Probiotic Bacteria: A Promising Tool in Cancer Prevention and Therapy

Current Microbiology - Tập 76 - Trang 939-949 - 2019
Agata Górska1, Dawid Przystupski2, Magdalena J. Niemczura1, Julita Kulbacka3
1Department of Biological Sciences, Institute of Experimental Biology, University of Wrocław, Wrocław, Poland
2Faculty of Medicine, Wroclaw Medical University, Wrocław, Poland
3Department of Molecular and Cellular Biology, Wroclaw Medical University, Wrocław, Poland

Tóm tắt

Gut microbiota is widely considered to be one of the most important components to maintain balanced homeostasis. Looking forward, probiotic bacteria have been shown to play a significant role in immunomodulation and display antitumour properties. Bacterial strains could be responsible for detection and degradation of potential carcinogens and production of short-chain fatty acids, which affect cell death and proliferation and are known as signaling molecules in the immune system. Lactic acid bacteria present in the gut has been shown to have a role in regression of carcinogenesis due to their influence on immunomodulation, which can stand as a proof of interaction between bacterial metabolites and immune and epithelial cells. Probiotic bacteria have the ability to both increase and decrease the production of anti-inflammatory cytokines which play an important role in prevention of carcinogenesis. They are also capable of activating phagocytes in order to eliminate early-stage cancer cells. Application of heat-killed probiotic bacteria coupled with radiation had a positive influence on enhancing immunological recognition of cancer cells. In the absence of active microbiota, murine immunity to carcinogens has been decreased. There are numerous cohort studies showing the correlation between ingestion of dairy products and the risk of colon and colorectal cancer. An idea of using probiotic bacteria as vectors to administer drugs has emerged lately as several papers presenting successful results have been revealed. Within the next few years, probiotic bacteria as well as gut microbiota are likely to become an important component in cancer prevention and treatment.

Tài liệu tham khảo

Goldin BR, Gorbach SL (1980) Effect of Lactobacillus acidophilus dietary supplements on 1,2-dimethylhydrazine dihydrochloride-induced intestinal cancer in rats. J Natl Cancer Inst 64:263–265 Kim Y, Lee D, Kim D et al (2008) Inhibition of proliferation in colon cancer cell lines and harmful enzyme activity of colon bacteria by Bifidobacterium adolescentis SPM0212. Arch Pharm Res 31:468–473. https://doi.org/10.1007/s12272-001-1180-y Thirabunyanon M, Boonprasom P, Niamsup P (2009) Probiotic potential of lactic acid bacteria isolated from fermented dairy milks on antiproliferation of colon cancer cells. Biotechnol Lett 31:571–576. https://doi.org/10.1007/s10529-008-9902-3 Altonsy MO, Andrews SC, Tuohy KM (2010) Differential induction of apoptosis in human colonic carcinoma cells (Caco-2) by Atopobium, and commensal, probiotic and enteropathogenic bacteria: mediation by the mitochondrial pathway. Int J Food Microbiol 137:190–203. https://doi.org/10.1016/j.ijfoodmicro.2009.11.015 Ma EL, Choi YJ, Choi J et al (2010) The anticancer effect of probiotic Bacillus polyfermenticus on human colon cancer cells is mediated through ErbB2 and ErbB3 inhibition. Int J Cancer 127:780–790. https://doi.org/10.1002/ijc.25011 Orlando A, Refolo MG, Messa C et al (2012) Antiproliferative and proapoptotic effects of viable or heat-killed Lactobacillus paracasei IMPC2.1 and Lactobacillus rhamnosus GG in HGC-27 gastric and DLD-1 colon cell lines. Nutr Cancer 64:1103–1111. https://doi.org/10.1080/01635581.2012.717676 Thirabunyanon M, Hongwittayakorn P (2013) Potential probiotic lactic acid bacteria of human origin induce antiproliferation of colon cancer cells via synergic actions in adhesion to cancer cells and short-chain fatty acid bioproduction. Appl Biochem Biotechnol 169:511–525. https://doi.org/10.1007/s12010-012-9995-y Sadeghi-Aliabadi H, Mohammadi F, Fazeli H, Mirlohi M (2014) Effects of Lactobacillus plantarum A7 with probiotic potential on colon cancer and normal cells proliferation in comparison with a commercial strain. Iran J Basic Med Sci 17:815–819 Chen Z-F, Ai L-Y, Wang J-L et al (2015) Probiotics Clostridium butyricum and Bacillus subtilis ameliorate intestinal tumorigenesis. Future Microbiol 10:1433–1445. https://doi.org/10.2217/fmb.15.66 Lee NK, Son SH, Jeon EB et al (2015) The prophylactic effect of probiotic Bacillus polyfermenticus KU3 against cancer cells. J Funct Foods 14:513–518. https://doi.org/10.1016/j.jff.2015.02.019 Han KJ, Lee NK, Park H, Paik HD (2015) Anticancer and anti-inflammatory activity of probiotic Lactococcus lactis nk34. J Microbiol Biotechnol 25:1697–1701. https://doi.org/10.4014/jmb.1503.03033 Tiptiri-Kourpeti A, Spyridopoulou K, Santarmaki V et al (2016) Lactobacillus casei exerts anti-proliferative effects accompanied by apoptotic cell death and up-regulation of TRAIL in colon carcinoma cells. PLoS ONE. https://doi.org/10.1371/journal.pone.0147960 Saxami G, Karapetsas A, Lamprianidou E et al (2016) Two potential probiotic lactobacillus strains isolated from olive microbiota exhibit adhesion and anti-proliferative effects in cancer cell lines. J Funct Foods 24:461–471. https://doi.org/10.1016/j.jff.2016.04.036 Arvind Singh NK, Sinha PR (2009) Inhibition of 1,2 dimethylhydrazine induced genotoxicity in rats by the administration of probiotic curd. Int J Probiotics Prebiotics 4:201–203. https://doi.org/10.1007/s11033-009-9519-1 Kim SW, Kim HM, Yang KM et al (2010) Bifidobacterium lactis inhibits NF-κB in intestinal epithelial cells and prevents acute colitis and colitis-associated colon cancer in mice. Inflamm Bowel Dis 16:1514–1525. https://doi.org/10.1002/ibd.21262 Appleyard CB, Cruz ML, Isidro AA et al (2011) Pretreatment with the probiotic VSL#3 delays transition from inflammation to dysplasia in a rat model of colitis-associated cancer. Am J Physiol Liver Physiol 301:G1004–G1013. https://doi.org/10.1152/ajpgi.00167.2011 Verma A, Shukla G (2014) Synbiotic (Lactobacillus rhamnosus + Lactobacillus acidophilus + inulin) attenuates oxidative stress and colonic damage in 1,2 dimethylhydrazine dihydrochloride-induced colon carcinogenesis in Sprague’ Dawley rats: a long-term study. Eur J Cancer Prev 23:550–559. https://doi.org/10.1097/CEJ.0000000000000054 Lee HA, Kim H, Lee K-W, Park K-Y (2015) Dead nano-sized Lactobacillus plantarum inhibits azoxymethane/dextran sulfate sodium-induced colon cancer in Balb/c mice. J Med Food 18:1400–1405. https://doi.org/10.1089/jmf.2015.3577 Hu J, Wang C, Ye L et al (2015) Anti-tumour immune effect of oral administration of Lactobacillus plantarum to CT26 tumour-bearing mice. J Biosci 40:269–279. https://doi.org/10.1007/s12038-015-9518-4 Talero E, Bolivar S, Ávila-Román J et al (2015) Inhibition of chronic ulcerative colitis-associated adenocarcinoma development in mice by VSL#3. Inflamm Bowel Dis 21:1027–1037. https://doi.org/10.1097/MIB.0000000000000346 Walia S, Kamal R, Kanwar SS, Dhawan DK (2015) Cyclooxygenase as a target in chemoprevention by probiotics during 1,2-dimethylhydrazine induced colon carcinogenesis in rats. Nutr Cancer 67:603–611. https://doi.org/10.1080/01635581.2015.1011788 Zhang M, Fan X, Fang B et al (2015) Effects of Lactobacillus salivarius Ren on cancer prevention and intestinal microbiota in 1, 2-dimethylhydrazine-induced rat model. J Microbiol 53:398–405. https://doi.org/10.1007/s12275-015-5046-z Kuugbee ED, Shang X, Gamallat Y et al (2016) Structural change in microbiota by a probiotic cocktail enhances the gut barrier and reduces cancer via TLR2 signaling in a rat model of colon cancer. Dig Dis Sci 61:2908–2920. https://doi.org/10.1007/s10620-016-4238-7 Gamallat Y, Meyiah A, Kuugbee ED et al (2016) Lactobacillus rhamnosus induced epithelial cell apoptosis, ameliorates inflammation and prevents colon cancer development in an animal model. Biomed Pharmacother 83:536–541. https://doi.org/10.1016/j.biopha.2016.07.001 Dubey V, Ghosh AR, Bishayee K, Khuda-Bukhsh AR (2016) Appraisal of the anti-cancer potential of probiotic Pediococcus pentosaceus GS4 against colon cancer: in vitro and in vivo approaches. J Funct Foods 23:66–79. https://doi.org/10.1016/j.jff.2016.02.032 Lenoir M, del Carmen S, Cortes-Perez NG et al (2016) Lactobacillus casei BL23 regulates Tregand Th17 T-cell populations and reduces DMH-associated colorectal cancer. J Gastroenterol 51:862–873. https://doi.org/10.1007/s00535-015-1158-9 Jia W, Xie G, Jia W (2017) Bile acid–microbiota crosstalk in gastrointestinal inflammation and carcinogenesis. Nat Rev Gastroenterol Hepatol. https://doi.org/10.1038/nrgastro.2017.119 Bernstein H, Bernstein C, Payne CM et al (2005) Bile acids as carcinogens in human gastrointestinal cancers. Mutat Res 589:47–65 Biasco G, Paganelli GM, Brandi G et al (1991) Effect of Lactobacillus acidophilus and Bifidobacterium bifidum on rectal cell kinetics and fecal pH. Ital J Gastroenterol 23:142 Lidbeck A, Allinger UG, Orrhage KM et al (1991) Impact of Lactobacillus acidophilus supplements on the faecal microflora and soluble faecal bile acids in colon cancer patients. Microb Ecol Health Dis 4:81–88. https://doi.org/10.3109/08910609109140267 Goldin B, Gorbach SL (1977) Alterations in fecal microflora enzymes related to diet, age, lactobacillus supplements, and dimethylhydrazine. Cancer 40:2421–2426. https://doi.org/10.1002/1097-0142(197711)40:5+%3c2421:AID-CNCR2820400905%3e3.0.CO;2-I Kim DHDH, Jin YHYH (2001) Intestinal bacterial beta-glucuronidase activity of patients with colon cancer. Arch Pharm Res 24:564–567. https://doi.org/10.1007/BF02975166 Goldin BR, Swenson L, Dwyer J et al (1980) Effect of diet and Lactobacillus acidophilus supplements on human fecal bacterial enzymes. J Natl Cancer Inst 64:255–261 Gorbach SL (1976) The relationship between diet and rat fecal bacterial enzymes implicated in colon cancer. J Natl Cancer Inst 57:371–375. https://doi.org/10.1093/jnci/57.2.371 Goldin BR, Gorbach SL (1984) Alterations of the intestinal microflora by diet, oral antibiotics, and lactobacillus: decreased production of free amines from aromatic nitro compounds, azo dyes, and glucuronides. J Natl Cancer Inst 73:689–695. https://doi.org/10.1093/jnci/73.3.689 Kulkarni N, Reddy BS (1994) Inhibitory effect of Bifidobacterium iongum cultures on the azoxymethane-induced aberrant crypt foci formation and fecal bacterial -glucuronidase. Exp Biol Med 207:278–283. https://doi.org/10.3181/00379727-207-43817 Rowland IR, Rumney CJ, Coutts JT, Lievense LC (1998) Effect of Bifidobacterium longum and inulin on gut bacterial metabolism and carcinogen-induced aberrant crypt foci in rats. Carcinogenesis 19:281–285. https://doi.org/10.1093/carcin/19.2.281 Singh J, Rivenson A, Tomita M et al (1997) Bifidobacterium longum, a lactic acid-producing intestinal bacterium inhibits colon cancer and modulates the intermediate biomarkers of colon carcinogenesis. Carcinogenesis 18:833–841. https://doi.org/10.1093/carcin/18.4.833 Hirayama K, Rafter J (2000) The role of probiotic bacteria in cancer prevention. Microbes Infect 2:681–686. https://doi.org/10.1016/S1286-4579(00)00357-9 Lidbeck A, Övervik E, Rafter J et al (1992) Effect of Lactobacillus acidophilus supplements on mutagen excretion in faeces and urine in humans. Microb Ecol Health Dis 5:59–67. https://doi.org/10.3109/08910609209141305 Hayatsu H, Hayatsu T (1993) Suppressing effect of Lactobacillus casei administration on the urinary mutagenicity arising from ingestion of fried ground beef in the human. Cancer Lett 73:173–179 Orrhage KM, Annas A, Nord CE et al (2002) Effects of lactic acid bacteria on the uptake and distribution of the food mutagen Trp-P-2 in mice. Scand J Gastroenterol 37:215–221 Nowak A, Kuberski S, Libudzisz Z (2014) Probiotic lactic acid bacteria detoxify N-nitrosodimethylamine. Food Addit Contam Part A 31:1678–1687. https://doi.org/10.1080/19440049.2014.943304 Faridnia F, Hussin ASM, Saari N et al (2010) In vitro binding of mutagenic heterocyclic aromatic amines by Bifidobacterium pseudocatenulatum G4. Benef Microbes 1:149–154. https://doi.org/10.3920/BM2009.0035 Stidl R, Sontag G, Koller V, Knasmüller S (2008) Binding of heterocyclic aromatic amines by lactic acid bacteria: results of a comprehensive screening trial. Mol Nutr Food Res 52:322–329. https://doi.org/10.1002/mnfr.200700034 Orrhage K, Sillerström E, Gustafsson JÅ et al (1994) Binding of mutagenic heterocyclic amines by intestinal and lactic acid bacteria. Mutat Res Regul Pap 311:239–248. https://doi.org/10.1016/0027-5107(94)90182-1 Nowak A, Libudzisz Z (2009) Ability of probiotic Lactobacillus casei DN 114001 to bind or/and metabolise heterocyclic aromatic amines in vitro. Eur J Nutr 48:419–427. https://doi.org/10.1007/s00394-009-0030-1 Peltonen KD, El-Nezami HS, Salminen SJ, Ahokas JT (2000) Binding of aflatoxin B1 by probiotic bacteria. J Sci Food Agric 80:1942–1945. https://doi.org/10.1002/1097-0010(200010)80:13%3c1942:AID-JSFA741%3e3.0.CO;2-7 Duangjitcharoen Y, Kantachote D, Prasitpuripreecha C et al (2014) Selection and characterization of probiotic lactic acid bacteria with heterocyclic amine binding and nitrosamine degradation properties. J Appl Pharm Sci 4:14–23. https://doi.org/10.7324/JAPS.2014.40703 Nowak A, Czyżowska A, Stańczyk M (2015) Protective activity of probiotic bacteria against 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenyl-1H-imidazo[4,5-b]pyridine (PhIP) – an in vitro study. Food Addit Contam 32:1927–1938. https://doi.org/10.1080/19440049.2015.1084651 Nowak A, Ślizewska K, Błasiak J, Libudzisz Z (2014) The influence of Lactobacillus casei DN 114 001 on the activity of faecal enzymes and genotoxicity of faecal water in the presence of heterocyclic aromatic amines. Anaerobe 30:129–136. https://doi.org/10.1016/j.anaerobe.2014.09.014 Lili Z, Junyan W, Hongfei Z et al (2017) Detoxification of cancerogenic compounds by lactic acid bacteria strains. Crit Rev Food Sci Nutr 0:1–16. https://doi.org/10.1080/10408398.2017.1339665 Commane D, Hughes R, Shortt C, Rowland I (2005) The potential mechanisms involved in the anti-carcinogenic action of probiotics. Mutat Res 591:276–289 Garret WS (2015) Cancer and the microbiota. Science 348:80–86. https://doi.org/10.1126/science.aaa6204 Requena T, Martinez-Cuesta MC, Peláez C (2018) Diet and microbiota linked in health and disease. Food Funct. https://doi.org/10.1039/C7FO01820G LeBlanc JG, Chain F, Martín R et al (2017) Beneficial effects on host energy metabolism of short-chain fatty acids and vitamins produced by commensal and probiotic bacteria. Microb, Cell Fact, p 16 Fotiadis CI, Stoidis CN, Spyropoulos BG, Zografos ED (2008) Role of probiotics, prebiotics and synbiotics in chemoprevention for colorectal cancer. World J Gastroenterol 14:6453–6457 Dos Reis SA, da Conceição LL, Siqueira NP et al (2017) Review of the mechanisms of probiotic actions in the prevention of colorectal cancer. Nutr Res 37:1–19. https://doi.org/10.1016/j.nutres.2016.11.009 Ohkawara S, Furuya H, Nagashima K et al (2005) 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 135:2878–2883 Le Leu RK, Hu Y, Brown IL et al (2010) Synbiotic intervention of Bifidobacterium lactis and resistant starch protects against colorectal cancer development in rats. Carcinogenesis 31:246–251. https://doi.org/10.1093/carcin/bgp197 Ivanov II, Honda K (2012) Intestinal commensal microbes as immune modulators. Cell Host Microbe 12:496–508. https://doi.org/10.1016/j.chom.2012.09.009 Delcenserie V, Martel D, Lamoureux M et al (2008) Immunomodulatory effects of probiotics in the intestinal tract. Curr Issues Mol Biol 10:37–54 Pitt JM, Vétizou M, Waldschmitt N et al (2016) Fine-tuning cancer immunotherapy: optimizing the gut microbiome. Cancer Res 76:4602–4607 Honda K, Littman DR (2016) The microbiota in adaptive immune homeostasis and disease. Nature 535:75–84. https://doi.org/10.1038/nature18848 Kuo CH, Kuo CH, Wang SSW et al (2013) Long-term use of probiotic-containing yogurts is a safe way to prevent Helicobacter pylori: based on a Mongolian Gerbil’s model. Biochem Res Int. https://doi.org/10.1155/2013/594561 Chen X, Liu XM, Tian F et al (2012) Antagonistic activities of Lactobacilli against Helicobacter pylori growth and infection in human gastric epithelial cells. J Food Sci 77:9–14. https://doi.org/10.1111/j.1750-3841.2011.02498.x Oh Y, Osato MS, Han X et al (2002) Folk yoghurt kills Helicobacter pylori. J Appl Microbiol 93:1083–1088. https://doi.org/10.1046/j.1365-2672.2002.01779.x Verhoeven V, Renard N, Makar A et al (2013) Probiotics enhance the clearance of human papillomavirus-related cervical lesions: a prospective controlled pilot study. Eur J Cancer Prev 22:46–51. https://doi.org/10.1097/CEJ.0b013e328355ed23 Okawa T, Niibe H, Arai T et al (1993) Effect of LC9018 combined with radiation therapy on carcinoma of the uterine cervix. A phase III, multicenter, randomized, controlled study. Cancer 72:1949–1954 Bassaganya-Riera J, Viladomiu M, Pedragosa M et al (2012) Immunoregulatory mechanisms underlying prevention of colitis-associated colorectal cancer by probiotic bacteria. PLoS ONE 7:e34676. https://doi.org/10.1371/journal.pone.0034676 Mi H, Dong Y, Zhang B et al (2017) Bifidobacterium infantis ameliorates chemotherapy-induced intestinal mucositis via regulating T cell immunity in colorectal cancer rats. Cell Physiol Biochem 42:2330–2341. https://doi.org/10.1159/000480005 Viaud S, Saccheri F, Mignot G et al (2013) The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science 342:971–976. https://doi.org/10.1126/science.1240537 Iida N, Dzutsev A, Stewart CA et al (2013) Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science 342:967–970. https://doi.org/10.1126/science.1240527 Poutahidis T, Kleinewietfeld M, Erdman SE (2014) Gut microbiota and the paradox of cancer immunotherapy. Front Immunol 5:157. https://doi.org/10.3389/fimmu.2014.00157 West NR, Powrie F (2015) Immunotherapy not working? Check your microbiota. Cancer Cell 28:687–689 Wan MLY, El-Nezami H (2018) Targeting gut microbiota in hepatocellular carcinoma: probiotics as a novel therapy. Hepatobiliary Surg Nutr 7:11–20 Sivan A, Corrales L, Hubert N et al (2015) Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 350:1084–1089. https://doi.org/10.1126/science.aac4255 Vétizou M, Pitt JM, Daillère R et al (2015) Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350(6264):1079–1084. https://doi.org/10.1126/science.aad1329 Järvinen R, Knekt P, Hakulinen T, Aromaa A (2001) Prospective study on milk products, calcium and cancers of the colon and rectum. Eur J Clin Nutr 55:1000–1007. https://doi.org/10.1038/sj/ejcn/1601260 van’t Veer P, Goldbohm RA, van den Brandt PA, van’t Veer P (1994) Fermented dairy products, calcium, and colorectal cancer in the Netherlands Cohort Study. Cancer Res 54:3186–3190 Kearney J, Giovannucci E, Rimm EB et al (1996) Calcium, vitamin D, and dairy foods and the occurrence of colon cancer in men. Am J Epidemiol 143:907–917 Pietinen P, Malila N, Virtanen M et al (1999) Diet and risk of colorectal cancer in a cohort of Finnish men. Cancer Causes Control 10:387–396. https://doi.org/10.1023/A:1008962219408 Lin J, Zhang SM, Cook NR et al (2005) Intakes of calcium and vitamin D and risk of colorectal cancer in women. Am J Epidemiol 161:755–764. https://doi.org/10.1093/aje/kwi101 Larsson SC, Bergkvist L, Rutegård J et al (2006) Calcium and dairy food intakes are inversely associated with colorectal cancer risk in the Cohort of Swedish Men. Am J Clin Nutr 83:667–673 Aune D, Lau R, Chan DSM et al (2012) Dairy products and colorectal cancer risk: a systematic review and meta-analysis of cohort studies. Ann Oncol 23:37–45 Yang B, McCullough ML, Gapstur SM et al (2014) Calcium, vitamin D, dairy products, and mortality among colorectal cancer survivors: the cancer prevention study-II nutrition cohort. J Clin Oncol 32:2335–2343. https://doi.org/10.1200/JCO.2014.55.3024 Narisawa T, Reddy BS, Weisburger JH (1978) Effect of bile acids and dietary fat on large bowel carcinogenesis in animal models. Gastroenterol Jpn 13:206–212. https://doi.org/10.1007/BF02773665 Pala V, Sieri S, Berrino F et al (2011) Yogurt consumption and risk of colorectal cancer in the Italian European prospective investigation into cancer and nutrition cohort. Int J Cancer 129:2712–2719. https://doi.org/10.1002/ijc.26193 Sleator RD, Hill C (2008) Battle of the bugs. Science 321:1294–1295. https://doi.org/10.1126/science.321.5894.1294b Wells J (2011) Mucosal vaccination and therapy with genetically modified lactic acid bacteria. Annu Rev Food Sci Technol 2:423–445. https://doi.org/10.1146/annurev-food-022510-133640 Amalaradjou MAR, Bhunia AK (2013) Bioengineered probiotics, a strategic approach to control enteric infections. Bioengineered 4:379–387. https://doi.org/10.4161/bioe.23574 Steidler L, Hans W, Schotte L et al (2000) Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. Science 289:1352–1355 Zhuang Z, Wu Z-G, Chen M, Wang PG (2008) Secretion of human interferon-beta 1b by recombinant Lactococcus lactis. Biotechnol Lett 30:1819–1823. https://doi.org/10.1007/s10529-008-9761-y Pang Q, Ji Y, Li Y et al (2008) Intragastric administration with recombinant Lactococcus lactis producing heme oxygenase-1 prevents lipopolysaccharide-induced endotoxemia in rats. FEMS Microbiol Lett 283:62–68. https://doi.org/10.1111/j.1574-6968.2008.01141.x LeBlanc ADM, LeBlanc JG, Perdigón G et al (2008) Oral administration of a catalase-producing Lactococcus lactis can prevent a chemically induced colon cancer in mice. J Med Microbiol 57:100–105. https://doi.org/10.1099/jmm.0.47403-0 del Carmen S, de LeBlanc ADM, Levit R et al (2017) Anti-cancer effect of lactic acid bacteria expressing antioxidant enzymes or IL-10 in a colorectal cancer mouse model. Int Immunopharmacol 42:122–129. https://doi.org/10.1016/j.intimp.2016.11.017 Kajikawa A, Masuda K, Katoh M, Igimi S (2010) Adjuvant effects for oral immunization provided by recombinant Lactobacillus casei secreting biologically active murine interleukin-1β. Clin Vaccine Immunol 17:43–48. https://doi.org/10.1128/CVI.00337-09 Fredriksen L, Kleiveland CR, Hult LTO et al (2012) Surface display of N-terminally anchored invasin by Lactobacillus plantarum activates NF-κB in monocytes. Appl Environ Microbiol 78:5864–5871. https://doi.org/10.1128/AEM.01227-12 Wang Z, Yu Q, Gao J, Yang Q (2012) Mucosal and systemic immune responses induced by recombinant Lactobacillus spp. expressing the hemagglutinin of the avian influenza virus H5N1. Clin Vaccine Immunol 19:174–179. https://doi.org/10.1128/CVI.05618-11 Benbouziane B, Ribelles P, Aubry C et al (2013) Development of a stress-inducible controlled expression (SICE) system in Lactococcus lactis for the production and delivery of therapeutic molecules at mucosal surfaces. J Biotechnol 168:120–129. https://doi.org/10.1016/j.jbiotec.2013.04.019 Bermudez-Humaran LG, Cortes-Perez NG, Lefevre F et al (2005) 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 175:7297–7302. https://doi.org/10.4049/jimmunol.175.11.7297 Li Y, Li X, Liu H et al (2014) Intranasal immunization with recombinant lactococci carrying human papillomavirus E7 protein and mouse interleukin-12 DNA induces E7-specific antitumor effects in C57BL/6 mice. Oncol Lett 7:576–582. https://doi.org/10.3892/ol.2013.1743 Cortes-Perez NG, Bermúdez-Humarán LG, Le Loir Y et al (2003) Mice immunization with live lactococci displaying a surface anchored HPV-16 E7 oncoprotein. FEMS Microbiol Lett 229:37–42. https://doi.org/10.1016/S0378-1097(03)00778-X Rangel-Colmenero BR, Gomez-Gutierrez JG, Villatoro-Hernández J et al (2014) Enhancement of Ad-CRT/E7-mediated antitumor effect by preimmunization with L. lactis expressing HPV-16 E7. Viral Immunol 27:463–467. https://doi.org/10.1089/vim.2014.0055 Kitagawa K, Oda T, Saito H et al (2017) Development of oral cancer vaccine using recombinant Bifidobacterium displaying Wilms’ tumor 1 protein. Cancer Immunol Immunother 66:787–798. https://doi.org/10.1007/s00262-017-1984-0 Kimura NT, Taniguchi SI, Aoki K, Baba T (1980) Selective localization and growth of Bifidobacterium bifidum in mouse tumors following intravenous administration. Cancer Res 40:2061–2068 Yazawa K, Fujimori M, Nakamura T et al (2001) Bifidobacterium longum as a delivery system for gene therapy of chemically induced rat mammary tumors. Breast Cancer Res Treat 69:256. https://doi.org/10.1023/A:1010644217648 Fujimori M, Amano J, Taniguchi S (2002) The genus Bifidobacterium for cancer gene therapy. Curr Opin Drug Discov Dev 5:200–203 Sasaki T, Fujimori M, Hamaji Y et al (2006) Genetically engineered Bifidobacterium longum for tumor-targeting enzyme-prodrug therapy of autochthonous mammary tumors in rats. Cancer Sci 97:649–657. https://doi.org/10.1111/j.1349-7006.2006.00221.x Fujimori M (2006) Genetically engineered bifidobacterium as a drug delivery system for systemic therapy of metastatic breast cancer patients. Breast cancer 13:27–31. https://doi.org/10.2325/jbcs.13.27 Wei C, Xun AY, Wei XX et al (2015) Bifidobacteria expressing tumstatin protein for antitumor therapy in tumor-bearing mice. Technol Cancer Res Treat 15:498–508. https://doi.org/10.1177/1533034615581977 Fu G-F, Li X, Hou Y-Y et al (2005) Bifidobacterium longum as an oral delivery system of endostatin for gene therapy on solid liver cancer. Cancer Gene Ther 12:133–140. https://doi.org/10.1038/sj.cgt.7700758 Wang C, Ma Y, Hu Q et al (2016) Bifidobacterial recombinant thymidine kinase-ganciclovir gene therapy system induces FasL and TNFR2 mediated antitumor apoptosis in solid tumors. BMC Cancer 16:545. https://doi.org/10.1186/s12885-016-2608-3 Cano-Garrido O, Seras-Franzoso J, Garcia-Fruitós E (2015) Lactic acid bacteria: reviewing the potential of a promising delivery live vector for biomedical purposes. Microb Cell Fact 14:1–12. https://doi.org/10.1186/s12934-015-0313-6 Li W, Li C-B (2005) Effect of oral Lactococcus lactis containing endostatin on 1, 2-dimethylhydrazine-induced colon tumor in rats. World J Gastroenterol 11:7242–7247 Yi C, Huang Y, Guo Z, Wang S (2005) Antitumor effect of cytosine deaminase/5-fluorocytosine suicide gene therapy system mediated by Bifidobacterium infantis on melanoma. Acta Pharmacol Sin 26:629–634. https://doi.org/10.1111/j.1745-7254.2005.00094.x