RETRACTED ARTICLE: Lactobacillus casei BL23 regulates T reg and Th17 T-cell populations and reduces DMH-associated color
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ORIGINAL ARTICLE—ALIMENTARY TRACT
Lactobacillus casei BL23 regulates Treg and Th17 T-cell populations and reduces DMH-associated colorectal cancer Marion Lenoir1,2 • Silvina del Carmen3 • Naima G. Cortes-Perez4,5 • Daniel Lozano-Ojalvo4,5,6 • Diego Mun˜oz-Provencio1,2 • Florian Chain1,2 • Philippe Langella1,2 • Alejandra de Moreno de LeBlanc3 • Jean Guy LeBlanc3 Luis G. Bermu´dez-Humara´n1,2
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Received: 15 September 2015 / Accepted: 19 December 2015 Ó Japanese Society of Gastroenterology 2016
Abstract 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 1,2dimethylhydrazine (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. Marion Lenoir, Silvina del Carmen and Alejandra de Moreno de LeBlanc have contributed equally to this work. & Jean Guy LeBlanc [email protected] & Luis G. Bermu´dez-Humara´n [email protected] 1
INRA, Commensal and Probiotics-Host Interactions Laboratory, UMR 1319 Micalis, 78350 Jouy-en-Josas, France
2
AgroParisTech, UMR1319 Micalis, 78350 Jouy-en-Josas, France
3
Centro de Referencia para Lactobacilos (CERELACONICET), T4000ILC San Miguel de Tucuma´n, Argentina
4
INRA, UR496 Unite´ d’Immuno-Allergie Alimentaire, Jouy-en-Josas, France
5
CEA, IBiTecS, Service de Pharmacologie et d’Immunoanalyse, Gif-sur-Yvette, France
6
Present Address: Instituto de Investigacio´n en Ciencias de la Alimentacio´n (CIAL, CSIC-UAM), Madrid, Spain
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 immunomodulatory 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-b), as demonstrated in L. casei BL23-treated splenocytes, but also with the colonic expression of IL-22 observed in vivo on L. casei BL23treated mice; suggesting the induction of a fine-tune Th17biased 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. Keywords Probiotics Lactic acid bacteria Lactobacillus casei BL23 Colo
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