Digestive Diseases and Sciences

, Volume 60, Issue 11, pp 3386–3392 | Cite as

Administration of Bifidobacterium breve Decreases the Production of TNF-α in Children with Celiac Disease

  • Martina Klemenak
  • Jernej Dolinšek
  • Tomaž Langerholc
  • Diana Di Gioia
  • Dušanka Mičetić-Turk
Original Article



Increasing evidence suggests that not only genetics, but also environmental factors like gut microbiota dysbiosis play an important role in the pathogenesis of celiac disease (CD).


The aim of our study was to investigate the effect of two probiotic strains Bifidobacterium breve BR03 and B. breve B632 on serum production of anti-inflammatory cytokine interleukin 10 (IL-10) and pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) in children with CD.


The study was a double-blinded, placebo-controlled trial that included 49 children with CD on gluten-free diet (GFD) randomized into two groups and 18 healthy children in the control group. The first group (24 children with CD) daily received B. breve BR03 and B632 (2 × 109 colony-forming units) and the second group (25 children with CD) received placebo for 3 months.


TNF-α levels were significantly decreased in the first group after receiving B. breve for 3 months. On follow-up, 3 months after receiving probiotics, TNF-α levels increased again. Children with CD who were on GFD for less than 1 year showed similar baseline TNF-α levels as children who were on GFD for more than 1 year. IL-10 levels were in all groups of patients below detection level.


Probiotic intervention with B. breve strains has shown a positive effect on decreasing the production of pro-inflammatory cytokine TNF-α in children with CD on GFD.


Celiac disease Bifidobacterium breve Cytokines TNF-α Children 



We are grateful to Evgenija Homšak and Mateja Svetej for laboratory assistance, nurses in pediatric hospital for assistance in the clinical management of patients and to Mario Gorenjak for statistical analysis. We are indebted to Maja Šikić Pogačar for critical evaluation of the manuscript and editing of the text. We are also grateful to Probiotical S.p.A. (Novara, Italy) for providing the intervention products free of charge and to parents of children with celiac disease and healthy children for cooperation in the research.

Conflict of interest

This study was supported by the research programme group “Bio-psycho-social model of quality of life” P3-0036. The intervention products were produced and provided free of charge by Probiotical S.p.A (Italy). The authors declare no conflicts of interest.

Ethical standard

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Martina Klemenak
    • 1
  • Jernej Dolinšek
    • 1
  • Tomaž Langerholc
    • 2
  • Diana Di Gioia
    • 3
  • Dušanka Mičetić-Turk
    • 4
  1. 1.Department of PaediatricsUniversity Clinical Center MariborMariborSlovenia
  2. 2.Department of Microbiology, Biochemistry, Molecular Biology and Biotechnology, Faculty of Agriculture and Life SciencesUniversity of MariborHočeSlovenia
  3. 3.Department of Agricultural SciencesUniversity of BolognaBolognaItaly
  4. 4.Department of Paediatrics, Faculty of MedicineUniversity of MariborMariborSlovenia

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