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  • Clinical Research Article
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In children with cow’s milk allergy, 1-kestose affects the gut microbiota and reaction threshold

Pediatric Research volume 94, pages 1067–1074 (2023)Cite this article

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

  • 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.

  • The kestose treatment increased the abundance of Fusicatenibacter spp. in the gut, which was inversely correlated with the antigen-specific IgE levels.

  • 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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Fig. 1: Study design.
Fig. 2: Changes in the threshold level for milk protein and the amounts of milk- and casein-specific IgE in serum during the study period.
Fig. 3: Changes in the α-diversity of the gut microbiota during the study period.
Fig. 4: Correlation analysis between the intestinal bacterial composition and the clinical and laboratory parameters associated with food allergy.
Fig. 5: Changes in the concentration of short-chain fatty acids during the study period.

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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.

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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.

Author information

Authors and Affiliations

  1. Department of Pediatrics, National Hospital Organization, Fukuoka National Hospital, Fukuoka, Japan

    Rumiko Shibata & Youko Murakami

  2. Department of Gastroenterology, Tokai University School of Medicine, Isehara, Japan

    Yasuhiro Koga

  3. Research and Development Center, B Food Science Co., Ltd., Chita, Japan

    Mayuko Takahashi & Yoshihiro Kadota

  4. Department of Gastroenterology and Hepatology, Fujita Health University, Toyoake, Japan

    Takumi Tochio

Authors
  1. Rumiko Shibata
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  2. Yasuhiro Koga
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  4. Youko Murakami
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  5. Takumi Tochio
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  6. Yoshihiro Kadota
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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.

Corresponding author

Correspondence to Yoshihiro Kadota.

Ethics declarations

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

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