Microbiota and Food Allergy

  • Shang-An Shu
  • Agatha W. T. Yuen
  • Elena Woo
  • Ka-Hou Chu
  • Hoi-Shan Kwan
  • Guo-Xiang Yang
  • Yao Yang
  • Patrick S. C. LeungEmail author


Emerging evidence suggests that the increasing prevalence of food allergies is associated with compositional and functional changes in our gut microbiota. Microbiota-host interactions play a key role in regulating the immune system. Development of a healthy gut microbiota and immune system occurs early in life and is largely shaped by exposure to maternal microbes through vaginal/natural delivery and breast milk, whereas use of antibiotics can disrupt gut homeostasis and significantly raise the risk of allergic diseases. Thus, changes in the quantity or diversity of gut microbes affect oral toleranace through interations of microbial molecules with pattern recognition receptors on immune cells and confer susceptibility to food allergies. On the other hand, short chain fatty acids which are fermentation end products of insoluble fibers by intestinal micoorganisms have been shown to confer protective effects on food allergy. As a preventive and therapeutic treatment for food allergies, probiotics have gained widespread attention in recent years. Reintroducing certain commensal microbes, such as Clostridia, both in animal models and clinical trials led to the prevention or resolution of allergic symptoms. This review highlights recent progress in our understanding of the gut microbiota’s role in food allergy. However, mechanistic details underlying the anti-allergic effects of probiotics and the interaction between the gut microbiota and the immune system remain circumstantial and are not fully understood. Future studies should address possible factors and underlying mechanisms for microbiota-host interactions and gut immunity, as well as the efficacy, safety, and appropriate use of probiotics in establishing a standard treatment regimen for food allergies.


Hygiene hypothesis Microbe-host interactions Intestinal microbiota Food antigens Tolerance Probiotics Short-chain fatty acids 





Bifidobacterium infantis




cow’s milk allergy


cow milk protein


dendritic cells


enterobacteriaceae and bacterioidaceae ratio


extensively hydrolyzed casein formula


Food and Agriculture Organization


gut-associated lymphoid tissues


G protein-couple receptors


immunoglobulin-like transcript




Lactobacillus casei strain shirota (LcS)


ovalbumin-specific t cell receptor transgenic mice


lactic acid bacteria


Lactobacillus GG




mesenteric lymph nodes


outer membrane


pattern-recognition receptors


polyunsaturated fatty acids


retinoic acid


short-chain fatty acids


secretory IgA


toll-like receptors


regulatory T cells


World Health Organization


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. 1.
    Ortqvist A et al (2018) Impact of repeated influenza vaccinations in persons over 65 years of age: a large population-based cohort study of severe influenza over six consecutive seasons, 2011/12-2016/17. Vaccine 36(37):5556-5564.Google Scholar
  2. 2.
    Lopez A, Mariette X, Bachelez H, Belot A, Bonnotte B, Hachulla E, Lahfa M, Lortholary O, Loulergue P, Paul S, Roblin X, Sibilia J, Blum M, Danese S, Bonovas S, Peyrin-Biroulet L (2017) Vaccination recommendations for the adult immunosuppressed patient: a systematic review and comprehensive field synopsis. J Autoimmun 80:10–27PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Chinthrajah RS, Hernandez JD, Boyd SD, Galli SJ, Nadeau KC (2016) Molecular and cellular mechanisms of food allergy and food tolerance. J Allergy Clin Immunol 137(4):984–997PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Azad MB, Konya T, Guttman DS, Field CJ, Sears MR, HayGlass KT, Mandhane PJ, Turvey SE, Subbarao P, Becker AB, Scott JA, Kozyrskyj AL, the CHILD Study Investigators (2015) Infant gut microbiota and food sensitization: associations in the first year of life. Clin Exp Allergy 45(3):632–643PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Geuking MB, Cahenzli J, Lawson MAE, Ng DCK, Slack E, Hapfelmeier S, McCoy KD, Macpherson AJ (2011) Intestinal bacterial colonization induces mutualistic regulatory T cell responses. Immunity 34(5):794–806CrossRefGoogle Scholar
  6. 6.
    Plunkett CH, Nagler CR (2017) The influence of the microbiome on allergic sensitization to food. J Immunol 198(2):581–589PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Cossu M et al (2018) Unmet needs in systemic sclerosis understanding and treatment: the knowledge gaps from a scientist’s, clinician’s, and patient’s perspective. Clin Rev Allergy Immunol 55(3):312–331.Google Scholar
  8. 8.
    Dowling PJ, Neuhaus H, Polk BI (2018) The role of the environment in eosinophilic esophagitis. Clin Rev Allergy Immunol
  9. 9.
    Rook GA (2012) Hygiene hypothesis and autoimmune diseases. Clin Rev Allergy Immunol 42(1):5–15PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Zaheer M, Wang C, Bian F, Yu Z, Hernandez H, de Souza RG, Simmons KT, Schady D, Swennes AG, Pflugfelder SC, Britton RA, de Paiva CS (2018) Protective role of commensal bacteria in Sjogren syndrome. J Autoimmun 93:45–56PubMedCrossRefGoogle Scholar
  11. 11.
    Bunyavanich S, Shen N, Grishin A, Wood R, Burks W, Dawson P, Jones SM, Leung DYM, Sampson H, Sicherer S, Clemente JC (2016) Early-life gut microbiome composition and milk allergy resolution. J Allergy Clin Immunol 138(4):1122–1130PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Igetei JE, el-Faham M, Liddell S, Doenhoff MJ (2017) Antigenic cross-reactivity between Schistosoma mansoni and peanut: a role for cross-reactive carbohydrate determinants (CCDs) and implications for the hygiene hypothesis. Immunology 150(4):506–517PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Johnston CJC, Smyth DJ, Kodali RB, White MPJ, Harcus Y, Filbey KJ, Hewitson JP, Hinck CS, Ivens A, Kemter AM, Kildemoes AO, le Bihan T, Soares DC, Anderton SM, Brenn T, Wigmore SJ, Woodcock HV, Chambers RC, Hinck AP, McSorley HJ, Maizels RM (2017) A structurally distinct TGF-beta mimic from an intestinal helminth parasite potently induces regulatory T cells. Nat Commun 8(1):1741PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Stefka AT, Feehley T, Tripathi P, Qiu J, McCoy K, Mazmanian SK, Tjota MY, Seo GY, Cao S, Theriault BR, Antonopoulos DA, Zhou L, Chang EB, Fu YX, Nagler CR (2014) Commensal bacteria protect against food allergen sensitization. Proc Natl Acad Sci 111(36):13145–13150PubMedCrossRefGoogle Scholar
  15. 15.
    Turcanu V, Brough HA, du Toit G, Foong RX, Marrs T, Santos AF, Lack G (2017) Immune mechanisms of food allergy and its prevention by early intervention. Curr Opin Immunol 48:92–98PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Round JL, Mazmanian SK (2009) The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 9(5):313–323PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Backhed F et al (2005) Host-bacterial mutualism in the human intestine. Science 307(5717):1915–1920PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Gill SR, Pop M, DeBoy RT, Eckburg PB, Turnbaugh PJ, Samuel BS, Gordon JI, Relman DA, Fraser-Liggett CM, Nelson KE (2006) Metagenomic analysis of the human distal gut microbiome. Science 312(5778):1355–1359PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Blazquez AB, Berin MC (2017) Microbiome and food allergy. Transl Res 179:199–203PubMedCrossRefGoogle Scholar
  20. 20.
    Koenig JE et al (2011) Succession of microbial consortia in the developing infant gut microbiome. Proc Natl Acad Sci 108(Supplement 1):4578–4585PubMedCrossRefGoogle Scholar
  21. 21.
    Nuriel-Ohayon M, Neuman H, Koren O (2016) Microbial changes during pregnancy, birth, and infancy. Front Microbiol 7:1031PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Martin R, Nauta A, Ben Amor K, Knippels L, Knol J, Garssen J (2010) Early life: gut microbiota and immune development in infancy. Benefic Microbes 1(4):367–382CrossRefGoogle Scholar
  23. 23.
    Fazlollahi M, Chun Y, Grishin A, Wood RA, Burks AW, Dawson P, Jones SM, Leung DYM, Sampson HA, Sicherer SH, Bunyavanich S (2018) Early-life gut microbiome and egg allergy. Allergy 73(7):1515–1524PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Savage JH, Lee-Sarwar KA, Sordillo J, Bunyavanich S, Zhou Y, O'Connor G, Sandel M, Bacharier LB, Zeiger R, Sodergren E, Weinstock GM, Gold DR, Weiss ST, Litonjua AA (2018) A prospective microbiome-wide association study of food sensitization and food allergy in early childhood. Allergy 73(1):145–152PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Lee E, Kim BJ, Kang MJ, Choi KY, Cho HJ, Kim Y, Yang SI, Jung YH, Kim HY, Seo JH, Kwon JW, Kim HB, Lee SY, Hong SJ (2016) Dynamics of gut microbiota according to the delivery mode in healthy Korean infants. Allergy, Asthma Immunol Res 8(5):471–477CrossRefGoogle Scholar
  26. 26.
    Abrahamsson TR et al (2012) Low diversity of the gut microbiota in infants with atopic eczema. J Allergy Clin Immunol 129(2):434–440 440 e1–2PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Chen CC, Chen KJ, Kong MS, Chang HJ, Huang JL (2016) Alterations in the gut microbiotas of children with food sensitization in early life. Pediatr Allergy Immunol 27(3):254–262PubMedCrossRefGoogle Scholar
  28. 28.
    Song H, Yoo Y, Hwang J, Na YC, Kim HS (2016) Faecalibacterium prausnitzii subspecies–level dysbiosis in the human gut microbiome underlying atopic dermatitis. J Allergy Clin Immunol 137(3):852–860PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Berni Canani R, Gilbert JA, Nagler CR (2015) The role of the commensal microbiota in the regulation of tolerance to dietary allergens. Curr Opin Allergy Clin Immunol 15(3):243–249PubMedCrossRefGoogle Scholar
  30. 30.
    Jakobsson HE, Abrahamsson TR, Jenmalm MC, Harris K, Quince C, Jernberg C, Björkstén B, Engstrand L, Andersson AF (2014) Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by caesarean section. Gut 63(4):559–566PubMedCrossRefGoogle Scholar
  31. 31.
    Abelius MS, Lempinen E, Lindblad K, Ernerudh J, Berg G, Matthiesen L, Nilsson LJ, Jenmalm MC (2014) Th2-like chemokine levels are increased in allergic children and influenced by maternal immunity during pregnancy. Pediatr Allergy Immunol 25(4):387–393PubMedCrossRefGoogle Scholar
  32. 32.
    Jiménez E, Marín ML, Martín R, Odriozola JM, Olivares M, Xaus J, Fernández L, Rodríguez JM (2008) Is meconium from healthy newborns actually sterile? Res Microbiol 159(3):187–193PubMedCrossRefGoogle Scholar
  33. 33.
    Pannaraj PS, Li F, Cerini C, Bender JM, Yang S, Rollie A, Adisetiyo H, Zabih S, Lincez PJ, Bittinger K, Bailey A, Bushman FD, Sleasman JW, Aldrovandi GM (2017) Association between breast milk bacterial communities and establishment and development of the infant gut microbiome. JAMA Pediatr 171:647–654PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Rautava S, Luoto R, Salminen S, Isolauri E (2012) Microbial contact during pregnancy, intestinal colonization and human disease. Nat Rev Gastroenterol Hepatol 9(10):565–576PubMedCrossRefGoogle Scholar
  35. 35.
    Fernández L, Langa S, Martín V, Maldonado A, Jiménez E, Martín R, Rodríguez JM (2013) The human milk microbiota: origin and potential roles in health and disease. Pharmacol Res 69(1):1–10PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Ardeshir A et al (2014) Breast-fed and bottle-fed infant rhesus macaques develop distinct gut microbiotas and immune systems. Sci Transl Med 6(252):252ra120–252ra120PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Rogier EW, Frantz AL, Bruno MEC, Wedlund L, Cohen DA, Stromberg AJ, Kaetzel CS (2014) Secretory antibodies in breast milk promote long-term intestinal homeostasis by regulating the gut microbiota and host gene expression. Proc Natl Acad Sci 111(8):3074–3079PubMedCrossRefGoogle Scholar
  38. 38.
    Skypala IJ, McKenzie R (2018) Nutritional issues in food allergy. Clin Rev Allergy Immunol
  39. 39.
    Jernberg C, Lofmark S, Edlund C, Jansson JK (2010) Long-term impacts of antibiotic exposure on the human intestinal microbiota. Microbiology 156(11):3216–3223PubMedCrossRefGoogle Scholar
  40. 40.
    Modi SR, Collins JJ, Relman DA (2014) Antibiotics and the gut microbiota. J Clin Invest 124(10):4212–4218PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Metsälä J, Lundqvist A, Virta LJ, Kaila M, Gissler M, Virtanen SM (2015) Prenatal and post-natal exposure to antibiotics and risk of asthma in childhood. Clin Exp Allergy 45(1):137–145PubMedCrossRefGoogle Scholar
  42. 42.
    Korpela K, Salonen A, Virta LJ, Kekkonen RA, Forslund K, Bork P, de Vos WM (2016) Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children. Nat Commun 7:10410PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Lapin B, Piorkowski J, Ownby D, Freels S, Chavez N, Hernandez E, Wagner-Cassanova C, Pelzel D, Vergara C, Persky V (2015) Relationship between prenatal antibiotic use and asthma in at-risk children. Ann Allergy Asthma Immunol 114(3):203–207PubMedCrossRefGoogle Scholar
  44. 44.
    Persaud RR, Azad MB, Chari RS, Sears MR, Becker AB, Kozyrskyj AL, the CHILD Study Investigators (2015) Perinatal antibiotic exposure of neonates in Canada and associated risk factors: a population-based study. J Matern Fetal Neonatal Med 28(10):1190–1195PubMedCrossRefGoogle Scholar
  45. 45.
    Azad M, Konya T, Persaud RR, Guttman DS, Chari RS, Field CJ, Sears MR, Mandhane PJ, Turvey SE, Subbarao P, Becker AB, Scott JA, Kozyrskyj AL, the CHILD Study Investigators (2016) Impact of maternal intrapartum antibiotics, method of birth and breastfeeding on gut microbiota during the first year of life: a prospective cohort study. BJOG Int J Obstet Gynaecol 123(6):983–993CrossRefGoogle Scholar
  46. 46.
    Love BL et al (2016) Antibiotic prescription and food allergy in young children. Allergy Asthma Clin Immunol 12(1):41PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Hirsch AG, Pollak J, Glass TA, Poulsen MN, Bailey-Davis L, Mowery J, Schwartz BS (2017) Early-life antibiotic use and subsequent diagnosis of food allergy and allergic diseases. Clin Exp Allergy 47(2):236–244PubMedCrossRefGoogle Scholar
  48. 48.
    Han Y-Y, Forno E, Badellino HA, Celedón JC (2017) Antibiotic use in early life, rural residence, and allergic diseases in Argentinean children. J Allergy Clin Immunol Pract 5:1112–1118.e2PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Tordesillas L, Berin MC (2018) Mechanisms of oral tolerance. Clin Rev Allergy Immunol 55:107–117PubMedCrossRefGoogle Scholar
  50. 50.
    Nowak-Wegrzyn A, Szajewska H, Lack G (2017) Food allergy and the gut. Nat Rev Gastroenterol Hepatol 14(4):241–257PubMedCrossRefGoogle Scholar
  51. 51.
    Kim JS, Sampson HA (2012) Food allergy: a glimpse into the inner workings of gut immunology. Curr Opin Gastroenterol 28(2):99–103PubMedCrossRefGoogle Scholar
  52. 52.
    Clarke K, Chintanaboina J (2018) Allergic and immunologic perspectives of inflammatory bowel disease. Clin Rev Allergy Immuno.
  53. 53.
    Hartono S, Ippoliti MR, Mastroianni M, Torres R, Rider NL (2018) Gastrointestinal disorders associated with primary immunodeficiency diseases. Clin Rev Allergy Immunol
  54. 54.
    Chen B, Sun L, Zhang X (2017) Integration of microbiome and epigenome to decipher the pathogenesis of autoimmune diseases. J Autoimmun 83:31–42PubMedCrossRefGoogle Scholar
  55. 55.
    Ueno A, Jeffery L, Kobayashi T, Hibi T, Ghosh S, Jijon H (2018) Th17 plasticity and its relevance to inflammatory bowel disease. J Autoimmun 87:38–49PubMedCrossRefGoogle Scholar
  56. 56.
    Cahenzli J, Köller Y, Wyss M, Geuking MB, McCoy KD (2013) Intestinal microbial diversity during early-life colonization shapes long-term IgE levels. Cell Host Microbe 14(5):559–570PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    McCoy KD, Harris NL, Diener P, Hatak S, Odermatt B, Hangartner L, Senn BM, Marsland BJ, Geuking MB, Hengartner H, Macpherson AJS, Zinkernagel RM (2006) Natural IgE production in the absence of MHC class II cognate help. Immunity 24(3):329–339PubMedCrossRefGoogle Scholar
  58. 58.
    Tan J, McKenzie C, Vuillermin PJ, Goverse G, Vinuesa CG, Mebius RE, Macia L, Mackay CR (2016) Dietary fiber and bacterial SCFA enhance oral tolerance and protect against food allergy through diverse cellular pathways. Cell Rep 15(12):2809–2824PubMedCrossRefGoogle Scholar
  59. 59.
    Wannemuehler M et al (1982) Lipopolysaccharide (LPS) regulation of the immune response: LPS converts germfree mice to sensitivity to oral tolerance induction. J Immunol 129(3):959–965PubMedGoogle Scholar
  60. 60.
    Hacini-Rachinel F et al (2018) Intestinal dendritic cell licensing through Toll-like receptor 4 is required for oral tolerance in allergic contact dermatitis. J Allergy Clin Immunol 141(1):163–170.Google Scholar
  61. 61.
    Wang S, Charbonnier LM, Noval Rivas M, Georgiev P, Li N, Gerber G, Bry L, Chatila TA (2015) MyD88 adaptor-dependent microbial sensing by regulatory T cells promotes mucosal tolerance and enforces commensalism. Immunity 43(2):289–303PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, Edberg S, Medzhitov R (2004) Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 118(2):229–241PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Ye H, Arron JR, Lamothe B, Cirilli M, Kobayashi T, Shevde NK, Segal D, Dzivenu OK, Vologodskaia M, Yim M, du K, Singh S, Pike JW, Darnay BG, Choi Y, Wu H (2002) Distinct molecular mechanism for initiating TRAF6 signalling. Nature 418(6896):443–447PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Han D, Walsh MC, Cejas PJ, Dang NN, Kim YF, Kim J, Charrier-Hisamuddin L, Chau L, Zhang Q, Bittinger K, Bushman FD, Turka LA, Shen H, Reizis B, DeFranco AL, Wu GD, Choi Y (2013) Dendritic cell expression of the signaling molecule TRAF6 is critical for gut microbiota-dependent immune tolerance. Immunity 38(6):1211–1222PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Han D, Walsh MC, Kim KS, Hong SW, Lee J, Yi J, Rivas G, Surh CD, Choi Y (2015) Microbiota-independent ameliorative effects of antibiotics on spontaneous th2-associated pathology of the small intestine. PLoS One 10(2):e0118795PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G, Takahashi D, Nakanishi Y, Uetake C, Kato K, Kato T, Takahashi M, Fukuda NN, Murakami S, Miyauchi E, Hino S, Atarashi K, Onawa S, Fujimura Y, Lockett T, Clarke JM, Topping DL, Tomita M, Hori S, Ohara O, Morita T, Koseki H, Kikuchi J, Honda K, Hase K, Ohno H (2013) Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504(7480):446–450PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Rivas MN et al (2013) A microbiota signature associated with experimental food allergy promotes allergic sensitization and anaphylaxis. J Allergy Clin Immunol 131(1):201–212CrossRefGoogle Scholar
  68. 68.
    Lee J-B et al (2016) IL-25 and CD4+ T H 2 cells enhance type 2 innate lymphoid cell–derived IL-13 production, which promotes IgE-mediated experimental food allergy. J Allergy Clin Immunol 137(4):1216–1225 e5PubMedCrossRefGoogle Scholar
  69. 69.
    David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA, Biddinger SB, Dutton RJ, Turnbaugh PJ (2014) Diet rapidly and reproducibly alters the human gut microbiome. Nature 505(7484):559–563PubMedCrossRefGoogle Scholar
  70. 70.
    Louis P, Hold GL, Flint HJ (2014) The gut microbiota, bacterial metabolites and colorectal cancer. Nat Rev Microbiol 12(10):661–672PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Tan J et al (2014) The role of short-chain fatty acids in health and disease. Adv Immunol 121(91):e119Google Scholar
  72. 72.
    Trompette A, Gollwitzer ES, Yadava K, Sichelstiel AK, Sprenger N, Ngom-Bru C, Blanchard C, Junt T, Nicod LP, Harris NL, Marsland BJ (2014) Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat Med 20(2):159–166PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Goverse G, Molenaar R, Macia L, Tan J, Erkelens MN, Konijn T, Knippenberg M, Cook ECL, Hanekamp D, Veldhoen M, Hartog A, Roeselers G, Mackay CR, Mebius RE (2017) Diet-derived short chain fatty acids stimulate intestinal epithelial cells to induce mucosal tolerogenic dendritic cells. J Immunol 198(5):2172–2181PubMedCrossRefPubMedCentralGoogle Scholar
  74. 74.
    Koh A, de Vadder F, Kovatcheva-Datchary P, Bäckhed F (2016) From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell 165(6):1332–1345PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Park J, Kim M, Kang SG, Jannasch AH, Cooper B, Patterson J, Kim CH (2015) Short chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR-S6K pathway. Mucosal Immunol 8(1):80–93PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    Mortha A, Chudnovskiy A, Hashimoto D, Bogunovic M, Spencer SP, Belkaid Y, Merad M (2014) Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis. Science 343(6178):1249288PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Virkud YV, Wang J, Shreffler WG (2018) Enhancing the safety and efficacy of food allergy immunotherapy: a review of adjunctive therapies. Clin Rev Allergy Immunol 55:172–189PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Food and Agriculture Organization of the United Nations, W.H.O (2002) Guidelines for the evaluation of probiotics in food. World Health OrganisationGoogle Scholar
  79. 79.
    Hoarau C, Lagaraine C, Martin L, Velge-Roussel F, Lebranchu Y (2006) Supernatant of Bifidobacterium breve induces dendritic cell maturation, activation, and survival through a toll-like receptor 2 pathway. J Allergy Clin Immunol 117(3):696–702PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Song S, Lee SJ, Park DJ, Oh S, Lim KT (2016) The anti-allergic activity of lactobacillus plantarum L67 and its application to yogurt. J Dairy Sci 99(12):9372–9382PubMedCrossRefGoogle Scholar
  81. 81.
    Xiao JZ et al (2006) Effect of probiotic Bifidobacterium longum BB536 [corrected] in relieving clinical symptoms and modulating plasma cytokine levels of Japanese cedar pollinosis during the pollen season. A randomized double-blind, placebo-controlled trial. J Investig Allergol Clin Immunol 16(2):86–93PubMedPubMedCentralGoogle Scholar
  82. 82.
    Murosaki S, Yamamoto Y, Ito K, Inokuchi T, Kusaka H, Ikeda H, Yoshikai Y (1998) Heat-killed Lactobacillus plantarum L-137 suppresses naturally fed antigen–specific IgE production by stimulation of IL-12 production in mice. J Allergy Clin Immunol 102(1):57–64PubMedCrossRefGoogle Scholar
  83. 83.
    Shida K, Takahashi R, Iwadate E, Takamizawa K, Yasui H, Sato T, Habu S, Hachimura S, Kaminogawa S (2002) Lactobacillus casei strain Shirota suppresses serum immunoglobulin E and immunoglobulin G1 responses and systemic anaphylaxis in a food allergy model. Clin Exp Allergy 32(4):563–570PubMedCrossRefPubMedCentralGoogle Scholar
  84. 84.
    Nawaz M, Ma C, Basra MAR, Wang J, Xu J (2015) Amelioration of ovalbumin induced allergic symptoms in Balb/c mice by potentially probiotic strains of lactobacilli. Benefic Microbes 6(5):669–678CrossRefGoogle Scholar
  85. 85.
    Aitoro R, Simeoli R, Amoroso A, Paparo L, Nocerino R, Pirozzi C, di Costanzo M, Meli R, de Caro C, Picariello G, Mamone G, Calignano A, Nagler CR, Berni Canani R (2017) Extensively hydrolyzed casein formula alone or with L. rhamnosus GG reduces β-lactoglobulin sensitization in mice. Pediatr Allergy Immunol 28(3):230–237PubMedCrossRefPubMedCentralGoogle Scholar
  86. 86.
    Thang CL et al (2011) Effects of Lactobacillus rhamnosus GG supplementation on cow's milk allergy in a mouse model. Allergy, Asthma Clin Immunol 7(1):20CrossRefGoogle Scholar
  87. 87.
    Sarowska J, Choroszy-Król I, Regulska-Ilow B, Frej-Mądrzak M, Jama-Kmiecik A (2013) The therapeutic effect of probiotic bacteria on gastrointestinal diseases. Adv Clin Exp Med 22(5):759–766PubMedPubMedCentralGoogle Scholar
  88. 88.
    Castellazzi AM et al (2013) Probiotics and food allergy. Ital J Pediatr 39(1):47PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Servin AL (2004) Antagonistic activities of lactobacilli and bifidobacteria against microbial pathogens. FEMS Microbiol Rev 28(4):405–440PubMedCrossRefPubMedCentralGoogle Scholar
  90. 90.
    Chauviere G et al (1992) Competitive exclusion of diarrheagenic Escherichia coli (ETEC) from human enterocyte-like Caco-2 cells by heat-killed Lactobacillus. FEMS Microbiol Lett 70(3):213–217PubMedCrossRefGoogle Scholar
  91. 91.
    Blum S, Haller D, Pfeifer A, Schiffrin EJ (2002) Probiotics and immune response. Clin Rev Allergy Immunol 22(3):287–309PubMedCrossRefGoogle Scholar
  92. 92.
    Xu H, Jeong HS, Lee HY, Ahn J (2009) Assessment of cell surface properties and adhesion potential of selected probiotic strains. Lett Appl Microbiol 49(4):434–442PubMedCrossRefGoogle Scholar
  93. 93.
    O'Toole PW, Cooney JC (2008) Probiotic bacteria influence the composition and function of the intestinal microbiota. Interdiscip Perspect Infect Dis 2008:175285PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Bermudez-Brito M, Plaza-Díaz J, Muñoz-Quezada S, Gómez-Llorente C, Gil A (2012) Probiotic mechanisms of action. Ann Nutr Metab 61(2):160–174PubMedCrossRefGoogle Scholar
  95. 95.
    Musikasang H, Sohsomboon N, Tani A, Maneerat S (2012) Bacteriocin-producing lactic acid bacteria as a probiotic potential from Thai indigenous chickens. Czeh J Anim Sci 57:137–149CrossRefGoogle Scholar
  96. 96.
    Dobson A, Cotter PD, Ross RP, Hill C (2012) Bacteriocin production: a probiotic trait? Appl Environ Microbiol 78(1):1–6PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Vandenbergh PA (1993) Lactic acid bacteria, their metabolic products and interference with microbial growth. FEMS Microbiol Rev 12(1–3):221–237CrossRefGoogle Scholar
  98. 98.
    Alakomi H-L, Skytta E, Saarela M, Mattila-Sandholm T, Latva-Kala K, Helander IM (2000) Lactic acid permeabilizes gram-negative bacteria by disrupting the outer membrane. Appl Environ Microbiol 66(5):2001–2005PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Rizzetto L, Fava F, Tuohy KM, Selmi C (2018) Connecting the immune system, systemic chronic inflammation and the gut microbiome: the role of sex. J Autoimmun 92:12–34PubMedCrossRefGoogle Scholar
  100. 100.
    Özdemir Ö (2010) Various effects of different probiotic strains in allergic disorders: an update from laboratory and clinical data. Clin Exp Immunol 160(3):295–304PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Muraro A, Werfel T, Hoffmann-Sommergruber K, Roberts G, Beyer K, Bindslev-Jensen C, Cardona V, Dubois A, duToit G, Eigenmann P, Fernandez Rivas M, Halken S, Hickstein L, Høst A, Knol E, Lack G, Marchisotto MJ, Niggemann B, Nwaru BI, Papadopoulos NG, Poulsen LK, Santos AF, Skypala I, Schoepfer A, van Ree R, Venter C, Worm M, Vlieg-Boerstra B, Panesar S, de Silva D, Soares-Weiser K, Sheikh A, Ballmer-Weber BK, Nilsson C, de Jong NW, Akdis CA, the EAACI Food Allergy and Anaphylaxis Guidelines Group (2014) EAACI food allergy and anaphylaxis guidelines: diagnosis and management of food allergy. Allergy 69(8):1008–1025PubMedCrossRefPubMedCentralGoogle Scholar
  102. 102.
    Parekh H, Bahna SL (2016) Infant formulas for food allergy treatment and prevention. Pediatr Ann 45(4):e150–e156PubMedCrossRefGoogle Scholar
  103. 103.
    Silva D et al (2014) Primary prevention of food allergy in children and adults: systematic review. Allergy 69(5):581–589PubMedCrossRefPubMedCentralGoogle Scholar
  104. 104.
    Canani RB et al (2017) Extensively hydrolyzed casein formula containing Lactobacillus rhamnosus GG reduces the occurrence of other allergic manifestations in children with cow’s milk allergy: 3-year randomized controlled trial. J Allergy Clin Immunol 139(6):1906–1913 e4CrossRefGoogle Scholar
  105. 105.
    Yang B, Xiao L, Liu S, Liu X, Luo Y, Ji Q, Yang P, Liu Z (2017) Exploration of the effect of probiotics supplementation on intestinal microbiota of food allergic mice. Am J Transl Res 9(2):376–385PubMedPubMedCentralGoogle Scholar
  106. 106.
    Canani RB et al (2016) Lactobacillus rhamnosus GG-supplemented formula expands butyrate-producing bacterial strains in food allergic infants. ISME J 10(3):742–750CrossRefGoogle Scholar
  107. 107.
    Cox MJ, Huang YJ, Fujimura KE, Liu JT, McKean M, Boushey HA, Segal MR, Brodie EL, Cabana MD, Lynch SV (2010) Lactobacillus casei abundance is associated with profound shifts in the infant gut microbiome. PLoS One 5(1):e8745PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Cosenza L, Nocerino R, di Scala C, di Costanzo M, Amoroso A, Leone L, Paparo L, Pezzella C, Aitoro R, Berni Canani R (2015) Bugs for atopy: the Lactobacillus rhamnosus GG strategy for food allergy prevention and treatment in children. Benefic Microbes 6(2):225–232CrossRefGoogle Scholar
  109. 109.
    Kim H-J, Kim HY, Lee SY, Seo JH, Lee E, Hong SJ (2013) Clinical efficacy and mechanism of probiotics in allergic diseases. Korean J Pediatr 56(9):369–376PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Ouwehand AC (2007) Antiallergic effects of probiotics. J Nutr 137(3):794S–797SPubMedCrossRefPubMedCentralGoogle Scholar
  111. 111.
    Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, Morelli L, Canani RB, Flint HJ, Salminen S, Calder PC, Sanders ME (2014) Expert consensus document: the International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 11(8):506–514PubMedCrossRefPubMedCentralGoogle Scholar
  112. 112.
    Doron S, Snydman DR (2015) Risk and safety of probiotics. Clin Infect Dis 60(suppl_2):S129–S134PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Ruszczyński M, Radzikowski A, Szajewska H (2008) Clinical trial: effectiveness of Lactobacillus rhamnosus (strains E/N, oxy and pen) in the prevention of antibiotic-associated diarrhoea in children. Aliment Pharmacol Ther 28(1):154–161PubMedCrossRefPubMedCentralGoogle Scholar
  114. 114.
    Ramos CL, Thorsen L, Schwan RF, Jespersen L (2013) Strain-specific probiotics properties of Lactobacillus fermentum, Lactobacillus plantarum and Lactobacillus brevis isolates from Brazilian food products. Food Microbiol 36(1):22–29PubMedCrossRefPubMedCentralGoogle Scholar
  115. 115.
    Toh ZQ et al (2012) Probiotic therapy as a novel approach for allergic disease. Front Pharmacol 3:171PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Sanders ME, Akkermans LM, Haller D, Hammerman C, Heimbach J, Hörmannsperger G, Huys G, Levy DD, Lutgendorff F, Mack D, Phothirath P, Solano-Aguilar G, Vaughan E (2010) Safety assessment of probiotics for human use. Gut Microbes 1(3):164–185PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Iannitti T, Palmieri B (2010) Therapeutical use of probiotic formulations in clinical practice. Clin Nutr 29(6):701–725PubMedCrossRefPubMedCentralGoogle Scholar
  118. 118.
    Marteau P (2001) Safety aspects of probiotic products. Näringsforskning 45(1):22–24CrossRefGoogle Scholar
  119. 119.
    Elmer GW (2001) Probiotics: “living drugs”. Am J Health Syst Pharm 58(12):1101–1109PubMedPubMedCentralGoogle Scholar
  120. 120.
    Liong M-T (2008) Safety of probiotics: translocation and infection. Nutr Rev 66(4):192–202PubMedCrossRefPubMedCentralGoogle Scholar
  121. 121.
    West CE, D’Vaz N, Prescott SL (2011) Dietary immunomodulatory factors in the development of immune tolerance. Curr Allergy Asthma Rep 11(4):325–333PubMedCrossRefPubMedCentralGoogle Scholar
  122. 122.
    Calder PC (2009) Polyunsaturated fatty acids and inflammatory processes: new twists in an old tale. Biochimie 91(6):791–795PubMedCrossRefPubMedCentralGoogle Scholar
  123. 123.
    Tan PH, Sagoo P, Chan C, Yates JB, Campbell J, Beutelspacher SC, Foxwell BMJ, Lombardi G, George AJT (2005) Inhibition of NF-kappa B and oxidative pathways in human dendritic cells by antioxidative vitamins generates regulatory T cells. J Immunol 174(12):7633–7644PubMedCrossRefPubMedCentralGoogle Scholar
  124. 124.
    Rochat MK et al (2010) Maternal vitamin D intake during pregnancy increases gene expression of ILT3 and ILT4 in cord blood. Clin Exp Allergy 40(5):786–794PubMedCrossRefPubMedCentralGoogle Scholar
  125. 125.
    Ren C, Zhang Q, Wang G, Ai C, Hu M, Liu X, Tian F, Zhao J, Chen Y, Wang M, Zhang H, Chen W (2014) Modulation of peanut-induced allergic immune responses by oral lactic acid bacteria-based vaccines in mice. Appl Microbiol Biotechnol 98(14):6353–6364PubMedCrossRefPubMedCentralGoogle Scholar
  126. 126.
    Adel-Patient K, Ah-Leung S, Creminon C, Nouaille S, Chatel JM, Langella P, Wal JM (2005) Oral administration of recombinant Lactococcus lactis expressing bovine beta-lactoglobulin partially prevents mice from sensitization. Clin Exp Allergy 35(4):539–546PubMedCrossRefGoogle Scholar
  127. 127.
    Hazebrouck S, Oozeer R, Adel-Patient K, Langella P, Rabot S, Wal JM, Corthier G (2006) Constitutive delivery of bovine beta-lactoglobulin to the digestive tracts of gnotobiotic mice by engineered Lactobacillus casei. Appl Environ Microbiol 72(12):7460–7467PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Huibregtse IL, Snoeck V, de Creus A, Braat H, de Jong EC, van Deventer SJH, Rottiers P (2007) Induction of ovalbumin-specific tolerance by oral administration of Lactococcus lactis secreting ovalbumin. Gastroenterology 133(2):517–528CrossRefGoogle Scholar
  129. 129.
    Cortes-Perez NG (2009) Allergy therapy by intranasal administration with recombinant Lactococcus lactis producing bovine β-lactoglobulin. Int Arch Allergy Immunol 150(1):25–31PubMedCrossRefGoogle Scholar
  130. 130.
    Azevedo M et al (2013) Immunotherapy of allergic diseases using probiotics or recombinant probiotics. J Appl Microbiol 115(2):319–333PubMedCrossRefPubMedCentralGoogle Scholar
  131. 131.
    Anzengruber J, Bublin M, Bönisch E, Janesch B, Tscheppe A, Braun ML, Varga EM, Hafner C, Breiteneder H, Schäffer C (2017) Lactobacillus buchneri S-layer as carrier for an Ara h 2-derived peptide for peanut allergen-specific immunotherapy. Mol Immunol 85:81–88PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Pouwels PH, Leer RJ, Boersma WJ (1996) The potential of Lactobacillus as a carrier for oral immunization: development and preliminary characterization of vector systems for targeted delivery of antigens. J Biotechnol 44(1–3):183–192PubMedCrossRefGoogle Scholar
  133. 133.
    Scudellari M (2017) News feature: cleaning up the hygiene hypothesis. Proc Natl Acad Sci U S A 114(7):1433–1436PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Kliewer KL, Cassin AM, Venter C (2018) Dietary therapy for eosinophilic esophagitis: elimination and reintroduction. Clin Rev Allergy Immunol 55(1):70–87PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Rheumatology/Allergy and Clinical Immunology, School of MedicineThe University of CaliforniaDavisUSA
  2. 2.School of Life SciencesThe Chinese University of Hong KongShatinHong Kong SAR, China
  3. 3.Department of Food Science and Technology, Jinling CollegeNanjing Normal UniversityNanjingChina

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