Top

Published in:

01-10-2020 | Respiratory Microbiota | PRECLINICAL STUDIES

Novel Bacillus strains from the human gut exert anticancer effects on a broad range of malignancy types

Authors: Man-Fei Zhao, Gong-Da Liang, Yu-Jie Zhou, Zhi-Ping Chi, He Zhuang, Song-Ling Zhu, Yao Wang, Gui-Rong Liu, Jing-Bo Zhao, Shu-Lin Liu

Published in: Investigational New Drugs | Issue 5/2020

Summary

Cancer is one of the leading causes of death worldwide, but effective therapies remain the topic of many research activities. Many recent studies have thus focused on particular gut microbiota due to their important roles in treating cancers, but very few microbes of therapeutic value have been reported. In this study, we isolated four bacterial strains, BY38, BY40, BY43 and BY45, from the fecal specimens of healthy individuals and cancer patients. The treatment of cancer cells with the products of these cultured bacteria induced significant inhibitory effects on the proliferation of ovarian cancer cells and colorectal cancer cells in a dose-dependent manner. A phylogenetic analysis showed that the four anticancer strains belong to the genus Bacillus, and flow cytometry assays indicated that the inhibitory effects might be achieved through the induction of cell apoptosis. These results suggest that these bacteria could be novel and promising anticancer agents against cancers.

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics, 2012. CA Cancer J Clin 65(2):87–108. https://doi.org/10.3322/caac.21262CrossRefPubMed

Siegel RL, Miller KD, Jemal A (2019) Cancer statistics, 2019. CA Cancer J Clin 69(1):7–34. https://doi.org/10.3322/caac.21551CrossRefPubMed

Danaei G, Vander Hoorn S, Lopez AD, Murray CJ, Ezzati M, Comparative Risk Assessment collaborating g (2005) Causes of cancer in the world: comparative risk assessment of nine behavioural and environmental risk factors. Lancet 366(9499):1784–1793. https://doi.org/10.1016/S0140-6736(05)67725-2CrossRef

Johnson CB, Davis MK, Law A, Sulpher J (2016) Shared risk factors for cardiovascular disease and Cancer: implications for preventive health and clinical Care in Oncology Patients. The Canadian journal of cardiology 32(7):900–907. https://doi.org/10.1016/j.cjca.2016.04.008CrossRefPubMed

Koene RJ, Prizment AE, Blaes A, Konety SH (2016) Shared risk factors in cardiovascular disease and Cancer. Circulation 133(11):1104–1114. https://doi.org/10.1161/CIRCULATIONAHA.115.020406CrossRefPubMedPubMedCentral

Albini A, Cavuto S, Apolone G, Noonan DM (2015) Strategies to prevent "bad luck" in Cancer. J Natl Cancer Inst 107(10). https://doi.org/10.1093/jnci/djv213

Yu T, Guo F, Yu Y, Sun T, Ma D, Han J, Qian Y, Kryczek I, Sun D, Nagarsheth N, Chen Y, Chen H, Hong J, Zou W, Fang JY (2017) Fusobacterium nucleatum promotes Chemoresistance to colorectal Cancer by modulating autophagy. Cell 170(3):548–563 e516. https://doi.org/10.1016/j.cell.2017.07.008CrossRefPubMedPubMedCentral

Mayor S (2015) Side-effects of cancer drugs are under-reported in trials. Lancet Oncol 16(3):e107. https://doi.org/10.1016/S1470-2045(15)70023-9CrossRefPubMed

Sun Y (2016) Tumor microenvironment and cancer therapy resistance. Cancer Lett 380(1):205–215. https://doi.org/10.1016/j.canlet.2015.07.044CrossRefPubMed

10.

Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, Benyamin FW, Lei YM, Jabri B, Alegre ML, Chang EB, Gajewski TF (2015) Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 350(6264):1084–1089. https://doi.org/10.1126/science.aac4255CrossRefPubMedPubMedCentral

11.

Zou W, Wolchok JD, Chen L (2016) PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: mechanisms, response biomarkers, and combinations. Sci Transl med 8 (328):328rv324. https://doi.org/10.1126/scitranslmed.aad7118

12.

Zitvogel L, Galluzzi L, Viaud S, Vetizou M, Daillere R, Merad M, Kroemer G (2015) Cancer and the gut microbiota: an unexpected link. Sci Transl Med 7(271):271ps271. https://doi.org/10.1126/scitranslmed.3010473CrossRef

13.

Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillere R, Fluckiger A, Messaoudene M, Rauber C, Roberti MP, Fidelle M, Flament C, Poirier-Colame V, Opolon P, Klein C, Iribarren K, Mondragon L, Jacquelot N, Qu B, Ferrere G, Clemenson C, Mezquita L, Masip JR, Naltet C, Brosseau S, Kaderbhai C, Richard C, Rizvi H, Levenez F, Galleron N, Quinquis B, Pons N, Ryffel B, Minard-Colin V, Gonin P, Soria JC, Deutsch E, Loriot Y, Ghiringhelli F, Zalcman G, Goldwasser F, Escudier B, Hellmann MD, Eggermont A, Raoult D, Albiges L, Kroemer G, Zitvogel L (2018) Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science New York, NY 359(6371):91–97. https://doi.org/10.1126/science.aan3706CrossRef

14.

Santoni M, Piva F, Conti A, Santoni A, Cimadamore A, Scarpelli M, Battelli N, Montironi R (2018) Re: gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Eur Urol 74(4):521–522. https://doi.org/10.1016/j.eururo.2018.05.033CrossRefPubMed

15.

Pardoll DM (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12(4):252–264. https://doi.org/10.1038/nrc3239CrossRefPubMedPubMedCentral

16.

Vetizou M, Pitt JM, Daillere R, Lepage P, Waldschmitt N, Flament C, Rusakiewicz S, Routy B, Roberti MP, Duong CP, Poirier-Colame V, Roux A, Becharef S, Formenti S, Golden E, Cording S, Eberl G, Schlitzer A, Ginhoux F, Mani S, Yamazaki T, Jacquelot N, Enot DP, Berard M, Nigou J, Opolon P, Eggermont A, Woerther PL, Chachaty E, Chaput N, Robert C, Mateus C, Kroemer G, Raoult D, Boneca IG, Carbonnel F, Chamaillard M, Zitvogel L (2015) Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350(6264):1079–1084. https://doi.org/10.1126/science.aad1329CrossRefPubMedPubMedCentral

17.

Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, Prieto PA, Vicente D, Hoffman K, Wei SC, Cogdill AP, Zhao L, Hudgens CW, Hutchinson DS, Manzo T, Petaccia de Macedo M, Cotechini T, Kumar T, Chen WS, Reddy SM, Szczepaniak Sloane R, Galloway-Pena J, Jiang H, Chen PL, Shpall EJ, Rezvani K, Alousi AM, Chemaly RF, Shelburne S, Vence LM, Okhuysen PC, Jensen VB, Swennes AG, McAllister F, Marcelo Riquelme Sanchez E, Zhang Y, Le Chatelier E, Zitvogel L, Pons N, Austin-Breneman JL, Haydu LE, Burton EM, Gardner JM, Sirmans E, Hu J, Lazar AJ, Tsujikawa T, Diab A, Tawbi H, Glitza IC, Hwu WJ, Patel SP, Woodman SE, Amaria RN, Davies MA, Gershenwald JE, Hwu P, Lee JE, Zhang J, Coussens LM, Cooper ZA, Futreal PA, Daniel CR, Ajami NJ, Petrosino JF, Tetzlaff MT, Sharma P, Allison JP, Jenq RR, Wargo JA (2018) Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science New York, NY 359(6371):97–103. https://doi.org/10.1126/science.aan4236CrossRef

18.

Zitvogel L, Daillere R, Roberti MP, Routy B, Kroemer G (2017) Anticancer effects of the microbiome and its products. Nat Rev Microbiol 15(8):465–478. https://doi.org/10.1038/nrmicro.2017.44CrossRefPubMed

19.

Viaud S, Saccheri F, Mignot G, Yamazaki T, Daillere R, Hannani D, Enot DP, Pfirschke C, Engblom C, Pittet MJ, Schlitzer A, Ginhoux F, Apetoh L, Chachaty E, Woerther PL, Eberl G, Berard M, Ecobichon C, Clermont D, Bizet C, Gaboriau-Routhiau V, Cerf-Bensussan N, Opolon P, Yessaad N, Vivier E, Ryffel B, Elson CO, Dore J, Kroemer G, Lepage P, Boneca IG, Ghiringhelli F, Zitvogel L (2013) The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science New York, NY 342(6161):971–976. https://doi.org/10.1126/science.1240537CrossRef

20.

Ho CL, Tan HQ, Chua KJ, Kang A, Lim KH, Ling KL, Yew WS, Lee YS, Thiery JP, Chang MW (2018) Engineered commensal microbes for diet-mediated colorectal-cancer chemoprevention. Nature biomedical engineering 2(1):27–37. https://doi.org/10.1038/s41551-017-0181-yCrossRefPubMed

21.

Barbe S, Van Mellaert L, Anne J (2006) The use of clostridial spores for cancer treatment. J Appl Microbiol 101(3):571–578. https://doi.org/10.1111/j.1365-2672.2006.02886.xCrossRefPubMed

22.

Van Mellaert L, Barbe S, Anne J (2006) Clostridium spores as anti-tumour agents. Trends Microbiol 14(4):190–196. https://doi.org/10.1016/j.tim.2006.02.002CrossRefPubMed

23.

Theys J, Pennington O, Dubois L, Anlezark G, Vaughan T, Mengesha A, Landuyt W, Anne J, Burke PJ, Durre P, Wouters BG, Minton NP, Lambin P (2006) Repeated cycles of Clostridium-directed enzyme prodrug therapy result in sustained antitumour effects in vivo. Br J Cancer 95(9):1212–1219. https://doi.org/10.1038/sj.bjc.6603367CrossRefPubMedPubMedCentral

24.

Thiele EH, Arison RN, Boxer GE (1964) Oncolysis by clostridia. Iv. Effect of nonpathogenic Clostridial spores in Normal and pathological tissues. Cancer Res 24:234–238PubMed

25.

Zhou S, Gravekamp C, Bermudes D, Liu K (2018) Tumour-targeting bacteria engineered to fight cancer. Nat Rev Cancer 18(12):727–743. https://doi.org/10.1038/s41568-018-0070-zCrossRefPubMedPubMedCentral

26.

Krick EL, Sorenmo KU, Rankin SC, Cheong I, Kobrin B, Thornton K, Kinzler KW, Vogelstein B, Zhou S, Diaz LA Jr (2012) Evaluation of Clostridium novyi-NT spores in dogs with naturally occurring tumors. Am J Vet Res 73(1):112–118. https://doi.org/10.2460/ajvr.73.1.112CrossRefPubMedPubMedCentral

27.

Michl P, Buchholz M, Rolke M, Kunsch S, Lohr M, McClane B, Tsukita S, Leder G, Adler G, Gress TM (2001) Claudin-4: a new target for pancreatic cancer treatment using Clostridium perfringens enterotoxin. Gastroenterology 121(3):678–684. https://doi.org/10.1053/gast.2001.27124CrossRefPubMed

28.

Bhave MS, Hassanbhai AM, Anand P, Luo KQ, Teoh SH (2015) Effect of heat-inactivated Clostridium sporogenes and its conditioned media on 3-dimensional colorectal Cancer cell models. Sci Rep 5:15681. https://doi.org/10.1038/srep15681CrossRefPubMedPubMedCentral

29.

Zhou YJ, Zhao DD, Liu H, Chen HT, Li JJ, Mu XQ, Liu Z, Li X, Tang L, Zhao ZY, Wu JH, Cai YX, Huang YZ, Wang PG, Jia YY, Liang PQ, Peng X, Chen SY, Yue ZL, Yuan XY, Lu T, Yao BQ, Li YG, Liu GR, Liu SL (2017) Cancer killers in the human gut microbiota: diverse phylogeny and broad spectra. Oncotarget 8(30):49574–49591. https://doi.org/10.18632/oncotarget.17319CrossRefPubMedPubMedCentral

30.

Breitbach CJ, Burke J, Jonker D, Stephenson J, Haas AR, Chow LQ, Nieva J, Hwang TH, Moon A, Patt R, Pelusio A, Le Boeuf F, Burns J, Evgin L, De Silva N, Cvancic S, Robertson T, Je JE, Lee YS, Parato K, Diallo JS, Fenster A, Daneshmand M, Bell JC, Kirn DH (2011) Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans. Nature 477(7362):99–102. https://doi.org/10.1038/nature10358CrossRefPubMed

31.

Jacouton E, Chain F, Sokol H, Langella P, Bermudez-Humaran LG (2017) Probiotic strain Lactobacillus casei BL23 prevents colitis-associated colorectal Cancer. Front Immunol 8:1553. https://doi.org/10.3389/fimmu.2017.01553CrossRefPubMedPubMedCentral

32.

Roberts NJ, Zhang L, Janku F, Collins A, Bai RY, Staedtke V, Rusk AW, Tung D, Miller M, Roix J, Khanna KV, Murthy R, Benjamin RS, Helgason T, Szvalb AD, Bird JE, Roy-Chowdhuri S, Zhang HH, Qiao Y, Karim B, McDaniel J, Elpiner A, Sahora A, Lachowicz J, Phillips B, Turner A, Klein MK, Post G, Diaz LA Jr, Riggins GJ, Papadopoulos N, Kinzler KW, Vogelstein B, Bettegowda C, Huso DL, Varterasian M, Saha S, Zhou S (2014) Intratumoral injection of Clostridium novyi-NT spores induces antitumor responses. Science Translational Medicine 6(249):249ra111. https://doi.org/10.1126/scitranslmed.3008982CrossRefPubMedPubMedCentral

33.

Jeong MH, Lee YS, Cho JY, Ahn YS, Moon JH, Hyun HN, Cha GS, Kim KY (2017) Isolation and characterization of metabolites from Bacillus licheniformis MH48 with antifungal activity against plant pathogens. Microb Pathog 110:645–653. https://doi.org/10.1016/j.micpath.2017.07.027CrossRefPubMed

34.

Wang Y, Du W, Lei K, Wang B, Wang Y, Zhou Y, Li W (2017) Effects of dietary Bacillus licheniformis on gut physical barrier, immunity, and reproductive hormones of laying hens. Probiotics Antimicrob Proteins 9(3):292–299. https://doi.org/10.1007/s12602-017-9252-3CrossRefPubMed

35.

Kim Y, Cho JY, Kuk JH, Moon JH, Cho JI, Kim YC, Park KH (2004) Identification and antimicrobial activity of phenylacetic acid produced by Bacillus licheniformis isolated from fermented soybean, Chungkook-Jang. Curr Microbiol 48(4):312–317. https://doi.org/10.1007/s00284-003-4193-3CrossRefPubMed

Title: Novel Bacillus strains from the human gut exert anticancer effects on a broad range of malignancy types
Authors: Man-Fei Zhao
Gong-Da Liang
Yu-Jie Zhou
Zhi-Ping Chi
He Zhuang
Song-Ling Zhu
Yao Wang
Gui-Rong Liu
Jing-Bo Zhao
Shu-Lin Liu
Publication date: 01-10-2020
Publisher: Springer US
Keyword: Respiratory Microbiota
Published in: Investigational New Drugs / Issue 5/2020
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-020-00906-5

2024 ASCO Annual Meeting Coverage

Highlights of the Day: Breast cancer – metastatic

Breast Cancer Video

In this session, Dr. Wolff provides his key takeaways from the data presented in the metastatic breast cancer oral abstract session at ASCO 2024.

Watch now

Highlights of the Day: Gynecologic cancer

Gynecologic Cancer Video

Highlights of the Day: Breast Cancer – local/regional/adjuvant

Breast Cancer Video

Neoadjuvant dual immunotherapy improves melanoma outcomes

04-06-2024 Melanoma News

» View more highlights on the ASCO 2024 congress hub page

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Image Credits

ASCO 2024 | Highlights of the Day: Breast cancer – metastatic/© 2024 American Society of Clinical Oncology, all rights reserved., ASCO 2024 | Highlights of the Day: Gynecologic Cancer/© 2024 American Society of Clinical Oncology, all rights reserved., ASCO 2024 | Highlights of the Day: Breast Cancer – local/regional/adjuvant/© 2024 American Society of Clinical Oncology, all rights reserved., Melanoma/© selvanegra / Getty Images / iStock, Antibody drug conjugated with cytotoxic payload/© Love Employee / Getty images / iStock

2024 ASCO Annual Meeting

Springer Medicine

Summary

Please log in to get access to this content

Other articles of this Issue 5/2020

Sorafenib may enhance antitumour efficacy in hepatocellular carcinoma patients by modulating the proportions and functions of natural killer cells

Phase I dose escalation study of BI 836826 (CD37 antibody) in patients with relapsed or refractory B-cell non-Hodgkin lymphoma

Structure-based design, synthesis, and evaluation of the biological activity of novel phosphoroorganic small molecule IAP antagonists

Phase 1 study of the protein deubiquitinase inhibitor VLX1570 in patients with relapsed and/or refractory multiple myeloma

Microarray expression profiles and bioinformatics analysis of mRNAs, lncRNAs, and circRNAs in the secondary temozolomide-resistant glioblastoma