Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Gastroenterology
Published in: Journal of Gastroenterology 9/2016

01-09-2016 | Original Article—Alimentary Tract

RETRACTED ARTICLE: Lactobacillus casei BL23 regulates Treg and Th17 T-cell populations and reduces DMH-associated colorectal cancer

Authors: Marion Lenoir, Silvina del Carmen, Naima G. Cortes-Perez, Daniel Lozano-Ojalvo, Diego Muñoz-Provencio, Florian Chain, Philippe Langella, Alejandra de Moreno de LeBlanc, Jean Guy LeBlanc, Luis G. Bermúdez-Humarán

Published in: Journal of Gastroenterology | Issue 9/2016

Login to get access

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 1,2-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.
Literature
1.
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11–30.PubMed
2.
Viaud S, Saccheri F, Mignot G, Yamazaki T, Daillere R, Hannani D, et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science. 2013;342(6161):971–6.PubMedPubMedCentral
3.
Uccello M, Malaguarnera G, Basile F, D’Agata V, Malaguarnera M, Bertino G, et al. Potential role of probiotics on colorectal cancer prevention. BMC Surg. 2012;12(Suppl 1):S35.PubMedPubMedCentral
4.
Kahouli I, Tomaro-Duchesneau C, Prakash S. Probiotics in colorectal cancer (CRC) with emphasis on mechanisms of action and current perspectives. J Med Microbiol. 2013;62(Pt 8):1107–23.PubMed
5.
6.
Bernardeau M, Vernoux JP, Henri-Dubernet S, Gueguen M. Safety assessment of dairy microorganisms: the Lactobacillus genus. Int J Food Microbiol. 2008;126(3):278–85.PubMed
7.
Madsen KL, Doyle JS, Jewell LD, Tavernini MM, Fedorak RN. Lactobacillus species prevents colitis in interleukin 10 gene-deficient mice. Gastroenterology. 1999;116(5):1107–14.PubMed
8.
Khazaie K, Zadeh M, Khan MW, Bere P, Gounari F, Dennis K, et al. Abating colon cancer polyposis by Lactobacillus acidophilus deficient in lipoteichoic acid. Proc Natl Acad Sci USA. 2012;109(26):10462–7.PubMed
9.
Kato I, Endo K, Yokokura T. Effects of oral-administration of Lactobacillus casei on antitumor responses induced by tumor resection in mice. Int J Immunopharmacol. 1994;16(1):29–36.PubMed
10.
Aragon F, Carino S, Perdigon G, de Moreno de LeBlanc A. Inhibition of growth and metastasis of breast cancer in mice by milk fermented with Lactobacillus casei CRL 431. J Immunother. 2015;38(5):185–96.PubMed
11.
Hu J, Wang C, Ye L, Yang W, Huang H, Meng F, et al. Anti-tumour immune effect of oral administration of Lactobacillus plantarum to CT26 tumour-bearing mice. J Biosci. 2015;40(2):269–79.PubMed
12.
Aragon F, Carino S, Perdigon G, de Moreno de LeBlanc A. The administration of milk fermented by the probiotic Lactobacillus casei CRL 431 exerts an immunomodulatory effect against a breast tumour in a mouse model. Immunobiology. 2014;219(6):457–64.PubMed
13.
Martin R, Miquel S, Ulmer J, Kechaou N, Langella P, Bermudez-Humaran LG. Role of commensal and probiotic bacteria in human health: a focus on inflammatory bowel disease. Microb Cell Fact. 2013;12:71.PubMedPubMedCentral
14.
de Moreno de LeBlanc A, LeBlanc JG. Effect of probiotic administration on the intestinal microbiota, current knowledge and potential applications. World J Gastroenterol. 2014;20(44):16518–28.PubMedPubMedCentral
15.
O’Mahony L, Feeney M, O’Halloran S, Murphy L, Kiely B, Fitzgibbon J, et al. Probiotic impact on microbial flora, inflammation and tumour development in IL-10 knockout mice. Aliment Pharmacol Ther. 2001;15(8):1219–25.PubMed
16.
Lankaputhra WE, Shah NP. Antimutagenic properties of probiotic bacteria and of organic acids. Mutat Res. 1998;397(2):169–82.PubMed
17.
Reddy BS. Prevention of colon cancer by pre- and probiotics: evidence from laboratory studies. Br J Nutr. 1998;80(4):S219–23.PubMed
18.
Brady LJ, Gallaher DD, Busta FF. The role of probiotic cultures in the prevention of colon cancer. J Nutr. 2000;130(2S Suppl):410S–4S.PubMed
19.
Burns AJ, Rowland IR. Anti-carcinogenicity of probiotics and prebiotics. Curr Issues intest Microbiol. 2000;1(1):13–24.PubMed
20.
de Moreno de LeBlanc A, Perdigon G. The application of probiotic fermented milks in cancer and intestinal inflammation. Proc Nutr Soc. 2010;69(3):421–8.PubMed
21.
Reddy BS, Rivenson A. Inhibitory effect of Bifidobacterium longum on colon, mammary, and liver carcinogenesis induced by 2-amino-3-methylimidazo[4,5-f]quinoline, a food mutagen. Cancer Res. 1993;53(17):3914–8.PubMed
22.
Hirayama K, Rafter J. The role of probiotic bacteria in cancer prevention. Microbes Infect. 2000;2(6):681–6.PubMed
23.
Commane D, Hughes R, Shortt C, Rowland I. The potential mechanisms involved in the anti-carcinogenic action of probiotics. Mutat Res. 2005;591(1–2):276–89.PubMed
24.
Rochat T, Bermudez-Humaran L, Gratadoux JJ, Fourage C, Hoebler C, Corthier G, et al. Anti-inflammatory effects of Lactobacillus casei BL23 producing or not a manganese-dependant catalase on DSS-induced colitis in mice. Microb Cell Fact. 2007;6:22.PubMedPubMedCentral
25.
de Moreno de LeBlanc A, LeBlanc JG, Perdigon G, Miyoshi A, Langella P, Azevedo V, et al. Oral administration of a catalase-producing Lactococcus lactis can prevent a chemically induced colon cancer in mice. J Med Microbiol. 2008;57(1):100–5.PubMed
26.
Ribelles P, Benbouziane B, Langella P, Suarez JE, Bermudez-Humaran LG. Protection against human papillomavirus type 16-induced tumors in mice using non-genetically modified lactic acid bacteria displaying E7 antigen at its surface. Appl Microbiol Biotechnol. 2013;97(3):1231–9.PubMed
27.
Maze A, Boel G, Zuniga M, Bourand A, Loux V, Yebra MJ, et al. Complete genome sequence of the probiotic Lactobacillus casei strain BL23. J Bacteriol. 2010;192(10):2647–8.PubMedPubMedCentral
28.
Gasson MJ. Plasmid complements of Streptococcus lactis NCDO 712 and other lactic streptococci after protoplast-induced curing. J Bacteriol. 1983;154(1):1–9.PubMedPubMedCentral
29.
Bermudez-Humaran LG, Cortes-Perez NG, Lefevre F, Guimaraes V, Rabot S, Alcocer-Gonzalez JM, et al. A novel mucosal vaccine based on live Lactococci expressing E7 antigen and IL-12 induces systemic and mucosal immune responses and protects mice against human papillomavirus type 16-induced tumors. J Immunol. 2005;175(11):7297–302.PubMed
30.
Lin KY, Guarnieri FG, StaveleyOCarroll KF, Levitsky HI, August JT, Pardoll DM, et al. Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen. Cancer Res. 1996;56(1):21–6.PubMed
31.
Santiago C, Pagan B, Isidro AA, Appleyard CB. Prolonged chronic inflammation progresses to dysplasia in a novel rat model of colitis-associated colon cancer. Cancer Res. 2007;67(22):10766–73.PubMed
32.
Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248–54.CrossRef
33.
Mason KM, Bigley NJ, Fink PS. Development of a novel in vitro co-culture system for studying host response to native bacterial antigens. J Immunol Methods. 1998;211(1–2):147–58.PubMed
34.
Hazebrouck S, Przybylski-Nicaise L, Ah-Leung S, Adel-Patient K, Corthier G, Langella P, et al. Influence of the route of administration on immunomodulatory properties of bovine beta-lactoglobulin-producing Lactobacillus casei. Vaccine. 2009;27(42):5800–5.PubMed
35.
Yang M, Yang C, Mine Y. Multiple T cell epitope peptides suppress allergic responses in an egg allergy mouse model by the elicitation of forkhead box transcription factor 3- and transforming growth factor-beta-associated mechanisms. Clin Exp Allergy. 2010;40(4):668–78.PubMed
36.
Cha HR, Chang SY, Chang JH, Kim JO, Yang JY, Kim CH, et al. Downregulation of Th17 cells in the small intestine by disruption of gut flora in the absence of retinoic acid. J Immunol. 2010;184(12):6799–806.PubMed
37.
Cardoso CR, Provinciatto PR, Godoi DF, Ferreira BR, Teixeira G, Rossi MA, et al. IL-4 regulates susceptibility to intestinal inflammation in murine food allergy. Am J Physiol Gastrointest Liver Physiol. 2009;296(3):G593–600.PubMed
38.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods. 2001;25(4):402–8.
39.
De Simone V, Franze E, Ronchetti G, Colantoni A, Fantini MC, Di Fusco D, et al. Th17-type cytokines, IL-6 and TNF-alpha synergistically activate STAT3 and NF-kB to promote colorectal cancer cell growth. Oncog. 2015;34(27):3493–503.
40.
Murugaiyan G, Saha B. Protumor vs antitumor functions of IL-17. J Immunol. 2009;183(7):4169–75.PubMed
41.
Gounaris E, Blatner NR, Dennis K, Magnusson F, Gurish MF, Strom TB, et al. T-regulatory cells shift from a protective anti-inflammatory to a cancer-promoting proinflammatory phenotype in polyposis. Cancer Res. 2009;69(13):5490–7.PubMedPubMedCentral
42.
Tosolini M, Kirilovsky A, Mlecnik B, Fredriksen T, Mauger S, Bindea G, et al. Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer. Cancer Res. 2011;71(4):1263–71.PubMed
43.
Liu Y, Wang L, Predina J, Han R, Beier UH, Wang LC, et al. Inhibition of p300 impairs Foxp3(+) T regulatory cell function and promotes antitumor immunity. Nat Med. 2013;19(9):1173–7.PubMedPubMedCentral
44.
Lee YK, Mukasa R, Hatton RD, Weaver CT. Developmental plasticity of Th17 and Treg cells. Curr Opin Immunol. 2009;21(3):274–80.PubMed
45.
Ohnmacht C, Park JH, Cording S, Wing JB, Atarashi K, Obata Y, et al. The microbiota regulates type 2 immunity through RORγt+ T cells. Science. 2015;349(6251):989–93.PubMed
46.
Sawa S, Lochner M, Satoh-Takayama N, Dulauroy S, Berard M, Kleinschek M, et al. RORgammat+ innate lymphoid cells regulate intestinal homeostasis by integrating negative signals from the symbiotic microbiota. Nat Immunol. 2011;12(4):320–6.PubMed
Metadata
Title
RETRACTED ARTICLE: Lactobacillus casei BL23 regulates Treg and Th17 T-cell populations and reduces DMH-associated colorectal cancer
Authors
Marion Lenoir
Silvina del Carmen
Naima G. Cortes-Perez
Daniel Lozano-Ojalvo
Diego Muñoz-Provencio
Florian Chain
Philippe Langella
Alejandra de Moreno de LeBlanc
Jean Guy LeBlanc
Luis G. Bermúdez-Humarán
Publication date
01-09-2016
Publisher
Springer Japan
Published in
Journal of Gastroenterology / Issue 9/2016
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-015-1158-9

Other articles of this Issue 9/2016

Journal of Gastroenterology 9/2016 Go to the issue

Review

Stem cell dynamics and pretumor progression in the intestinal tract

Original Article—Liver, Pancreas, and Biliary Tract

Expression of connective tissue growth factor in the livers of non-viral hepatocellular carcinoma patients with metabolic risk factors

Review

Indole compounds may be promising medicines for ulcerative colitis

Original Article—Liver, Pancreas, and Biliary Tract

Obesity with abundant subcutaneous adipose tissue increases the risk of post-ERCP pancreatitis

Original Article—Liver, Pancreas, and Biliary Tract

Diagnostic performance and factors influencing the accuracy of EUS-FNA of pancreatic neuroendocrine neoplasms

Original Article—Alimentary Tract

Effect of ramosetron in female patients with irritable bowel syndrome with diarrhea: a phase III long-term study
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits