Lenoir Marion, Del Carmen Silvina, Cortes-Perez Naima G, Lozano-Ojalvo Daniel, Muñoz-Provencio Diego, Chain Florian, Langella Philippe, de Moreno de LeBlanc Alejandra, LeBlanc Jean Guy, Bermúdez-Humarán Luis G
INRA, Commensal and Probiotics-Host Interactions Laboratory, UMR 1319 Micalis, 78350, Jouy-en-Josas, France.
AgroParisTech, UMR1319 Micalis, 78350, Jouy-en-Josas, France.
J Gastroenterol. 2016 Sep;51(9):862-73. doi: 10.1007/s00535-015-1158-9. Epub 2016 Jan 9.
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.
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.
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.
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.
慢性肠道炎症会改变宿主生理机能，并可能导致结直肠癌（CRC）。我们之前报道过干酪乳杆菌BL23益生菌株在不同的肠道炎症小鼠模型中具有有益作用。此外，益生菌对治疗结直肠癌的潜在有益作用也越来越受到关注。因此，我们探究了干酪乳杆菌BL23对结直肠癌是否具有保护作用。
在10周内，每周给小鼠皮下注射1,2-二甲基肼（DMH），并在饮用水中口服给予干酪乳杆菌BL23直至第10周。宏观观察并计数大肠中的多个斑块病变，同时对肠道组织进行组织学分析。最后，将干酪乳杆菌BL23与未处理小鼠的脾细胞共同孵育后，评估T细胞群体和细胞因子的产生，以确定该细菌的免疫调节作用。
我们的结果表明，口服这种益生菌可调节宿主免疫反应，并显著保护小鼠免受DMH诱导的结直肠癌。这种保护作用可能与调节性T细胞向Th17偏向的免疫反应的调节有关，伴随着调节性细胞因子（IL-6、IL-17、IL-10和TGF-β）的表达，如在干酪乳杆菌BL23处理的脾细胞中所示，也与在干酪乳杆菌BL23处理的小鼠体内观察到的结肠中IL-22的表达有关；这表明诱导了一种微调的Th17偏向反应。
我们的结果总体上揭示了干酪乳杆菌BL23治疗结直肠癌的巨大潜力，并为益生菌免疫调节功能的研究开辟了新的前沿领域。
