We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine

Probiotics Clostridium butyricum and Bacillus subtilis ameliorate intestinal tumorigenesis

    Zhao-Fei Chen

    Division of Gastroenterology & Hepatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University; Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China

    These authors contributed equally

    Search for more papers by this author

    ,
    Luo-Yan Ai

    Division of Gastroenterology & Hepatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University; Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China

    These authors contributed equally

    Search for more papers by this author

    ,
    Ji-Lin Wang

    Division of Gastroenterology & Hepatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University; Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China

    ,
    Lin-Lin Ren

    Division of Gastroenterology & Hepatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University; Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China

    ,
    Ya-Nan Yu

    Division of Gastroenterology & Hepatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University; Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China

    ,
    Jie Xu

    Division of Gastroenterology & Hepatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University; Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China

    ,
    Hao-Yan Chen

    Division of Gastroenterology & Hepatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University; Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China

    ,
    Jun Yu

    Department of Medicine & Therapeutics, Institute of Digestive Disease & LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong

    ,
    Min Li

    Department of Clinical Laboratory, Renji Hospital, School of Medicine, Shanghai Jiaotong University, China

    ,
    Wen-Xin Qin

    State Key Laboratory of Oncogenes & Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiaotong University Shanghai, China

    ,
    Xiong Ma

    Division of Gastroenterology & Hepatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University; Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China

    ,
    Nan Shen

    Division of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, China

    ,
    Ying-Xuan Chen

    ***Author for correspondence:

    E-mail Address: yingxuanchen71@126.com

    Division of Gastroenterology & Hepatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University; Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China

    ,
    Jie Hong

    **Author for correspondence:

    E-mail Address: jiehong97@gmail.com

    Division of Gastroenterology & Hepatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University; Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China

    &
    Jing-Yuan Fang

    *Author for correspondence:

    E-mail Address: jingyuanfang_new@163.com

    Division of Gastroenterology & Hepatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University; Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China

    Published Online:https://doi.org/10.2217/fmb.15.66

    Aims: To investigate the antitumor effects of probiotics Clostridium butyricum and Bacillus subtilis on colorectal cancer (CRC) progression. Materials & methods: The effects of C. butyricum and B. subtilis on CRC cells were studied. Male C57BL/6 mice with 1,2-dimethylhydrazine dihydrochloride (DMH)-induced CRC were intervened by these two probiotics and the antitumor effects were examined by comparing the tumor incidence and detecting the inflammatory and immune-related markers. Results & conclusions: C. butyricum and B. subtilis inhibited the proliferation of CRC cells, caused cell cycle arrest and promoted apoptosis. In vivo, these two probiotics inhibited the development of DMH-induced CRC. The molecular mechanism involved reduced inflammation and improved immune homeostasis. This work establishes a basis for the protective role of probiotics B. subtilis and C. butyricum in intestinal tumorigenesis.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

    References

    • 1 Wang T, Cai G, Qiu Y et al. Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. ISME J. 6(2), 320–329 (2012).•• A good article showed that difference of gut microbiota did exist between colorectal cancer patients and healthy people.
    • 2 Zhang L, Cao GT, Zeng XF et al. Effects of clostridium butyricum on growth performance, immune function, and cecal microflora in broiler chickens challenged with Escherichia coli k88. Poultry Sci. 93(1), 46–53 (2014).
    • 3 Zhang HQ, Ding TT, Zhao JS et al. Therapeutic effects of Clostridium butyricum on experimental colitis induced by oxazolone in rats. World J. Gastroenterol. 15(15), 1821–1828 (2009).
    • 4 Kong Q, He GQ, Jia JL, Zhu QL, Ruan H. Oral administration of Clostridium butyricum for modulating gastrointestinal microflora in mice. Curr. Microbiol. 62(2), 512–517 (2011).
    • 5 Takahashi M, Taguchi H, Yamaguchi H, Osaki T, Komatsu A, Kamiya S. The effect of probiotic treatment with Clostridium butyricum on enterohemorrhagic Escherichia coli o157: H7 infection in mice. FEMS Immunol. Med. Microbiol. 41(3), 219–226 (2004).
    • 6 Chen HM, Yu YN, Wang JL et al. Decreased dietary fiber intake and structural alteration of gut microbiota in patients with advanced colorectal adenoma. Am. J. Clin. Nutr. 97(5), 1044–1052 (2013).•• Our previous work suggested that gut microbiota structure was altered in patients with advanced colorectal adenoma.
    • 7 Volker U, Hecker M. From genomics via proteomics to cellular physiology of the Gram-positive model organism Bacillus subtilis. Cell. Microbiol. 7(8), 1077–1085 (2005).
    • 8 Fujiya M, Musch MW, Nakagawa Y et al. The Bacillus subtilis quorum-sensing molecule CSF contributes to intestinal homeostasis via OCTN2, a host cell membrane transporter. Cell Host Microbe 1(4), 299–308 (2007).
    • 9 Chen S, Fu Y, Liu LL et al. Live combined Bacillus subtilis and Enterococcus faecium ameliorate murine experimental colitis by immunosuppression. Int. J. Inflamm. 2014, 878054 (2014).• This article demonstrated that Bacillus subtilis could ameliorate murine experimental colitis, hinting this probiotics may have a role in colorectal cancer.
    • 10 Rescigno M. Intestinal microbiota and its effects on the immune system. Cell. Microbiol. 16(7), 1004–1013 (2014).
    • 11 Cho JH. The genetics and immunopathogenesis of inflammatory bowel disease. Nat. Rev. Immunol. 8(6), 458–466 (2008).
    • 12 Li Y, Deuring J, Peppelenbosch MP, Kuipers EJ, De Haar C, Van Der Woude CJ. IL-6-induced DNMT1 activity mediates SOCS3 promoter hypermethylation in ulcerative colitis-related colorectal cancer. Carcinogenesis 33(10), 1889–1896 (2012).
    • 13 Rakoff-Nahoum S, Medzhitov R. Regulation of spontaneous intestinal tumorigenesis through the adaptor protein MyD88. Science 317(5834), 124–127 (2007).
    • 14 Su LK, Kinzler KW, Vogelstein B et al. Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene. Science 256(5057), 668–670 (1992).
    • 15 Kostic AD, Chun E, Robertson L et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe 14(2), 207–215 (2013).
    • 16 Rosenberg DW, Giardina C, Tanaka T. Mouse models for the study of colon carcinogenesis. Carcinogenesis 30(2), 183–196 (2009).
    • 17 Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. Cancer J. Clin. 64(1), 9–29 (2014).
    • 18 Yam C, Zhao M, Hayashi K et al. Monotherapy with a tumor-targeting mutant of S. typhimurium inhibits liver metastasis in a mouse model of pancreatic cancer. J. Surg. Res. 164(2), 248–255 (2010).
    • 19 Hiroshima Y, Zhang Y, Murakami T et al. Efficacy of tumor-targeting Salmonella typhimurium A1-R in combination with anti-angiogenesis therapy on a pancreatic cancer patient-derived orthotopic xenograft (PDOX) and cell line mouse models. Oncotarget 5(23), 12346–12357 (2014).
    • 20 Hiroshima Y, Zhao M, Maawy A et al. Efficacy of Salmonella typhimurium A1-R versus chemotherapy on a pancreatic cancer patient-derived orthotopic xenograft (PDOX). J. Cell. Biochem. 115(7), 1254–1261 (2014).
    • 21 Momiyama M, Zhao M, Kimura H et al. Inhibition and eradication of human glioma with tumor-targeting Salmonella typhimurium in an orthotopic nude-mouse model. Cell Cycle 11(3), 628–632 (2012).
    • 22 Kimura H, Zhang L, Zhao M et al. Targeted therapy of spinal cord glioma with a genetically modified Salmonella typhimurium. Cell Prolif. 43(1), 41–48 (2010).
    • 23 Miwa S, Zhang Y, Baek KE et al. Inhibition of spontaneous and experimental lung metastasis of soft-tissue sarcoma by tumor-targeting Salmonella typhimurium A1-R. Oncotarget 5(24), 12849–12861 (2014).
    • 24 Hayashi K, Zhao M, Yamauchi K et al. Systemic targeting of primary bone tumor and lung metastasis of high-grade osteosarcoma in nude mice with a tumor-selective strain of Salmonella typhimurium. Cell Cycle 8(6), 870–875 (2009).
    • 25 Matsumoto Y, Miwa S, Zhang Y et al. Efficacy of tumor-targeting Salmonella typhimurium A1-R on nude mouse models of metastatic and disseminated human ovarian cancer. J. Cell. Biochemi. 115(11), 1996–2003 (2014).
    • 26 Guarner F, Malagelada JR. Gut flora in health and disease. Lancet 361(9356), 512–519 (2003).
    • 27 Rafter J. The effects of probiotics on colon cancer development. Nutr. Res. Rev. 17(2), 277–284 (2004).
    • 28 Uccello M, Malaguarnera G, Basile F et al. Potential role of probiotics on colorectal cancer prevention. BMC Surg. 12(Suppl. 1), S35 (2012).•• We can get some basic knowledge in the field we studied.
    • 29 Mohania D, Kansal VK, Kruzliak P, Kumari A. Probiotic Dahi containing Lactobacillus acidophilus and Bifidobacterium bifidum modulates the formation of aberrant crypt foci, mucin depleted foci and cell proliferation on 1, 2-dimethylhydrazine induced colorectal carcinogenesis in wistar rats. Rejuv. Res. 325–333 (2014).
    • 30 Verma A, Shukla G. Probiotics Lactobacillus rhamnosus GG, Lactobacillus acidophilus suppresses DMH-induced procarcinogenic fecal enzymes and preneoplastic aberrant crypt foci in early colon carcinogenesis in Sprague Dawley rats. Nutr. Cancer 65(1), 84–91 (2013).
    • 31 Arimochi H, Kinouchi T, Kataoka K, Kuwahara T, Ohnishi Y. Effect of intestinal bacteria on formation of azoxymethane-induced aberrant crypt foci in the rat colon. Biochem. Biophys. Res. Commun. 238(3), 753–757 (1997).
    • 32 Ohkawara S, Furuya H, Nagashima K, Asanuma N, Hino T. Oral administration of Butyrivibrio fibrisolvens, a butyrate-producing bacterium, decreases the formation of aberrant crypt foci in the colon and rectum of mice. J. Nutr. 135(12), 2878–2883 (2005).
    • 33 Chen HM, Lin YW, Wang JL, Kong X, Hong J, Fang JY. Identification of potential target genes of butyrate in dimethylhydrazine-induced colorectal cancer in mice. Nutr. Cancer 65(8), 1171–1183 (2013).• Our previous work showed that butyrate could be beneficial in colorectal cancer.
    • 34 Isono A, Katsuno T, Sato T et al. Clostridium butyricum TO-A culture supernatant downregulates TLR4 in human colonic epithelial cells. Dig. Dis. Sci. 52(11), 2963–2971 (2007).
    • 35 Ohnmacht C, Marques R, Presley L, Sawa S, Lochner M, Eberl G. Intestinal microbiota, evolution of the immune system and the bad reputation of pro-inflammatory immunity. Cell. Microbiol. 13(5), 653–659 (2011).
    • 36 He D, Li H, Yusuf N et al. IL-17 mediated inflammation promotes tumor growth and progression in the skin. PLoS ONE 7(2), e32126 (2012).
    • 37 Wang L, Yi T, Zhang W, Pardoll DM, Yu H. IL-17 enhances tumor development in carcinogen-induced skin cancer. Cancer Res. 70(24), 10112–10120 (2010).
    • 38 Wu SG, Rhee KJ, Albesiano E et al. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat. Med. 15(9), 1016–1022 (2009).
    • 39 Gartel AL, Radhakrishnan SK. Lost in transcription: p21 repression, mechanisms, and consequences. Cancer Res. 65(10), 3980–3985 (2005).
    • 40 Xiong H, Zhang ZG, Tian XQ et al. Inhibition of JAK1, 2/STAT3 signaling induces apoptosis, cell cycle arrest, and reduces tumor cell invasion in colorectal cancer cells. Neoplasia 10(3), 287–297 (2008).