Lactobacillus casei BL23 regulates Treg and Th17 T-cell populations and reduces DMH-associated colorectal cancer

Background: Chronic intestinal inflammation alters host physiology and could lead to colorectal cancer (CRC). We have previously reported beneficial effects of the probiotic strain of Lactobacillus casei BL23 in different murine models of intestinal inflammation. In addition, there is an emerging interest on the potential beneficial effects of probiotics to treat CRC. We thus explored whether L. casei BL23 displays protective effects on CRC. Methods: Mice were subcutaneously injected with 1,2-dimethylhydrazine (DMH) weekly during 10 weeks and orally administered with L. casei BL23 in the drinking water until the 10th week. Multiple plaque lesions in the large intestine were observed macroscopically and counted and intestinal tissues were also histologically analyzed. Finally, T-cell populations and cytokine production were evaluated after co-incubation of L. casei BL23 with spleen cells from non-treated mice to determine the immuno-modulatory effects of this bacterium. Results: Our results show that oral treatment with this probiotic bacterium modulates host immune responses and significantly protect mice against DMH-induced CRC. This protection may be associated with the modulation of regulatory T-cells towards a Th17-biased immune response accompanied by the expression of regulatory cytokines (IL-6, IL-17, IL-10 and TGF-β), as demonstrated in L. casei BL23-treated splenocytes, but also with the colonic expression of IL-22 observed in vivo on L. casei BL23-treated mice; suggesting the induction of a fine-tune Th17-biased response. Conclusions: Altogether our results reveal the high potential of L. casei BL23 to treat CRC and opens new frontiers for the study of immunomodulatory functions of probiotics. Fil: Lenoir, Marion. Institut National de la Recherche Agronomique; Francia. AgroParisTech; Francia Fil: del Carmen, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina Fil: Cortes Perez, Naima G.. Institut National de la Recherche Agronomique; Francia Fil: Lozano Ojalvo, Daniel. Institut National de la Recherche Agronomique; Francia. Service de Pharmacologie et d’Immunoanalyse. CEA, IBiTecS; Francia. Consejo Superior de Investigaciones Científicas. Instituto de Investigación en Ciencias de la Alimentación; España Fil: Muñoz Provencio, Diego. Institut National de la Recherche Agronomique; Francia Fil: Chain, Florian. Institut National de la Recherche Agronomique; Francia Fil: Langella, Philippe. Institut National de la Recherche Agronomique; Francia Fil: de Moreno, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina Fil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucuman. Centro de Referencia Para Lactobacilos; Argentina Fil: Bermudez Humaran, Luis G.. Institut National de la Recherche Agronomique; Francia