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 ΔslpB, 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.