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Probiotic Propionibacterium freudenreichii requires SlpB protein to mitigate mucositis induced by chemotherapy

  • 2019-12-31
  • Oncotarget 10(68)
    • F. L. R. do Carmo
    • Houem Rabah
    • B. F. Cordeiro
    • S. H. da Silva
    • R. M. Pessoa
    • S. O. Fernandes
    • V. Cardoso
    • V. Gagnaire
    • M. Deplanche
    • Bruna Savassi
    • Alessandra Figueiroa
    • E. Oliveira
    • Caio Fonseca
    • Maria Izabel Alves Queiroz
    • N. M. Rodrigues
    • S. Sandes
    • Á. Nunes
    • Luísa Lemos
    • J. Alves
    • A. C. Faria
    • Ê. Ferreira
    • Y. Le Loir
    • G. Jan
    • V. Azevedo

Abstract

Propionibacterium freudenreichii CIRM-BIA 129 (P. freudenreichii wild type, WT) is a probiotic bacterium, which exerts immunomodulatory effects. This strain possesses extractable surface proteins, including SlpB, which are involved in anti-inflammatory effect and in adhesion to epithelial cells. We decided to investigate the impact of slpB gene mutation on immunomodulation in vitro and in vivo. In an in vitro assay, P. freudenreichii WT reduced expression of IL-8 (p<0.0001) and TNF-α (p<0.0001) cytokines in LPS-stimulated HT-29 cells. P. freudenreichii Δ_slpB_, lacking the SlpB protein, failed to do so. Subsequently, both strains were investigated in vivo in a 5-FU-induced mucositis mice model. Mucositis is a common side effect of cytotoxic chemotherapy with 5-FU, characterized by mucosal injury, inflammation, diarrhea, and weight loss. The WT strain prevented weight loss, reduced inflammation and consequently histopathological scores. Furthermore, it regulated key markers, including Claudin-1 (cld1, p<0.0005) and IL-17a (Il17a, p<0.0001) genes, as well as IL-12 (p<0.0001) and IL-1β (p<0.0429) cytokines levels. Mutant strain displayed opposite regulatory effect on cld1 expression and on IL-12 levels. This work emphasizes the importance of SlpB in P. freudenreichii ability to reduce mucositis inflammation. It opens perspectives for the development of probiotic products to decrease side effects of chemotherapy using GRAS bacteria with immunomodulatory surface protein properties.

Keywords: immunomodulation; inflammation; mucositis; probiotic; surface protein.

Research Insights

SupplementHealth OutcomeEffect TypeEffect Size
Propionibacterium freudenreichii MAK10P23FEnhanced Anti-inflammatory Cytokine LevelsBeneficial
Moderate
Propionibacterium freudenreichii MAK10P23FMitigated Chemotherapy-Induced MucositisBeneficial
Large
Propionibacterium freudenreichii MAK10P23FReduced Pro-inflammatory Cytokine LevelsBeneficial
Large
Propionibacterium freudenreichii MAK10P23FRegulated Intestinal Barrier FunctionBeneficial
Moderate
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