Oral tolerance induction and food allergy prevention
Oral tolerance induction and food allergy prevention
Keywords:immune factors, cord blood, breast milk, microbiota, elimination diet
This review aims to provide an overview of the issue of oral tolerance induction in early childhood and allergy manifestation. We discuss changes in epidemiology of allergic diseases that have occurred over the last decades in the context of current knowledge about environmental factors affecting prevalence of these diseases. Also this article presents current data about causes of "hygiene hypothesis" expansion to "microflora hypothesis" as well as an immunological background of this process; describes how immune factors of cord blood and breast milk, maternal and infant’s elimination diet, timing a solid food intake impact on immune system development and tolerance induction in early childhood. Current knowledge on issues of tolerance induction and allergy should induce update of allergy prevention recommendations in the nearest future.
Commins SP. Мechanisms of oral tolerance. Pediatr Clin North Am. 2015 Dec;62(6):1523–1529.
Aitoro R, Paparo L, Amoroso A, Di Costanzo M, Cosenza L, Granata V, et al. Gut microbiota as a target for preventive and therapeutic intervention against food allergy. Nutrients. 2017 Jun;9(7):672–684.
Stiemsma LT, Reynolds LA, Turvey SE, Finlay BB. The hygiene hypothesis: current perspectives and future therapies. Immunotargets and Ther. 2015 Jul;4:143–157.
Anandan C, Nurmatov U, van Schayck OC, Sheikh A. Is the prevalence of asthma declining? Systematic review of epidemiological studies. Allergy. 2010 Feb;65(2):152–167.
WHO. Noncommunicable diseases country profiles 2018. Geneva: World Health Organization; 2018.
Prüss‑Ustün A, van Deventer E, Mudu P, Campbell‑Lendrum D, Vickers C, Ivanov I, et al. Environmental risks and non‑communicable diseases. BMJ. 2019 Jan;364:I265.
Neerven RJJV, Savelkoul H. Nutrition and allergic diseases. Nutrients. 2017 Jul;9(7):762–770
Strachan DP. Hay fever, hygiene, and household size. BMJ. 1989 Nov; 299 (6710):1259–1260.
Ege MJ, Mayer M, Normand AC, Genuneit J, Cookson WO, Braun‑Fahrländer C, et al. Exposure to environmental microorganisms and childhood asthma. N Engl J Med. 2011 Feb; 364(8):701–709.
Ownby DR, Johnson CC, Peterson EL. Exposure to dogs and cats in the first year of life and risk of allergic sensitization at 6 to 7 years of age. JAMA. 2002 Aug;288(8):963–972.
Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986 Apr;136(7):2348–2357.
Holgate ST. Innate and adaptive immune responses in asthma. Nat Med. 2012 May;18(5):673–683.
Cording S, Fleissner D, Heimesaat MM, Bereswill S, Loddenkemper C, Uematsu S, et al. Commensal microbiota drive proliferation of conventional and Foxp3(+) regulatory CD4(+) T cells in mesenteric lymph nodes and Peyer’s patches. Eur J Microbiol Immunol (Bp). 2013 Mar;3(1):1–10.
Smith PM, Howitt MR, Panikov N., Michaud M, Gallini CA, Bohlooly‑Y M, et al. The microbial metabolites, short‑chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013 Aug;341(6145):569–573.
Sekirov I, Russell SL, Antunes LC, Finlay BB. Gut microbiota in health and disease. Physiol Rev. 2010 Jul;90(3):859–904.
Tamburini S, Shen N, Wu HC, Clemente JC. The microbiome in early life: Implications for health outcomes. Nat Med. 2016 Jul;22(7):713–722.
Eberl G. Immunity by equilibrium. Nat Rev Immunol. 2016 Jul;16(8):524–532.
Stefka AT, Feehley T, Tripathi P, Qiu J, McCoy K, Mazmanian SK, et al. Commensal bacteria protect against food allergen sensitization. Proc Natl Acad Sci USA. 2014 Sep;11(36):13145–13150.
Abrahamsson TR, Jakobsson HE, Andersson AF, Björkstén B, Engstrand L, Jenmalm MC. Low gut microbiota diversity in early infancy precedes asthma at school age. Clin Exp Allergy. 2014 Jun;44(6):842–850.
Hoskin‑Parr L, Teyhan A, Blocker A, Henderson AJW. Antibiotic exposure in the first two years of life and development of asthma and other allergic diseases by 7.5 yr: a dose‑dependent relationship. Pediatr Allergy Immunol. 2013 Dec;24(8):762–771.
Shaw SY, Blanchard JF, Bernstein CN. Association between the use of antibiotics and new diagnoses of Crohn’s disease and ulcerative colitis. Am J Gastroenterol. 2011 Dec;106(12):2133–2142.
Arrieta MC, Stiemsma LT, Amenyogbe N, Brown EM, Finlay B. The intestinal microbiome in early life: health and disease. Front Immunol. 2014 Sept;5:427.
Wopereis H, Oozeer R, Knipping K, Belzer C, Knol J. The ﬁrst thousand days — intestinal microbiology of early life: establishing a symbiosis. Pediatr Allergy Immunol. 2014 Aug;25(5):428–438.
Martin R, Makino H, Cetinyurek YA, Ben‑Amor K, Roelofs M, Ishikawa E, et al. Early‑life events, including mode of delivery and type of feeding, siblings and gender, shape the developing gut microbiota. PLoS One. 2016 Jun;11(6):e0158498.
Shulman ST, Friedmann HC, Sims RH. Theodor Escherich: the ﬁrst pediatric infectious diseases physician? Clin Infect Dis. 2007 Oct;45(8):1025–1029.
Koleva PT, Kim JS, Scott JA, Kozyrskyj AL. Microbial programming of health and disease starts during fetal life. Birth Defects Res C Embryo Today. 2015 Dec;105(4):265–277.
Collado MC, Rautava S, Aakko J, Isolauri E., Salminen S. Human gut colonization may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid. Sci Rep. 2016 Mar;6:23129.
Perez‑Muñoz МE, Arrieta M‑C, Ramer‑Tait AE, Walter J. A critical assessment of the “sterile womb” and “in utero colonization” hypotheses: implications for research on the pioneer infant microbiome. Microbiome. 2017 Apr;5:48.
Barker DJ, Osmond C, Golding J, Kuh D, Wadsworth ME. Growth in utero, blood pressure in childhood and adult life and mortality from cardiovascular disease. Br Med J. 1989 Mar;298(6673):564–567.
Urwin HJ, Miles EA, Noakes PS, Kremmyda LS, Vlachava M, Diaper N, et al. Effect of salmon consumption during pregnancy on maternal and infant faecal microbiota, secretory IgA and calprotectin. Br J Nutr. 2014 Mar;111(5):773–784.
Russell SL, Gold MJ, Willing BP, Thorson L, McNagny KM, Finlay BB. Perinatal antibiotic treatment affects murine microbiota, immune responses and allergic asthma. Gut Microbes. 2013 Mar;4(2):158–164.
Rajani PS, Seppo AE, Järvinen KM. Immunologically active components in human milk and development of atopic disease, with emphasis on food allergy, in the pediatric population. Front Pediatr. 2018 Aug;7(6):218.
Fernández L, Langaa S, Martína V, Maldonadoa A, Jiménez E, Martínd R, Rodríguez JM. The human milk microbiota: Origin and potential roles in health and disease. Pharm Research. 2013 Sept;69:1–10.
Pannaraj PS, Li Fan, Cerini C, Bender JM, Yang S, Rollie A, et al. Association between breast milk bacterial communities and establishment and development of the infant gut microbiome. JAMA Pediatr. 2017 May;171(7):647–654.
Medawar PB. Some immunological and endocrinological problems raised by the evolution of viviparity in vertebrates. Symposia of the Society for Experimental Biology. 1954 Sept;7:320–338
Morelli S, Mandal M, Goldsmith LT, Kashani BN, Ponzio N. The maternal immune system during pregnancy and its influence on fetal development. Research and Reports in Biology. 2015 Oct;6:171–189
Feliu J, Clay J, Raj K, Barber L, Devlia V, Shaw B, et al. Transplant‑acquired food allergy (TAFA) following cord blood stem cell transplantation in two adult patients with haematological malignancies. Br J Haematol. 2014 Nov;167(3):426–428.
Mori T, Kato J, Sakurai M, Kohashi S, Hashida R, Saburi M, et al. New‑onset food allergy following cord blood transplantation in adult patients. Bone Marrow Transplant. 2016 Feb;51(2):295–296.
Herberth G, Heinrich J, Röder S, Figl A, Weiss M, Diez U, et al. Reduced IFN‑γ and enhanced IL-4 producing CD4+ cord blood T cells are associated with a higher risk for atopic dermatitis during the ﬁrst 2 yr of life. Pediatr. Allergy Immunol. 2010 Feb;21:5–13
Meng Sh, Gao R, Yan B, Ren J, Wu F, Chen P, et al. Maternal allergic disease history affects childhood allergy development through impairment of neonatal regulatory T‑cells. Respiratory Research. 2016 Sept;17:114.
Fu Y, Lou H, Wang C, Lou W, Wang Y, Zheng T, et al. T cell subsets in cord blood are influenced by maternal allergy and associated with atopic dermatitis. Pediatr. Allergy Immunol. 2013 Mar;24(2):178–186.
Gallant MJ, Ellis AK. What can we learn about predictors of atopy from birth cohorts and cord blood biomarkers? Ann Allergy Asthma Immunol. 2018 Feb;120(2):138–144.
Chawes BL. Low‑grade disease activity in early life precedes childhood asthma and allergy. Dan Med J. 2016 Aug;63(8):B5272.
Chiu CY, Su KW, Tsai MH, Hua MC, Liao SL, Lai SH, et al. Low Mother‑to‑Child CCL22 chemokine levels are inversely related to mite sensitization and asthma in early childhood. Sci. Rep. 2018 Apr;8:6043.
Kuo‑Wei Y, Chiu CY, Kuan‑Wen S, Ming‑Han T, Man‑Chin H, Sui‑Ling L et al. High cord blood CCL22/CXCL10 chemokine ratios precede allergic sensitization in early childhood. Oncotarget. 2017 Jan;8(5):7384–7390.
Rochman Y, Dienger‑Stambaugh K, Richgels PK, Lewkowich IP, Kartashov AV, Barski A.,TSLP signaling in CD4+T cells programs a pathogenic T helper 2 cell state. Sci Signal. 2018 Mar;11(521):eaam8858.
Lupinek C, Hochwallner H, Johansson C, Mie A, Rigler E, Scheynius A, et al. Maternal allergen‑specific IgG might protect the child against allergic sensitization. J Allergy Clin Immunol. 2019 Jan;1:1–13.
Victor JR. Allergen‑specific IgG as a mediator of allergy inhibition: Lessons from mother to child. Hum Vaccin Immunother. 2017 Mar;13(3):507–513.
Valenta R, Hochwallner H, Linhart B, Pahr S. Food allergies: the basics. Gastroenterology. 2015 May;148(6):1120–1131.e4.
Gregory KE, Walker WA. Immunologic Factors in Human Milk and Disease Prevention in the Preterm Infant. Curr Pediatr Rep. 2013 Dec;1(4):222–228
Molès JP, Tuaillon E, Kankasa C, Bedin AS, Nagot N, Marchant A, et al. Breastmilk cell trafficking induces microchimerism‑mediated immune system maturation in the infant. Pediatr Allergy Immunol. 2018 Dec;29:133–143.
Murphy K. The mucosal immune system. In: Murphy K, Weaver C, editors. Janeway's immunobiology. 9th ed. New York: Garland Science/Taylor&Francis; 2017. p. 519–522.
Joseph CL, Havstad S, Bobbitt K, Woodcroft K, Zoratti EM, Nageotte C, et al. Transforming growth factor beta (TGFβ1) in breast milk and indicators of infant atopy in a birth cohort. Pediatr Allergy Immunol. 2014 May;25(3):257–263.
Morita Y, Campos‑Alberto E, Yamaide F, Nakano T, Ohnisi H, Kawamoto M, et al. TGF‑β сconcentration in breast milk is associated with the development of eczema in infants. Front Pediatr. 2018 Jun;6:162.
Munblit D, Treneva M, Peroni DG, Colicino S, Chow LY, Dissanayeke S, et al. Immune components in human milk are associated with early infant immunological health outcomes: A prospective three‑country analysis. Nutrients. 2017 Jun;9(6):532.
Snijders BE, Damoiseaux JG, Penders J, Kummeling I, Stelma FF, van Ree R, et al. Cytokines and soluble cd14 in breast milk in relation with atopic manifestations in mother and infant (KOALA study). Clin Exp Allergy. 2006 Dec;36(12):1609–1615.
Lodge CJ, Tan DJ, Lau MX, Dai X, Tham R, Lowe AJ, et al. Breastfeeding and asthma and allergies: A systematic review and meta‑analysis. Acta Paediatr. 2015 Dec;104(467):38–53.
Björkstén B, Aït‑Khaled N, Innes Asher M, Clayton TO, Robertson C. Global analysis of breast feeding and risk of symptoms of asthma, rhinoconjunctivitis and eczema in 6–7 year old children: ISAAC Phase Three Study Group. Allergol Immunopathol (Madr.). 2011 Nov‑Dec;39(6):318–325.
Saarinen UM, Kajosaari M. Breastfeeding as prophylaxis against atopic disease: Prospective follow‑up study until 17 years old. Lancet. 1995 Oct;346 (8982):1065–1069.
Järvinen KM, Bergmann KE, Bergmann R. Breast‑Always Best? In: Wahn U, Sampson HA, editors. Allergy, Immunity and Tolerance in Early Childhood: The First Steps of the Atopic March. New York: Elsevier; 2016. p. 235–260.
Kramer MS. Does breast feeding help protect against atopic disease? Biology, methodology, and a golden jubilee of controversy. J Pediatr. 1988 Feb;112(2):181–190.
Peroni DG, Pescollderungg L, Piacentini GL, Rigotti E, Maselli M, Watschinger K, et al. Immune regulatory cytokines in the milk of lactating women from farming and urban environments. Pediatr Allergy Immunol. 2010 Sep;21(6):977–982.
Holmlund U, Amoudruz P, Johansson MA, Haileselassie Y, Ongoiba A, Kayentao K, et al. Maternal country of origin, breast milk characteristics and potential inﬂuences on immunity in offspring. Clin Exp Immunol. 2010 Dec;162(3):500–509.
Järvinen KM. Variations in Human Milk Composition: Impact on Immune Development and Allergic Disease Susceptibility. Breastfeed Med. 2018 Apr;13(S1):S11–S13.
Munblit D, Boyle RJ, Warner JO. Factors affecting breast milk composition and potential consequences for development of the allergic phenotype. Clin Exp Allergy. 2015 Mar;45(3):583–601.
Gay MCL, Koleva PT, Slupsky CM, Toit ED, Eggesbo M, Johnson CC, et al. Worldwide variation in human milk metabolome: indicators of breast physiology and maternal lifestyle? Nutrients. 2018 Aug;10(9):pii:E1151.
Hurley WL, Theil PK. Perspectives on immunoglobulins in colostrum and milk. Nutrients. 2011 Apr;3(4):442–474.
Järvinen KM, Westfall JE, Seppo MS, James AK, Tsuang AJ, Feustel PJ, et al. Role of maternal elimination diets and human milk IgA in development of cow’s milk allergy in the infants. Clin Exp Allergy. 2014 Jan;44(1):69–78.
Natsume O, Ohya Y. Recent advancement to prevent the development of allergy and allergic diseases and therapeutic strategy in the perspective of barrier dysfunction. Allergology International. 2018 Jan;67(1):24–31
Tran MM, Lefebvre DL, Dai D, Dharma C, Subbarao P, Lou W, et al. Timing of food introduction and development of food sensitization in a prospective birth cohort. Pediatr Allergy Immunol. 2017 Aug;28(5):471–477.
Prescott SL, Smith P, Tang M, Palmer DJ, Sinn J, Huntley SJ, et al. The importance of early complementary feeding in the development of oral tolerance: concerns and controversies. Pediatr Allergy Immunol. 2008 Aug;19(5):375–380.
How to Cite
Copyright (c) 2019 Natallia Tsikhan, Mikhail Belevtsev
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.