Abstract
Background
Interventions targeting the gut microbiota for treating food allergy (FA) have been gaining much attention. Although several studies have examined the effects of probiotics, few have verified the effects of prebiotic intervention on FA in humans.
Methods
We conducted a preliminary open-label, parallel-group comparison trial in children diagnosed with severe cow’s milk allergy (CMA) who were instructed to ingest baked milk (BM; bread or cookies) daily. The subjects either received or did not receive the prebiotic 1-kestose (kestose) daily for 6 months. CMA symptoms and the threshold dose for milk protein were evaluated by oral food challenge with heated milk or BM. Blood and fecal samples were also collected for investigations of the antigen-specific immunoglobulin (Ig) E levels and microbiota composition.
Results
Kestose treatment significantly increased the threshold dose for milk protein, and decreased the milk- and casein-specific IgE levels in serum. In those treated with kestose, the abundance of Fusicatenibacter spp. significantly increased in the feces, and a significant inverse correlation was seen between the abundance of Fusicatenibacter spp. and the milk- and casein-specific IgE levels.
Conclusion
Kestose treatment induced some tolerance to milk protein via changes in the gut microbiota composition in children with FA.
Impact
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A 6-month treatment with the prebiotic kestose increased the threshold dose for milk protein, and decreased the serum levels of milk- and casein-specific IgE in children diagnosed with cow’s milk allergy.
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The kestose treatment increased the abundance of Fusicatenibacter spp. in the gut, which was inversely correlated with the antigen-specific IgE levels.
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This is the first study to demonstrate that a prebiotic intervention induced some tolerance to an allergen in children with food allergy.
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Data availability
The datasets generated and/or analyzed during the present study are available from the corresponding author on reasonable request.
References
Sicherer, S. H. & Sampson, H. A. Food allergy: epidemiology, pathogenesis, diagnosis, and treatment. J. Allergy Clin. Immunol. 133, 291–308 (2014).
Ebisawa, M. et al. Japanese guidelines for food allergy 2020. Allergol. Int. 69, 370–386 (2020).
Moneret-Vautrin, D. A. & Kanny, G. Update on threshold doses of food allergens: implications for patients and the food industry. Curr. Opin. Allergy Clin. Immunol. 4, 215–219 (2004).
Inuo, C. et al. Oral immunotherapy using partially hydrolyzed formula for cow’s milk protein allergy: a randomized, controlled trial. Int. Arch. Allergy Immunol. 177, 259–268 (2018).
Niggemann, B. et al. Safety and efficacy of a new extensively hydrolyzed formula for infants with cow’s milk protein allergy. Pediatr. Allergy Immunol. 19, 348–354 (2008).
Upton, J. & Nowak-Wegrzyn, A. The impact of baked egg and baked milk diets on IgE- and non-IgE-mediated allergy. Clin. Rev. Allergy Immunol. 55, 118–138 (2018).
Esmaeilzadeh, H. et al. The effect of baked milk on accelerating unheated cow’s milk tolerance: a control randomized clinical trial. Pediatr. Allergy Immunol. 29, 747–753 (2018).
Goldberg, M. R. et al. Efficacy of baked milk oral immunotherapy in baked milk-reactive allergic patients. J. Allergy Clin. Immunol. 136, 1601–1606 (2015).
Dunlop, J. H., Keet, C. A., Mudd, K. & Wood, R. A. Long-term follow-up after baked milk introduction. J. Allergy Clin. Immunol. Pract. 6, 1699–1704 (2018).
Tanaka, M. et al. Signatures in the gut microbiota of Japanese infants who developed food allergies in early childhood. FEMS Microbiol. Ecol. 93, fix099 (2017).
Berni Canani, R. et al. Gut microbiota composition and butyrate production in children affected by non-IgE-mediated cow’s milk allergy. Sci. Rep. 8, 12500 (2018).
Savage, J. H. et al. A prospective microbiome-wide association study of food sensitization and food allergy in early childhood. Allergy 73, 145–152 (2018).
Berni Canani, R. et al. Effect of Lactobacillus GG on tolerance acquisition in infants with cow’s milk allergy: a randomized trial. J. Allergy Clin. Immunol. 129, 580–582.e5825 (2012).
Berni Canani, R. et al. Formula selection for management of children with cow’s milk allergy influences the rate of acquisition of tolerance: a prospective multicenter study. J. Pediatr. 163, 771–777.e1 (2013).
Cukrowska, B. et al. The effectiveness of probiotic Lactobacillus rhamnosus and Lactobacillus casei strains in children with atopic dermatitis and cow’s milk protein allergy: a multicenter, randomized, double blind, placebo controlled study. Nutrients 13, 1169 (2021).
Schouten, B. et al. Oligosaccharide-induced whey-specific CD25(+) regulatory T-cells are involved in the suppression of cow milk allergy in mice. J. Nutr. 140, 835–841 (2010).
Shibata, R. et al. Clinical effects of kestose, a prebiotic oligosaccharide, on the treatment of atopic dermatitis in infants. Clin. Exp. Allergy 39, 1397–1403 (2009).
Matsumoto, K., Mori, R., Miyazaki, C., Ohya, Y. & Saito, H. Are both early egg introduction and eczema treatment necessary for primary prevention of egg allergy? J. Allergy Clin. Immunol. 141, 1997–2001.e3 (2018).
Hisada, T., Endoh, K. & Kuriki, K. Inter- and intra-individual variations in seasonal and daily stabilities of the human gut microbiota in Japanese. Arch. Microbiol. 197, 919–934 (2015).
Tochio, T. et al. An alteration in the cecal microbiota composition by feeding of 1-kestose results in a marked increase in the cecal butyrate content in rats. PLoS One 11, e0166850 (2016).
Diez, M., Hornick, J. L., Baldwin, P. & Istasse, L. Influence of a blend of fructo-oligosaccharides and sugar beet fiber on nutrient digestibility and plasma metabolite concentrations in healthy beagles. Am. J. Vet. Res. 58, 1238–1242 (1997).
Campbell, J. et al. Selected fructooligosaccharide (1-kestose, nystose, and 1F-β-fructofuranosylnystose) composition of foods and feeds. J. Agric. Food Chem. 45, 3076–3082 (1997).
Endo, A., Nakamura, S., Konishi, K., Nakagawa, J. & Tochio, T. Variations in prebiotic oligosaccharide fermentation by intestinal lactic acid bacteria. Int. J. Food Sci. Nutr. 67, 125–132 (2016).
Ose, R. et al. The ability of human intestinal anaerobes to metabolize different oligosaccharides: novel means for microbiota modulation? Anaerobe 51, 110–119 (2018).
Koga, Y. et al. Age-associated effect of kestose on Faecalibacterium prausnitzii and symptoms in the atopic dermatitis infants. Pediatr. Res. 80, 844–851 (2018).
Kadota, Y., Koga, Y., Tochio, T. & Shibata, R. Subjective evaluation using Patient‐Oriented Eczema Measure (POEM) for the clinical effect of 1-kestose on atopic dermatitis in children: a pilot study. Int. J. Probiotics Prebiotics 17, 47–52 (2022).
Coombs, P. R. & Gell, P. G. Classification of Allergic Reactions Responsible for Clinical Hypersensitivity and Disease: Clinical Aspects of Immunology (Oxford University Press, Oxford, 1968).
Wood, R. A. et al. The natural history of milk allergy in an observational cohort. J. Allergy Clin. Immunol. 131, 805–812 (2013).
Takada, T., Kurakawa, T., Tsuji, H. & Nomoto, K. Fusicatenibacter saccharivorans gen. nov., sp. nov., isolated from human faeces. Int. J. Syst. Evol. Microbiol 63, 3691–3696 (2013).
Takeshita, K. et al. Single species of clostridium subcluster XIVa decreased in ulcerative colitis patients. Inflamm. Bowel Dis. 22, 2802–2810 (2016).
Berni Canani, R. et al. Lactobacillus rhamnosus GG-supplemented formula expands butyrate-producing bacterial strains in food allergic infants. ISME J. 10, 742–750 (2016).
Acknowledgements
This study was supported by B Food Science Co., Ltd., and the Department of Pediatrics of the National Hospital Organization Fukuoka National Hospital. We thank all patients and parents who participated in this study for sharing their time and perspectives.
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Contributions
R.S. designed the trial. R.S. and Y.M. recruited patients, and obtained data and samples. Y. Kadota analyzed the samples, and obtained data. Y. Koga, M.T., and T.T. helped with the analysis and discussion. Y. Kadota wrote the manuscript. Y. Koga and R.S. revised the manuscript for important intellectual content.
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Competing interests
Y. Kadota and M.T. are employees of B Food Science Co. Ltd, which was the producer of the 1-kestose used in this study. The remaining authors declare no conflicts of interest. There are no conflicts to declare relating to consultancies, patents or products in development, or marketed products with regard to this work.
Ethics approval and consent to participate
This study was designed in adherence with the principles laid out in the Declaration of Helsinki for experiments involving human beings. The study was approved by the ethics committee of the National Hospital Organization Fukuoka National Hospital, and is registered in the UMIN Clinical Trials Registry (UMIN000037227). Written informed consent was obtained from the guardians of all subjects after the subjects and their guardians received an explanation about the study.
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Shibata, R., Koga, Y., Takahashi, M. et al. In children with cow’s milk allergy, 1-kestose affects the gut microbiota and reaction threshold. Pediatr Res 94, 1067–1074 (2023). https://doi.org/10.1038/s41390-023-02557-7
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DOI: https://doi.org/10.1038/s41390-023-02557-7