Immunomodulatory effects of live and UV-killed Bacillus subtilis natto on inflammatory response in human colorectal adenocarcinoma cell line in vitro
,
Abstract
Background and Objectives: Colorectal cancer (CRC) is a heterogeneous disease of the colon or rectum arising from adenoma precursors and serrated polyps. Recently, probiotics have been proposed as an effective and potential therapeutic approach for CRC prevention and treatment. Probiotics have been shown to alleviate inflammation by restoring the integrity of the mucosal barrier and impeding cancer progression.
Materials and Methods: In this study, we aimed to investigate the immunomodulatory effects of live and UV-killed Bacillus subtilis natto on the inflammatory response in CRC. Caco-2 cells were exposed to various concentrations of live and UV-killed B. subtilis natto, and cell viability was assessed using MTT assay. Gene expression analysis of IL-10, TGF-β, TLR2 and TLR4 was performed using RT-qPCR.
Results: Our findings showed that both live and UV-killed B. subtilis natto caused significant reduction in inflammatory response by decreasing the gene expression of TLR2 and TLR4, and enhancing the gene expression of IL-10 and TGF-β in Caco-2 cells as compared to control group.
Conclusion: The results of this study suggest that live and UV-killed B. subtilis natto may hold potential as a therapeutic supplement for modulating inflammation in CRC.
1. Ciardiello F, Ciardiello D, Martini G, Napolitano S, Tabernero J, Cervantes A. Clinical management of metastatic colorectal cancer in the era of precision medicine. CA Cancer J Clin 2022; 72: 372-401.
2. Onyoh EF, Hsu W-F, Chang L-C, Lee Y-C, Wu M-S, Chiu H-M. The rise of colorectal cancer in Asia: epidemiology, screening, and management. Curr Gastroenterol Rep 2019; 21: 36.
3. Fong W, Li Q, Yu J. Gut microbiota modulation: a novel strategy for prevention and treatment of colorectal cancer. Oncogene 2020; 39: 4925-4943.
4. Kim J, Lee HK. Potential role of the gut microbiome in colorectal cancer progression. Front Immunol 2022; 12: 807648.
5. Schmitt M, Greten FR. The inflammatory pathogenesis of colorectal cancer. Nat Rev Immunol 2021; 21: 653-667.
6. Yao P, Tan F, Gao H, Wang L, Yang T, Cheng Y. Effects of probiotics on Toll-like receptor expression in ulcerative colitis rats induced by 2, 4, 6-trinitro-benzene sulfonic acid. Mol Med Rep 2017; 15: 1973-1980.
7. Klampfer L. Cytokines, inflammation and colon cancer. Curr Cancer Drug Targets 2011; 11: 451-464.
8. Johdi NA, Sukor NF. Colorectal cancer immunotherapy: options and strategies. Front Immunol 2020; 11: 1624.
9. Abedi Elkhichi P, Dabiri H, Nazemalhosseini Mojarad E, Rezasoltani S, Asadzadeh Aghdaei H, Pouriran R, et al. Prevalence of Helicobacter pylori in patients with colorectal cancer. Int J Mol Clin Microbiol 2018; 8: 1001-1005.
10. Buccafusca G, Proserpio I, Tralongo AC, Rametta Giuliano S, Tralongo P. Early colorectal cancer: diagnosis, treatment and survivorship care. Crit Rev Oncol Hematol 2019; 136: 20-30.
11. Miknevicius P, Zulpaite R, Leber B, Strupas K, Stiegler P, Schemmer P. The impact of probiotics on intestinal mucositis during chemotherapy for colorectal cancer: a comprehensive review of animal studies. Int J Mol Sci 2021; 22: 9347.
12. Eslami M, Yousefi B, Kokhaei P, Hemati M, Nejad ZR, Arabkari V, et al. Importance of probiotics in the prevention and treatment of colorectal cancer. J Cell Physiol 2019; 234: 17127-17143.
13. Molska M, Reguła J. Potential mechanisms of probiotics action in the prevention and treatment of colorectal cancer. Nutrients 2019; 11: 2453.
14. Ding S, Hu C, Fang J, Liu G. The protective role of probiotics against colorectal cancer. Oxid Med Cell Longev 2020; 2020: 8884583.
15. Mazkour S, Shekarforoush SS, Basiri S. The effects of supplementation of Bacillus subtilis and Bacillus coagulans spores on the intestinal microflora and growth performance in rat. Iran J Microbiol 2019; 11: 260-266.
16. Ruiz Sella SR, Bueno T, de Oliveira AAB, Karp SG, Soccol CR. Bacillus subtilis natto as a potential probiotic in animal nutrition. Crit Rev Biotechnol 2021; 41: 355-369.
17. Uesugi T, Mori S, Miyanaga K, Yamamoto N. GroEL secreted from Bacillus subtilis natto exerted a crucial role for anti-inflammatory IL-10 induction in THP-1 cells. Microorganisms 2023; 11: 1281.
18. Azimirad M, Alebouyeh M, Naji T. Inhibition of lipopolysaccharide-induced interleukin 8 in human adenocarcinoma cell line HT-29 by spore probiotics: B. coagulans and B. subtilis (natto). Probiotics Antimicrob Proteins 2017; 9: 56-63.
19. Adams CA. The probiotic paradox: live and dead cells are biological response modifiers. Nutr Res Rev 2010; 23: 37-46.
20. Keshavarz Azizi Raftar S, Ashrafian F, Yadegar A, Lari A, Moradi HR, Shahriary A, et al. The protective effects of live and pasteurized Akkermansia muciniphila and its extracellular vesicles against HFD/CCl4-induced liver injury. Microbiol Spectr 2021; 9 (2): e0048421.
21. Angélica Garrido‐Pereira M, Braga AL, Rocha AFd, Sampaio LA, Abreu PC. Effect of ultraviolet (UV) radiation on the abundance and respiration rates of probiotic bacteria. Aquac Res 2013; 44: 261-267.
22. Nabavi-Rad A, Jamshidizadeh S, Azizi M, Yadegar A, Robinson K, Monaghan TM, et al. The synergistic effect of levilactobacillus brevis IBRC-M10790 and vitamin D3 on Helicobacter pylori-induced inflammation. Front Cell Infect Microbiol 2023; 13: 1171469.
23. Paolillo R, Romano Carratelli C, Sorrentino S, Mazzola N, Rizzo A. Immunomodulatory effects of Lactobacillus plantarum on human colon cancer cells. Int Immunopharmacol 2009; 9: 1265-12671.
24. Wang S, Liu K, Seneviratne CJ, Li X, Cheung GS, Jin L, et al. Lipoteichoic acid from an Enterococcus faecalis clinical strain promotes TNF-α expression through the NF-κB and p38 MAPK signaling pathways in differentiated THP-1 macrophages. Biomed Rep 2015; 3: 697-702.
25. Li J, Lin S, Vanhoutte PM, Woo CW, Xu A. Akkermansia muciniphila protects against atherosclerosis by preventing metabolic endotoxemia-induced inflammation in Apoe−/− mice. Circulation 2016; 133: 2434-2446.
26. González-Domínguez É, Domínguez-Soto Á, Nieto C, Flores-Sevilla JL, Pacheco-Blanco M, Campos-Pena V, et al. Atypical activin A and IL-10 production impairs human CD16+ monocyte differentiation into anti-inflammatory macrophages. J Immunol 2016; 196: 1327-1337.
27. Ofinran O, Bose U, Hay D, Abdul S, Tufatelli C, Khan R. Selection of suitable reference genes for gene expression studies in normal human ovarian tissues, borderline ovarian tumours and ovarian cancer. Mol Med Rep 2016; 14: 5725-5731.
28. Xi Y, Xu P. Global colorectal cancer burden in 2020 and projections to 2040. Transl Oncol 2021; 14: 101174.
29. Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Prz Gastroenterol 2019; 14: 89-103.
30. Hua H, Sun Y, He X, Chen Y, Teng L, Lu C. Intestinal microbiota in colorectal adenoma-carcinoma sequence. Front Med (Lausanne) 2022; 9: 888340.
31. Dong J, Tai JW, Lu L-F. miRNA–Microbiota interaction in Gut Homeostasis and colorectal cancer. Trends Cancer 2019; 5: 666-669.
32. Gu S, Zaidi S, Hassan MI, Mohammad T, Malta TM, Noushmehr H, et al. Mutated CEACAMs disrupt transforming growth factor beta signaling and alter the intestinal microbiome to promote colorectal carcinogenesis. Gastroenterology 2020; 158: 238-252.
33. Kontomanolis EN, Koutras A, Syllaios A, Schizas D, Mastoraki A, Garmpis N, et al. Role of oncogenes and tumor-suppressor genes in carcinogenesis: a review. Anticancer Res 2020; 40: 6009-6015.
34. Drago L. Probiotics and colon cancer. Microorganisms 2019; 7: 66.
35. Kumar KS, Sastry N, Polaki H, Mishra V. Colon cancer prevention through probiotics: an overview. J Cancer Sci Ther 2015; 7: 81-92.
36. 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 2013; 65: 84-91.
37. Kim B-K, Yoon Y-S, Ryu Y, Chung M-J. Probiotic-derived p8 protein induce apoptosis via regulation of RNF152 in colorectal cancer cells. Am J Cancer Res 2021; 11: 746-759.
38. Yue Y, Wang S, Shi J, Xie Q, Li N, Guan J, et al. Effects of Lactobacillus acidophilus KLDS1. 0901 on proliferation and apoptosis of colon cancer cells. Front Microbiol 2022; 12: 788040.
39. Isazadeh A, Hajazimian S, Shadman B, Safaei S, Bedoustani AB, Chavoshi R, et al. Anti-cancer effects of probiotic Lactobacillus acidophilus for colorectal cancer cell line caco-2 through apoptosis induction. Pharm Sci 2021; 27: 262-267.
40. Saber A, Alipour B, Faghfoori Z, Mousavi Jam A, Yari Khosroushahi A. Secretion metabolites of probiotic yeast, Pichia kudriavzevii AS-12, induces apoptosis pathways in human colorectal cancer cell lines. Nutr Res 2017; 41: 36-46.
41. Keshavarz Azizi Raftar S, Abdollahiyan S, Azimirad M, Yadegar A, Vaziri F, Moshiri A, et al. The anti-fibrotic effects of heat-killed Akkermansia muciniphila MucT on liver fibrosis markers and activation of hepatic stellate cells. Probiotics Antimicrob Proteins 2021; 13: 776-787.
42. Kataria J, Li N, Wynn JL, Neu J. Probiotic microbes: do they need to be alive to be beneficial? Nutr Rev 2009; 67: 546-550.
43. Nagai T. Bacteriophages of Bacillus subtilis (natto) and their contamination in natto factories. Intech Open; 2012. https://doi.org/10.5772/33555
44. Zhang B, Chai J, He L, Dusanbieke M, Gong A. Nattokinase produced by natto fermentation with Bacillus subtilis inhibits breast cancer growth. Int J Clin Exp Med 2019; 12: 13380-13387.
45. Batlle E, Massagué J. Transforming growth factor-β signaling in immunity and cancer. Immunity 2019; 50: 924-940.
46. Daniel SG, Ball CL, Besselsen DG, Doetschman T, Hurwitz BL. Functional changes in the gut microbiome contribute to transforming growth factor β-deficient colon cancer. mSystems 2017; 2(5): e00065-17.
47. Xu X, Huang Q, Mao Y, Cui Z, Li Y, Huang Y, et al. Immunomodulatory effects of Bacillus subtilis (natto) B4 spores on murine macrophages. Microbiol Immunol 2012; 56: 817-824.
48. Fujii K, Kubo Y, Noguchi T, Tobita K. Effects of Bacillus subtilis natto strains on antiviral responses in Resiquimod-Stimulated human M1-Phenotype macrophages. Foods 2023; 12: 313.
49. Magri A, Oliveira M, Baldo C, Tischer C, Sartori D, Mantovani MS, et al. Production of fructooligosaccharides by Bacillus subtilis natto CCT7712 and their antiproliferative potential. J Appl Microbiol 2020; 128: 1414-1426.
50. Beilmann-Lehtonen I, Böckelman C, Mustonen H, Koskensalo S, Hagström J, Haglund C. The prognostic role of tissue TLR2 and TLR4 in colorectal cancer. Virchows Arch 2020; 477: 705-715.
51. Li T-T, Ogino S, Qian ZR. Toll-like receptor signaling in colorectal cancer: carcinogenesis to cancer therapy. World J Gastroenterol 2014; 20: 17699-17708.
52. Pastille E, Faßnacht T, Adamczyk A, Ngo Thi Phuong N, Buer J, Westendorf AM. Inhibition of TLR4 signaling impedes tumor growth in colitis-associated colon cancer. Front Immunol 2021; 12: 669747.
53. Meng S, Li Y, Zang X, Jiang Z, Ning H, Li J. Effect of TLR2 on the proliferation of inflammation-related colorectal cancer and sporadic colorectal cancer. Cancer Cell Int 2020; 20: 95.
54. Li Y, Yang S, Lun J, Gao J, Gao X, Gong Z, et al. Inhibitory effects of the Lactobacillus rhamnosus GG effector protein HM0539 on inflammatory response through the TLR4/MyD88/NF-кB axis. Front Immunol 2020; 11: 551449.
55. Li M, Liu P, Wang B, Zhou J, Yang J. Inhibition of nuclear factor Kappa B as a therapeutic target for lung cancer. Altern Ther Health Med 2022; 28: 44-51.
56. Sharma RK, Otsuka M, Gaba G, Mehta S. Inhibitors of transcription factor nuclear factor-kappa beta (NF-κβ)-DNA binding. RSC Adv 2013; 3: 1282-1296.
57. Slattery ML, Mullany LE, Sakoda L, Samowitz WS, Wolff RK, Stevens JR, et al. The NF-κB signalling pathway in colorectal cancer: associations between dysregulated gene and miRNA expression. J Cancer Res Clin Oncol 2018; 144: 269-283.
58. Sun R, Niu H, Sun M, Miao X, Jin X, Xu X, et al. Effects of Bacillus subtilis natto JLCC513 on gut microbiota and intestinal barrier function in obese rats. J Appl Microbiol 2022; 133: 3634-3644.
59. Tobita K, Meguro R. Bacillus subtilis BN strain promotes Th1 response via Toll‐like receptor 2 in polarized mouse M1 macrophage. J Food Biochem 2022; 46(2): e14046.
60. Nasiri G, Azimirad M, Goudarzi H, Amirkamali S, Yadegar A, Ghalavand Z, et al. The inhibitory effects of live and UV-killed Akkermansia muciniphila and its derivatives on cytotoxicity and inflammatory response induced by Clostridioides difficile RT001 in vitro. Int Microbiol 2024; 27: 393-409.
61. Shi M, Yue Y, Ma C, Dong L, Chen F. Pasteurized Akkermansia muciniphila ameliorate the LPS-induced intestinal barrier dysfunction via modulating AMPK and NF-κB through TLR2 in Caco-2 cells. Nutrients 2022; 14: 764.
2. Onyoh EF, Hsu W-F, Chang L-C, Lee Y-C, Wu M-S, Chiu H-M. The rise of colorectal cancer in Asia: epidemiology, screening, and management. Curr Gastroenterol Rep 2019; 21: 36.
3. Fong W, Li Q, Yu J. Gut microbiota modulation: a novel strategy for prevention and treatment of colorectal cancer. Oncogene 2020; 39: 4925-4943.
4. Kim J, Lee HK. Potential role of the gut microbiome in colorectal cancer progression. Front Immunol 2022; 12: 807648.
5. Schmitt M, Greten FR. The inflammatory pathogenesis of colorectal cancer. Nat Rev Immunol 2021; 21: 653-667.
6. Yao P, Tan F, Gao H, Wang L, Yang T, Cheng Y. Effects of probiotics on Toll-like receptor expression in ulcerative colitis rats induced by 2, 4, 6-trinitro-benzene sulfonic acid. Mol Med Rep 2017; 15: 1973-1980.
7. Klampfer L. Cytokines, inflammation and colon cancer. Curr Cancer Drug Targets 2011; 11: 451-464.
8. Johdi NA, Sukor NF. Colorectal cancer immunotherapy: options and strategies. Front Immunol 2020; 11: 1624.
9. Abedi Elkhichi P, Dabiri H, Nazemalhosseini Mojarad E, Rezasoltani S, Asadzadeh Aghdaei H, Pouriran R, et al. Prevalence of Helicobacter pylori in patients with colorectal cancer. Int J Mol Clin Microbiol 2018; 8: 1001-1005.
10. Buccafusca G, Proserpio I, Tralongo AC, Rametta Giuliano S, Tralongo P. Early colorectal cancer: diagnosis, treatment and survivorship care. Crit Rev Oncol Hematol 2019; 136: 20-30.
11. Miknevicius P, Zulpaite R, Leber B, Strupas K, Stiegler P, Schemmer P. The impact of probiotics on intestinal mucositis during chemotherapy for colorectal cancer: a comprehensive review of animal studies. Int J Mol Sci 2021; 22: 9347.
12. Eslami M, Yousefi B, Kokhaei P, Hemati M, Nejad ZR, Arabkari V, et al. Importance of probiotics in the prevention and treatment of colorectal cancer. J Cell Physiol 2019; 234: 17127-17143.
13. Molska M, Reguła J. Potential mechanisms of probiotics action in the prevention and treatment of colorectal cancer. Nutrients 2019; 11: 2453.
14. Ding S, Hu C, Fang J, Liu G. The protective role of probiotics against colorectal cancer. Oxid Med Cell Longev 2020; 2020: 8884583.
15. Mazkour S, Shekarforoush SS, Basiri S. The effects of supplementation of Bacillus subtilis and Bacillus coagulans spores on the intestinal microflora and growth performance in rat. Iran J Microbiol 2019; 11: 260-266.
16. Ruiz Sella SR, Bueno T, de Oliveira AAB, Karp SG, Soccol CR. Bacillus subtilis natto as a potential probiotic in animal nutrition. Crit Rev Biotechnol 2021; 41: 355-369.
17. Uesugi T, Mori S, Miyanaga K, Yamamoto N. GroEL secreted from Bacillus subtilis natto exerted a crucial role for anti-inflammatory IL-10 induction in THP-1 cells. Microorganisms 2023; 11: 1281.
18. Azimirad M, Alebouyeh M, Naji T. Inhibition of lipopolysaccharide-induced interleukin 8 in human adenocarcinoma cell line HT-29 by spore probiotics: B. coagulans and B. subtilis (natto). Probiotics Antimicrob Proteins 2017; 9: 56-63.
19. Adams CA. The probiotic paradox: live and dead cells are biological response modifiers. Nutr Res Rev 2010; 23: 37-46.
20. Keshavarz Azizi Raftar S, Ashrafian F, Yadegar A, Lari A, Moradi HR, Shahriary A, et al. The protective effects of live and pasteurized Akkermansia muciniphila and its extracellular vesicles against HFD/CCl4-induced liver injury. Microbiol Spectr 2021; 9 (2): e0048421.
21. Angélica Garrido‐Pereira M, Braga AL, Rocha AFd, Sampaio LA, Abreu PC. Effect of ultraviolet (UV) radiation on the abundance and respiration rates of probiotic bacteria. Aquac Res 2013; 44: 261-267.
22. Nabavi-Rad A, Jamshidizadeh S, Azizi M, Yadegar A, Robinson K, Monaghan TM, et al. The synergistic effect of levilactobacillus brevis IBRC-M10790 and vitamin D3 on Helicobacter pylori-induced inflammation. Front Cell Infect Microbiol 2023; 13: 1171469.
23. Paolillo R, Romano Carratelli C, Sorrentino S, Mazzola N, Rizzo A. Immunomodulatory effects of Lactobacillus plantarum on human colon cancer cells. Int Immunopharmacol 2009; 9: 1265-12671.
24. Wang S, Liu K, Seneviratne CJ, Li X, Cheung GS, Jin L, et al. Lipoteichoic acid from an Enterococcus faecalis clinical strain promotes TNF-α expression through the NF-κB and p38 MAPK signaling pathways in differentiated THP-1 macrophages. Biomed Rep 2015; 3: 697-702.
25. Li J, Lin S, Vanhoutte PM, Woo CW, Xu A. Akkermansia muciniphila protects against atherosclerosis by preventing metabolic endotoxemia-induced inflammation in Apoe−/− mice. Circulation 2016; 133: 2434-2446.
26. González-Domínguez É, Domínguez-Soto Á, Nieto C, Flores-Sevilla JL, Pacheco-Blanco M, Campos-Pena V, et al. Atypical activin A and IL-10 production impairs human CD16+ monocyte differentiation into anti-inflammatory macrophages. J Immunol 2016; 196: 1327-1337.
27. Ofinran O, Bose U, Hay D, Abdul S, Tufatelli C, Khan R. Selection of suitable reference genes for gene expression studies in normal human ovarian tissues, borderline ovarian tumours and ovarian cancer. Mol Med Rep 2016; 14: 5725-5731.
28. Xi Y, Xu P. Global colorectal cancer burden in 2020 and projections to 2040. Transl Oncol 2021; 14: 101174.
29. Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Prz Gastroenterol 2019; 14: 89-103.
30. Hua H, Sun Y, He X, Chen Y, Teng L, Lu C. Intestinal microbiota in colorectal adenoma-carcinoma sequence. Front Med (Lausanne) 2022; 9: 888340.
31. Dong J, Tai JW, Lu L-F. miRNA–Microbiota interaction in Gut Homeostasis and colorectal cancer. Trends Cancer 2019; 5: 666-669.
32. Gu S, Zaidi S, Hassan MI, Mohammad T, Malta TM, Noushmehr H, et al. Mutated CEACAMs disrupt transforming growth factor beta signaling and alter the intestinal microbiome to promote colorectal carcinogenesis. Gastroenterology 2020; 158: 238-252.
33. Kontomanolis EN, Koutras A, Syllaios A, Schizas D, Mastoraki A, Garmpis N, et al. Role of oncogenes and tumor-suppressor genes in carcinogenesis: a review. Anticancer Res 2020; 40: 6009-6015.
34. Drago L. Probiotics and colon cancer. Microorganisms 2019; 7: 66.
35. Kumar KS, Sastry N, Polaki H, Mishra V. Colon cancer prevention through probiotics: an overview. J Cancer Sci Ther 2015; 7: 81-92.
36. 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 2013; 65: 84-91.
37. Kim B-K, Yoon Y-S, Ryu Y, Chung M-J. Probiotic-derived p8 protein induce apoptosis via regulation of RNF152 in colorectal cancer cells. Am J Cancer Res 2021; 11: 746-759.
38. Yue Y, Wang S, Shi J, Xie Q, Li N, Guan J, et al. Effects of Lactobacillus acidophilus KLDS1. 0901 on proliferation and apoptosis of colon cancer cells. Front Microbiol 2022; 12: 788040.
39. Isazadeh A, Hajazimian S, Shadman B, Safaei S, Bedoustani AB, Chavoshi R, et al. Anti-cancer effects of probiotic Lactobacillus acidophilus for colorectal cancer cell line caco-2 through apoptosis induction. Pharm Sci 2021; 27: 262-267.
40. Saber A, Alipour B, Faghfoori Z, Mousavi Jam A, Yari Khosroushahi A. Secretion metabolites of probiotic yeast, Pichia kudriavzevii AS-12, induces apoptosis pathways in human colorectal cancer cell lines. Nutr Res 2017; 41: 36-46.
41. Keshavarz Azizi Raftar S, Abdollahiyan S, Azimirad M, Yadegar A, Vaziri F, Moshiri A, et al. The anti-fibrotic effects of heat-killed Akkermansia muciniphila MucT on liver fibrosis markers and activation of hepatic stellate cells. Probiotics Antimicrob Proteins 2021; 13: 776-787.
42. Kataria J, Li N, Wynn JL, Neu J. Probiotic microbes: do they need to be alive to be beneficial? Nutr Rev 2009; 67: 546-550.
43. Nagai T. Bacteriophages of Bacillus subtilis (natto) and their contamination in natto factories. Intech Open; 2012. https://doi.org/10.5772/33555
44. Zhang B, Chai J, He L, Dusanbieke M, Gong A. Nattokinase produced by natto fermentation with Bacillus subtilis inhibits breast cancer growth. Int J Clin Exp Med 2019; 12: 13380-13387.
45. Batlle E, Massagué J. Transforming growth factor-β signaling in immunity and cancer. Immunity 2019; 50: 924-940.
46. Daniel SG, Ball CL, Besselsen DG, Doetschman T, Hurwitz BL. Functional changes in the gut microbiome contribute to transforming growth factor β-deficient colon cancer. mSystems 2017; 2(5): e00065-17.
47. Xu X, Huang Q, Mao Y, Cui Z, Li Y, Huang Y, et al. Immunomodulatory effects of Bacillus subtilis (natto) B4 spores on murine macrophages. Microbiol Immunol 2012; 56: 817-824.
48. Fujii K, Kubo Y, Noguchi T, Tobita K. Effects of Bacillus subtilis natto strains on antiviral responses in Resiquimod-Stimulated human M1-Phenotype macrophages. Foods 2023; 12: 313.
49. Magri A, Oliveira M, Baldo C, Tischer C, Sartori D, Mantovani MS, et al. Production of fructooligosaccharides by Bacillus subtilis natto CCT7712 and their antiproliferative potential. J Appl Microbiol 2020; 128: 1414-1426.
50. Beilmann-Lehtonen I, Böckelman C, Mustonen H, Koskensalo S, Hagström J, Haglund C. The prognostic role of tissue TLR2 and TLR4 in colorectal cancer. Virchows Arch 2020; 477: 705-715.
51. Li T-T, Ogino S, Qian ZR. Toll-like receptor signaling in colorectal cancer: carcinogenesis to cancer therapy. World J Gastroenterol 2014; 20: 17699-17708.
52. Pastille E, Faßnacht T, Adamczyk A, Ngo Thi Phuong N, Buer J, Westendorf AM. Inhibition of TLR4 signaling impedes tumor growth in colitis-associated colon cancer. Front Immunol 2021; 12: 669747.
53. Meng S, Li Y, Zang X, Jiang Z, Ning H, Li J. Effect of TLR2 on the proliferation of inflammation-related colorectal cancer and sporadic colorectal cancer. Cancer Cell Int 2020; 20: 95.
54. Li Y, Yang S, Lun J, Gao J, Gao X, Gong Z, et al. Inhibitory effects of the Lactobacillus rhamnosus GG effector protein HM0539 on inflammatory response through the TLR4/MyD88/NF-кB axis. Front Immunol 2020; 11: 551449.
55. Li M, Liu P, Wang B, Zhou J, Yang J. Inhibition of nuclear factor Kappa B as a therapeutic target for lung cancer. Altern Ther Health Med 2022; 28: 44-51.
56. Sharma RK, Otsuka M, Gaba G, Mehta S. Inhibitors of transcription factor nuclear factor-kappa beta (NF-κβ)-DNA binding. RSC Adv 2013; 3: 1282-1296.
57. Slattery ML, Mullany LE, Sakoda L, Samowitz WS, Wolff RK, Stevens JR, et al. The NF-κB signalling pathway in colorectal cancer: associations between dysregulated gene and miRNA expression. J Cancer Res Clin Oncol 2018; 144: 269-283.
58. Sun R, Niu H, Sun M, Miao X, Jin X, Xu X, et al. Effects of Bacillus subtilis natto JLCC513 on gut microbiota and intestinal barrier function in obese rats. J Appl Microbiol 2022; 133: 3634-3644.
59. Tobita K, Meguro R. Bacillus subtilis BN strain promotes Th1 response via Toll‐like receptor 2 in polarized mouse M1 macrophage. J Food Biochem 2022; 46(2): e14046.
60. Nasiri G, Azimirad M, Goudarzi H, Amirkamali S, Yadegar A, Ghalavand Z, et al. The inhibitory effects of live and UV-killed Akkermansia muciniphila and its derivatives on cytotoxicity and inflammatory response induced by Clostridioides difficile RT001 in vitro. Int Microbiol 2024; 27: 393-409.
61. Shi M, Yue Y, Ma C, Dong L, Chen F. Pasteurized Akkermansia muciniphila ameliorate the LPS-induced intestinal barrier dysfunction via modulating AMPK and NF-κB through TLR2 in Caco-2 cells. Nutrients 2022; 14: 764.
| Files | ||
| Issue | Vol 16 No 4 (2024) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v16i4.16301 | |
| Keywords | ||
| Bacillus subtilis; Probiotics; Gene expression; Colorectal neoplasms; Immunomodulation | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Abedi Elkhichi P, Aslanimehr M, Javadi A, Yadegar A. Immunomodulatory effects of live and UV-killed Bacillus subtilis natto on inflammatory response in human colorectal adenocarcinoma cell line in vitro. Iran J Microbiol. 2024;16(4):434-442.
