2721.
https://doi.org/10.1038/s41598-020-59627-7 DOI: https://doi.org/10.1038/s41598-020-59627-7
Kezic S, O'Regan GM, Yau N, Sandilands A, Chen H, Campbell LE, et al. Levels of filaggrin degradation products are influenced by both filaggrin genotype and atopic dermatitis severity. Allergy 2011; 66: 934-940.
https://doi.org/10.1111/j.1398-9995.2010.02540.x DOI: https://doi.org/10.1111/j.1398-9995.2010.02540.x
O'Regan GM, Kemperman PM, Sandilands A, Chen H, Campbell LE, Kroboth K, et al. Raman profiles of the stratum corneum define 3 filaggrin genotype-determined atopic dermatitis endophenotypes. J Allergy Clin Immunol 2010; 126: 574-580 e571.
https://doi.org/10.1016/j.jaci.2010.04.038 DOI: https://doi.org/10.1016/j.jaci.2010.04.038
Published
How to Cite
License
Copyright (c) 2024 Dinastry Pramadita Zakiudin, Jacob P. Thyssen, Claus Zachariae, Vibeke Videm, Torbjørn Øien, Melanie Rae Simpson
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All digitalized ActaDV contents is available freely online. The Society for Publication of Acta Dermato-Venereologica owns the copyright for all material published until volume 88 (2008) and as from volume 89 (2009) the journal has been published fully Open Access, meaning the authors retain copyright to their work.
Unless otherwise specified, all Open Access articles are published under CC-BY-NC licences, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material for non-commercial purposes, provided proper attribution to the original work.
