Background: Food allergy research is hampered by a lack of animal models that consistently mimic human food allergic responses. Laboratory mice are generally fed grain-based chow made with large amounts of soybeans rich in immunomodulatory isoflavones. We tested the role of dietary soy components in the induction of food allergic responses in the BALB/c mouse strain, which is known to be resistant to anaphylaxis when orally challenged by food allergens. Methods: Mice were fed a soy-free diet for 2 generations. After weaning, mice were maintained on the same diet or fed a diet containing soy isoflavones, i.e. genistein and daidzein, followed by weekly oral sensitizations with crude peanut extract plus cholera toxin and finally challenged at week 7. The anaphylactic symptoms, body temperature, peanut-specific antibodies and mast cell degranulation were assessed. Results: Soy-free diet mice showed significantly higher anaphylactic symptom scores and mast cell degranulation after challenge and higher peanut-specific antibody levels than mice fed regular chow. Introduction of a regular soy diet or an isoflavone diet to soy-free diet mice significantly suppressed the allergic reactions compared to the soy-free diet. Conclusion: Rodent diet is an important variable and needs to be taken into consideration when designing experiments involving animal models. Our results indicate that elimination of soy components from the diet enhances peanut sensitization in BALB/c mice. In addition to serving as a valuable tool to mimic human food allergy, the dietary influence on the immune response could have far-reaching consequences in research involving animal models.

Brown NM, Setchell KD: Animal models impacted by phytoestrogens in commercial chow: implications for pathways influenced by hormones. Lab Invest 2001;81:735-747.
Degen GH, Janning P, Diel P, Bolt HM: Estrogenic isoflavones in rodent diets. Toxicol Lett 2002;128:145-157.
Jensen MN, Ritskes-Hoitinga M: How isoflavone levels in common rodent diets can interfere with the value of animal models and with experimental results. Lab Anim 2007;41:1-18.
Ruhlen RL, Taylor JA, Mao J, Kirkpatrick J, Welshons WV, vom Saal FS: Choice of animal feed can alter fetal steroid levels and mask developmental effects of endocrine disrupting chemicals. J Dev Orig Health Dis 2011;2:36-48.
Thigpen JE, Setchell KD, Ahlmark KB, Locklear J, Spahr T, Caviness GF, Goelz MF, Haseman JK, Newbold RR, Forsythe DB: Phytoestrogen content of purified, open- and closed-formula laboratory animal diets. Lab Anim Sci 1999;49:530-536.
Masilamani M, Wei J, Sampson HA: Regulation of the immune response by soybean isoflavones. Immunol Res 2012;54:95-110.
Heindel JJ, vom Saal FS: Meeting report: batch-to-batch variability in estrogenic activity in commercial animal diets - importance and approaches for laboratory animal research. Environ Health Perspect 2008;116:389-393.
Smit JJ, Willemsen K, Hassing I, Fiechter D, Storm G, van Bloois L, Leusen JHW, Pennings M, Zaiss D, Pieters RHH: Contribution of classic and alternative effector pathways in peanut-induced anaphylactic responses. PLoS One 2011;6:e28917.
Morafo V, Srivastava K, Huang C-K, Kleiner G, Lee S-Y, Sampson HA, Li X-M: Genetic susceptibility to food allergy is linked to differential TH2-TH1 responses in C3H/HeJ and BALB/c mice. J Allergy Clin Immunol 2003;111:1122-1128.
Masilamani M, Wei J, Bhatt S, Paul M, Yakir S, Sampson HA: Soybean isoflavones regulate dendritic cell function and suppress allergic sensitization to peanut. J Allergy Clin Immunol 2011;128:1242-1250.
Li XM, Serebrisky D, Lee SY, Huang CK, Bardina L, Schofield BH, Stanley JS, Burks AW, Bannon GA, Sampson HA: A murine model of peanut anaphylaxis: T- and B-cell responses to a major peanut allergen mimic human responses. J Allergy Clin Immunol 2000;106:150-158.
Bublin M, Breiteneder H: Developing therapies for peanut allergy. Int Arch Allergy Immunol 2014;165:179-194.
Wei J, Bhatt S, Chang LM, Sampson HA, Masilamani M: Isoflavones, genistein and daidzein, regulate mucosal immune response by suppressing dendritic cell function. PLoS One 2012;7:e47979.
Masilamani M, Commins S, Shreffler W: Determinants of food allergy. Immunol Allergy Clin North Am 2012;32:11-33.
Fritz WA, Coward L, Wang J, Lamartiniere CA: Dietary genistein: perinatal mammary cancer prevention, bioavailability and toxicity testing in the rat. Carcinogenesis 1998;19:2151-2158.
Doerge DR, Churchwell MI, Chang HC, Newbold RR, Delclos KB: Placental transfer of the soy isoflavone genistein following dietary and gavage administration to Sprague Dawley rats. Reprod Toxicol 2001;15:105-110.
Song Y, Liu C, Hui Y, Srivastava K, Zhou Z, Chen J, Miller RL, Finkelman FD, Li XM: Maternal allergy increases susceptibility to offspring allergy in association with TH2-biased epigenetic alterations in a mouse model of peanut allergy. J Allergy Clin Immunol 2014;134:1339-1345.
Day JK, Bauer AM, DesBordes C, Zhuang Y, Kim BE, Newton LG, Nehra V, Forsee KM, MacDonald RS, Besch-Williford C, Huang TH, Lubahn DB: Genistein alters methylation patterns in mice. J Nutr 2002;132:2419S-2423S.
Xie Q, Bai Q, Zou L-Y, Zhang Q-Y, Zhou Y, Chang H, Yi L, Zhu J-D, Mi M-T: Genistein inhibits DNA methylation and increases expression of tumor suppressor genes in human breast cancer cells. Genes Chromosomes Cancer 2014;53:422-431.
Sordillo JE, Lange NE, Tarantini L, Bollati V, Zanobetti A, Sparrow D, Vokonas P, Schwartz J, Baccarelli A, Demeo D, Litonjua AA: Allergen sensitization is associated with increased DNA methylation in older men. Int Arch Allergy Immunol 2013;161:37-43.
Liu J, Ballaney M, Al-alem U, Quan C, Jin X, Perera F, Chen LC, Miller RL: Combined inhaled diesel exhaust particles and allergen exposure alter methylation of T helper genes and IgE production in vivo. Toxicol Sci 2008;102:76-81.
Berin MC, Masilamani M: Experimental approaches to the study of food allergy; in Metcalfe DD, Sampson HA, Simon RA (eds): Food Allergy: Adverse Reactions to Foods and Food Additives. Oxford, Blackwell Publishing, 2012.
Day AJ, Canada FJ, Diaz JC, Kroon PA, McLauchlan R, Faulds CB, Plumb GW, Morgan MR, Williamson G: Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase. FEBS Lett 2000;468:166-170.
Xu X, Harris KS, Wang H-J, Murphy PA, Hendrich S: Bioavailability of soybean isoflavones depends upon gut microflora in women. J Nutr 1995;125:2307-2315.
Souzeau E, Bélanger S, Picard S, Deschepper CF: Dietary isoflavones during pregnancy and lactation provide cardioprotection to offspring rats in adulthood. Am J Physiol Heart Circ Physiol 2005;289:H715-H721.
Westmark CJ, Westmark PR, Malter JS: Soy-based diet exacerbates seizures in mouse models of neurological disease. J Alzheimer Dis 2013;33:797-805.
Harb H, Renz H: Update on epigenetics in allergic disease. J Allergy Clin Immunol 2015;135:15-24.
Niedzwiecki M, Zhu H, Corson L, Grunig G, Factor PH, Chu S, Jiang H, Miller RL: Prenatal exposure to allergen, DNA methylation, and allergy in grandoffspring mice. Allergy 2012;67:904-910.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.