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Bifidobacteria modulate immune response in pediatric patients with cow’s milk protein allergy



In children with an allergy to cow’s milk proteins (CMA), the altered composition of intestinal microbiota influences the immune tolerance to milk proteins (CMP). This study aims to investigate the effect of probiotics on the phenotype and activation status of peripheral basophils and lymphocytes in a pediatric CMA cohort.


CMA children underwent 45 days of treatment with Bifidobacteria. The basophil degranulation and the immune phenotype of B cells, T helper cells, and regulatory T cells were analyzed in peripheral blood at diagnosis (T0), after a 45-day probiotic treatment (T1), and 45 days after the probiotic wash-out (T2).


We observed in probiotic-treated CMA patients a decrease in naive T lymphocytes. Among the CD3+ cell subsets, both naive and activated CD4+ cells resulted markedly reduced after taking probiotics, with the lowest percentages at T2. A decreased basophil degranulation was observed in response to all analyzed CMP at T1 compared to T0.


The probiotic treatment resulted in a decrease of circulating naive and activated CD4+ T cells, as well as degranulating basophils. These data suggest that the Bifidobacteria could have a beneficial effect in the modulation of oral tolerance to CMP.

Trial registration

ISRCTN69069358. URL of registration:


  • Probiotic treatment with Bifidobacteria induces a reduction of both naive and activated circulating CD4+ T cells in pediatric patients with cow’s milk allergy (CMA).

  • The probiotic supplementation induces a decreased basophil degranulation.

  • The immunological tolerance persists even after 45 days of the probiotic wash-out.

  • Bifidobacteria in vivo supplementation down-modulates the activation of innate and adaptive immunity in pediatric patients with cow’s milk allergy.

  • Bifidobacteria contribute to the development of immune tolerance in CMA patients.

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Fig. 1: Cell population percentages analyzed by flow cytometry.
Fig. 2: The effect of probiotic treatment on the frequency of circulating T and B cell subsets.
Fig. 3: Effect of probiotic treatment on the percentage of degranulating basophils in response to cow’s milk proteins.

Data availability

The datasets generated during and/or analyzed during the study will be available upon request to the authors.


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Authors and Affiliations



C.S. and A.V. contributed to the conception and design of the study, sample collection, analysis and interpretation of data, and drafted the article; F.P. performed the BAT experiments; F.G. contributed to sample collection and performed BAT experiments. P.D. performed the statistical and correlation analysis; S.V., T.M., and F.O. contributed to sample collection and analysis; M.M.d.G. contributed to the conception, design, and intellectual content of the study; G.M. and C.G. contributed to the conception, design and intellectual content of the study, revised the data, and drafted the article.

Corresponding author

Correspondence to Caterina Strisciuglio.

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Competing interests

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethics approval and consent to participate

The study was approved by the Institutional Review Board of the University of Campania “Luigi Vanvitelli” (registration number 07/2016). Written informed consent for participation in the study and publishing of individual patient data were obtained from the parents of all children.

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Strisciuglio, C., Vitale, A., Perna, F. et al. Bifidobacteria modulate immune response in pediatric patients with cow’s milk protein allergy. Pediatr Res (2023).

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