Probiotics in Crohn disease: selecting strains able to trigger Paneth cells-derived antimicrobial response and downregulate inflammatory response.

RATIONALE: Paneth cells from Crohn's disease patients showed impaired secretion of antimicrobial peptides, which may contribute to an inappropriate mucosal immune response. Herein, we identified novel anti-inflammatory probiotic strains that are able to modulate the functionality of Paneth cells. METHODS: The capacity of selected probiotic strains to induce defensin expression was tested in vitro using the murine epithelial cell line mICcl2. Induction of activation markers (CD40, CD80, CD86, MHCII) on bone-marrow dendritic cells (BMDC) after 24 hrs of coculture with bacterial strains was followed by flow cytometry. The potential of probiotic strains to promote either Th17 or Tregs was evaluated by coculture of naive CD4⁺CD25^- cells with probiotic-primed dendritic cells. Mouse model of Citrobacter rodentium infection was used for testing the capacity of probiotic strains to decrease inflammation in vivo. RESULTS: Strain and time dependent differences in the gene expression of defensins in mICcl2 were observed. Some strains E. coli, L. Reuteri or L. acidophillus were good inducers of defensin expression. L. acidophillus strains were the most potent inducers of activation markers on dendritic cells and the best inducer of IL-17 after six-day coculture of primed BMDC and naive CD4 cells, while L. reuteri and L. paracasei strains were the best inducers of Tregs. The aforementionned probiotic strains induced the colonic expression of several defensins in vivo and showed anti-inflammatory effects in response to C. rodentium. In conclusion, we have identified several promising probiotic strains for the treatment of Crohn's disease. This work was supported by the ANR project BIOpaneX.