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Gut microbiota in cancer: insights on microbial metabolites and therapeutic strategies

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Abstract

In recent years, the role of gut microbiota in cancer treatment has attracted substantial attention. It is now well established that gut microbiota and its metabolites significantly contribute to the incidence, treatment, and prognosis of various cancers. This review provides a comprehensive review on the pivotal role of gut microbiota and their metabolites in cancer initiation and progression. Furthermore, it evaluates the impact of gut microbiota on the efficacy and associated side effects of anticancer therapies, including radiotherapy, chemotherapy, and immunotherapy, thus emphasizing the clinical importance of gut microbiota reconstitution in cancer treatment.

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References

  1. Brown EM, Sadarangani M, Finlay BB. The role of the immune system in governing host microbe interactions in the intestine. Nat Immunol. 2013;14(7):660–7. https://doi.org/10.1038/ni.2611.

    Article  CAS  PubMed  Google Scholar 

  2. Garrett WS. Cancer and the microbiota. Science. 2015;348(6230):80–6. https://doi.org/10.1126/science.aaa4972.

    Article  CAS  PubMed Central  Google Scholar 

  3. Sepich-Poore GD, Zitvogel L, Straussman R, Hasty J, Wargo JA, Knight R. The microbiome and human cancer. Science. 2021;371(6536):eabc4552. https://doi.org/10.1126/science.abc4552.

    Article  CAS  PubMed Central  Google Scholar 

  4. Zhang W, An Y, Qin X, Wu X, Wang X, Hou H, et al. Gut microbiota-derived metabolites in colorectal cancer: the bad and the challenges. Front Oncol. 2021;18(11):739648. https://doi.org/10.3389/fonc.2021.739648.

    Article  CAS  Google Scholar 

  5. Sędzikowska A, Szablewski L. Human gut microbiota in health and selected cancers. Int J Mol Sci. 2021;22(24):13440. https://doi.org/10.3390/ijms222413440.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Zyoud SH, Al-Jabi SW, Amer R, Shakhshir M, Shahwan M, Jairoun AA, et al. Global research trends on the links between the gut microbiome and cancer: a visualization analysis. J Transl Med. 2022;20(1):83. https://doi.org/10.1186/s12967-022-03293-y.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Chen C-C, Liou J-M, Lee Y-C, Hong T-C, El-Omar EM, Wu M-S. The interplay between Helicobacter pylori and gastrointestinal microbiota. Gut Microbes. 2021;13(1):1–22. https://doi.org/10.1080/19490976.2021.1909459.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Jaye K, Li CG, Chang D, Bhuyan DJ. The role of key gut microbial metabolites in the development and treatment of cancer. Gut Microbes. 2022;14(1):2038865. https://doi.org/10.1080/19490976.2022.2038865.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Yang Q, Wang B, Zheng Q, Li H, Meng X, Zhou F, et al. A review of gut microbiota-derived meabolites in tumor progression and cancer therapy. Adv Sci Weinh Baden-Wurtt Ger. 2023;10(15):e2207366. https://doi.org/10.1002/advs.202207366.

    Article  CAS  Google Scholar 

  10. Deleu S, Machiels K, Raes J, Verbeke K, Vermeire S. Short chain fatty acids and its producing organisms: an overlooked therapy for IBD? EBioMedicine. 2021;66:103293. https://doi.org/10.1016/j.ebiom.2021.103293.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Rangan P, Mondino A. Microbial short-chain fatty acids: a strategy to tune adoptive T cell therapy. J Immunother Cancer. 2022;10(7):e004147. https://doi.org/10.1136/jitc-2021-004147.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Gomes S, Rodrigues AC, Pazienza V, Preto A. Modulation of the tumor microenvironment by microbiota-derived short-chain fatty acids: impact in colorectal cancer therapy. Int J Mol Sci. 2023;24(6):5069. https://doi.org/10.3390/ijms24065069.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hou H, Chen D, Zhang K, Zhang W, Liu T, Wang S, et al. Gut microbiota-derived short-chain fatty acids and colorectal cancer: ready for clinical translation? Cancer Lett. 2022;526:225–35. https://doi.org/10.1016/j.canlet.2021.11.027.

    Article  CAS  PubMed  Google Scholar 

  14. Geng H-W, Yin F-Y, Zhang Z-F, Gong X, Yang Y. Butyrate suppresses glucose metabolism of colorectal cancer cells via gpr109a-akt signaling pathway and enhances chemotherapy. Front Mol Biosci. 2021;8:634874. https://doi.org/10.3389/fmolb.2021.634874.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Huo R-X, Wang Y-J, Hou S-B, Wang W, Zhang C-Z, Wan X-H. Gut mucosal microbiota profiles linked to colorectal cancer recurrence. World J Gastroenterol. 2022;28(18):1946–64. https://doi.org/10.3748/wjg.v28.i18.1946.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Coutzac C, Jouniaux J-M, Paci A, Schmidt J, Mallardo D, Seck A, et al. Systemic short chain fatty acids limit antitumor effect of CTLA-4 blockade in hosts with cancer. Nat Commun. 2020;11(1):2168. https://doi.org/10.1038/s41467-020-16079-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Panebianco C, Villani A, Pisati F, Orsenigo F, Ulaszewska M, Latiano TP, et al. Butyrate, a postbiotic of intestinal bacteria, affects pancreatic cancer and gemcitabine response in in vitro and in vivo models. Biomed Pharmacother Biomedecine Pharmacother. 2022;151:113163. https://doi.org/10.1016/j.biopha.2022.113163.

    Article  CAS  Google Scholar 

  18. Sanaei M, Kavoosi F. Effect of sodium butyrate on p16INK4a, p14ARF, p15INK4b, class I HDACs (HDACs 1, 2, 3) class II HDACs (HDACs 4, 5, 6), cell growth inhibition and apoptosis induction in pancreatic cancer AsPC-1 and colon cancer HCT-116 cell lines. Asian Pac J Cancer Prev. 2022;23(3):795–802. https://doi.org/10.31557/APJCP.2022.23.3.795.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Louis P, Hold GL, Flint HJ. The gut microbiota, bacterial metabolites and colorectal cancer. Nat Rev Microbiol. 2014;12(10):661–72. https://doi.org/10.1038/nrmicro3344.

    Article  CAS  PubMed  Google Scholar 

  20. Donohoe DR, Collins LB, Wali A, Bigler R, Sun W, Bultman SJ. The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. Mol Cell. 2012;48(4):612–26. https://doi.org/10.1016/j.molcel.2012.08.033.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Okumura S, Konishi Y, Narukawa M, Sugiura Y, Yoshimoto S, Arai Y, et al. Gut bacteria identified in colorectal cancer patients promote tumourigenesis via butyrate secretion. Nat Commun. 2021;12(1):5674. https://doi.org/10.1038/s41467-021-25965-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Belcheva A, Irrazabal T, Robertson SJ, Streutker C, Maughan H, Rubino S, et al. Gut microbial metabolism drives transformation of MSH2-deficient colon epithelial cells. Cell. 2014;158(2):288–99. https://doi.org/10.1016/j.cell.2014.04.051.

    Article  CAS  Google Scholar 

  23. Dicks LMT, Dreyer L, Smith C, van Staden AD. A review: the fate of bacteriocins in the human gastro-intestinal tract: do they cross the gut-blood barrier? Front Microbiol. 2018;9:2297. https://doi.org/10.3389/fmicb.2018.02297.

    Article  PubMed Central  Google Scholar 

  24. Dobson A, Cotter PD, Ross RP, Hill C. Bacteriocin production: a probiotic trait? Appl Environ Microbiol. 2012;78(1):1–6. https://doi.org/10.1128/AEM.05576-11.

    Article  CAS  PubMed Central  Google Scholar 

  25. Riboulet-Bisson E, Sturme MHJ, Jeffery IB, O’Donnell MM, Neville BA, Forde BM, et al. Effect of Lactobacillus salivarius bacteriocin Abp118 on the mouse and pig intestinal microbiota. PLoS ONE. 2012;7(2):e31113. https://doi.org/10.1371/journal.pone.0031113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kim T-S, Hur J-W, Yu M-A, Cheigh C-I, Kim K-N, Hwang J-K, et al. Antagonism of Helicobacter pylori by bacteriocins of lactic acid bacteria. J Food Prot. 2003;66(1):3–12. https://doi.org/10.4315/0362-028x-66.1.3.

    Article  CAS  PubMed  Google Scholar 

  27. Maher S, McClean S. Investigation of the cytotoxicity of eukaryotic and prokaryotic antimicrobial peptides in intestinal epithelial cells in vitro. Biochem Pharmacol. 2006;71(9):1289–98. https://doi.org/10.1016/j.bcp.2006.01.012.

    Article  CAS  PubMed  Google Scholar 

  28. Balcik-Ercin P, Sever B. An investigation of bacteriocin nisin anti-cancer effects and FZD7 protein interactions in liver cancer cells. Chem Biol Interact. 2022;366:110152. https://doi.org/10.1016/j.cbi.2022.110152.

    Article  CAS  PubMed  Google Scholar 

  29. Kaur J, Raza K, Preet S. Organogel mediated co-delivery of nisin and 5-fluorouracil: a synergistic approach against skin cancer. J Microencapsul. 2022;39(7–8):609–25. https://doi.org/10.1080/02652048.2022.2149871.

    Article  CAS  PubMed  Google Scholar 

  30. Patil SM, Barji DS, Aziz S, McChesney DA, Bagde S, Muttil P, et al. Pulmonary delivery of spray-dried Nisin ZP antimicrobial peptide for non-small cell lung cancer (NSCLC) treatment. Int J Pharm. 2023;634:122641. https://doi.org/10.1016/j.ijpharm.2023.122641.

    Article  CAS  PubMed  Google Scholar 

  31. Joo NE, Ritchie K, Kamarajan P, Miao D, Kapila YL. Nisin, an apoptogenic bacteriocin and food preservative, attenuates HNSCC tumorigenesis via CHAC1. Cancer Med. 2012;1(3):295–305. https://doi.org/10.1002/cam4.35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Preet S, Bharati S, Panjeta A, Tewari R, Rishi P. Effect of nisin and doxorubicin on DMBA-inducedskin carcinogenesis—a possible adjunct therapy. Tumour Biol J Int Soc Oncodevelopmental Biol Med. 2015;36(11):8301–8. https://doi.org/10.1007/s13277-015-3571-3.

    Article  CAS  Google Scholar 

  33. Avand A, Akbari V, Shafizadegan S. In vitro cytotoxic activity of a lactococcus lactis antimicrobial peptide against breast cancer cells. Iran J Biotechnol. 2018;16(3):e1867. https://doi.org/10.15171/ijb.1867.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Duboc H, Rajca S, Rainteau D, Benarous D, Maubert M-A, Quervain E, et al. Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases. Gut. 2013;62(4):531–9. https://doi.org/10.1136/gutjnl-2012-302578.

    Article  CAS  PubMed  Google Scholar 

  35. Kriaa A, Mariaule V, Jablaoui A, Rhimi S, Mkaouar H, Hernandez J, et al. Bile acids: key players in inflammatory bowel diseases? Cells. 2022;11(5):901. https://doi.org/10.3390/cells11050901.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Bernstein C, Holubec H, Bhattacharyya AK, Nguyen H, Payne CM, Zaitlin B, et al. Carcinogenicity of deoxycholate, a secondary bile acid. Arch Toxicol. 2011;85(8):863–71. https://doi.org/10.1007/s00204-011-0648-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Liu L, Dong W, Wang S, Zhang Y, Liu T, Xie R, et al. Deoxycholic acid disrupts the intestinal mucosal barrier and promotes intestinal tumorigenesis. Food Funct. 2018;9(11):5588–97. https://doi.org/10.1039/c8fo01143e.

    Article  CAS  PubMed  Google Scholar 

  38. Payne CM, Weber C, Crowley-Skillicorn C, Dvorak K, Bernstein H, Bernstein C, et al. Deoxycholate induces mitochondrial oxidative stress and activates NF-kappaB through multiple mechanisms in HCT-116 colon epithelial cells. Carcinogenesis. 2007;28(1):215–22. https://doi.org/10.1093/carcin/bgl139.

    Article  CAS  PubMed  Google Scholar 

  39. Jin D, Huang K, Xu M, Hua H, Ye F, Yan J, et al. Deoxycholic acid induces gastric intestinal metaplasia by activating STAT3 signaling and disturbing gastric bile acids metabolism and microbiota. Gut Microbes. 2022;14(1):2120744. https://doi.org/10.1080/19490976.2022.2120744.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ocvirk S, O’Keefe SJD. Dietary fat, bile acid metabolism and colorectal cancer. Semin Cancer Biol. 2021;73:347–55. https://doi.org/10.1016/j.semcancer.2020.10.003.

    Article  CAS  PubMed  Google Scholar 

  41. Hang S, Paik D, Yao L, Kim E, Trinath J, Lu J, et al. Author correction: bile acid metabolites control TH17 and Treg cell differentiation. Nature. 2020;579(7798):E7. https://doi.org/10.1038/s41586-020-2030-5.

    Article  CAS  PubMed  Google Scholar 

  42. Liu T, Song X, Khan S, Li Y, Guo Z, Li C, et al. The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: an old story, yet mesmerizing. Int J Cancer. 2020;146:1780–90. https://doi.org/10.1002/ijc.32563.

    Article  CAS  PubMed  Google Scholar 

  43. Nguyen TT, Ung TT, Kim NH, Jung YD. Role of bile acids in colon carcinogenesis. World J Clin Cases. 2018;6(13):577–88. https://doi.org/10.12998/wjcc.v6.i13.577.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Mima K, Kosumi K, Baba Y, Hamada T, Baba H, Ogino S. The microbiome, genetics, and gastrointestinal neoplasms: the evolving field of molecular pathological epidemiology to analyze the tumor-immune-microbiome interaction. Hum Genet. 2021;140(5):725–46. https://doi.org/10.1007/s00439-020-02235-2.

    Article  PubMed  Google Scholar 

  45. Yoshimoto S, Loo TM, Atarashi K, Kanda H, Sato S, Oyadomari S, et al. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature. 2013;499(7456):97–101. https://doi.org/10.1038/nature12347.

    Article  CAS  PubMed  Google Scholar 

  46. Goldberg AA, Titorenko VI, Beach A, Sanderson JT. Bile acids induce apoptosis selectively in androgen-dependent and -independent prostate cancer cells. PeerJ. 2013;1:e122. https://doi.org/10.7717/peerj.122.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Mikó E, Vida A, Kovács T, Ujlaki G, Trencsényi G, Márton J, et al. Lithocholic acid, a bacterial metabolite reduces breast cancer cell proliferation and aggressiveness. Biochim Biophys Acta Bioenerg. 2018;1859(9):958–74. https://doi.org/10.1016/j.bbabio.2018.04.002.

    Article  CAS  PubMed  Google Scholar 

  48. Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH, et al. Guidelines for diagnosis, treatment, and prevention of clostridium difficile infections. Am J Gastroenterol. 2013;108(4):478–98. https://doi.org/10.1038/ajg.2013.4.

    Article  CAS  PubMed  Google Scholar 

  49. Wang Y, Zhang S, Borody TJ, Zhang F. Encyclopedia of fecal microbiota transplantation: a review of effectiveness in the treatment of 85 diseases. Chin Med J (Engl). 2022;135(16):1927–39. https://doi.org/10.1097/CM9.0000000000002339.

    Article  PubMed  Google Scholar 

  50. Lu G, Wang W, Li P, Wen Q, Cui B, Zhang F. Washed preparation of faecal microbiota changes the transplantation related safety, quantitative method and delivery. Microb Biotechnol. 2022;15(9):2439–49. https://doi.org/10.1111/1751-7915.14074.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Marcella C, Cui B, Kelly CR, Ianiro G, Cammarota G, Zhang F. Systematic review: the global incidence of faecal microbiota transplantation-related adverse events from 2000 to 2020. Aliment Pharmacol Ther. 2021;53(1):33–42. https://doi.org/10.1111/apt.16148.

    Article  PubMed  Google Scholar 

  52. Rosshart SP, Vassallo BG, Angeletti D, Hutchinson DS, Morgan AP, Takeda K, et al. Wild mouse gut microbiota promotes host fitness and improves disease resistance. Cell. 2017;171(5):1015-1028.e13. https://doi.org/10.1016/j.cell.2017.09.016.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Wong SH, Zhao L, Zhang X, Nakatsu G, Han J, Xu W, et al. Gavage of fecal samples from patients with colorectal cancer promotes intestinal carcinogenesis in germ-free and conventional mice. Gastroenterology. 2017;153(6):1621-1633.e6. https://doi.org/10.1053/j.gastro.2017.08.022.

    Article  PubMed  Google Scholar 

  54. Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillère R, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018;359(6371):91–7. https://doi.org/10.1126/science.aan3706.

    Article  CAS  PubMed  Google Scholar 

  55. Badgeley A, Anwar H, Modi K, Murphy P, Lakshmikuttyamma A. Effect of probiotics and gut microbiota on anti-cancer drugs: Mechanistic perspectives. Biochim Biophys Acta Rev Cancer. 2021;1875(1):188494. https://doi.org/10.1016/j.bbcan.2020.188494.

    Article  CAS  PubMed  Google Scholar 

  56. Davar D, Dzutsev AK, McCulloch JA, Rodrigues RR, Chauvin J-M, Morrison RM, et al. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients. Science. 2021;371(6529):595–602. https://doi.org/10.1126/science.abf3363.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Baruch EN, Youngster I, Ben-Betzalel G, Ortenberg R, Lahat A, Katz L, et al. Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. Science. 2021;371(6529):602–9. https://doi.org/10.1126/science.abb5920.

    Article  CAS  PubMed  Google Scholar 

  58. Ali H, Khurana S, Ma W, Peng Y, Jiang Z-D, DuPont H, et al. Safety and efficacy of fecal microbiota transplantation to treat and prevent recurrent Clostridioides difficile in cancer patients. J Cancer. 2021;12(21):6498–506. https://doi.org/10.7150/jca.59251.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Hefazi M, Patnaik MM, Hogan WJ, Litzow MR, Pardi DS, Khanna S. Safety and efficacy of fecal microbiota transplant for recurrent clostridium difficile infection in patients with cancer treated with cytotoxic chemotherapy: a single-institution retrospective case series. Mayo Clin Proc. 2017;92(11):1617–24. https://doi.org/10.1016/j.mayocp.2017.08.016.

    Article  CAS  PubMed  Google Scholar 

  60. Feuerstadt P, Louie TJ, Lashner B, Wang EEL, Diao L, Bryant JA, et al. SER-109, an oral microbiome therapy for recurrent clostridioides difficile infection. N Engl J Med. 2022;386(3):220–9. https://doi.org/10.1056/NEJMoa2106516.

    Article  CAS  PubMed  Google Scholar 

  61. Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al. Expert consensus document: the international scientific association for probiotics and prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11(8):506–14. https://doi.org/10.1038/nrgastro.2014.66.

    Article  PubMed  Google Scholar 

  62. Goderska K, Agudo Pena S, Alarcon T. Helicobacter pylori treatment: antibiotics or probiotics. Appl Microbiol Biotechnol. 2018;102(1):1–7. https://doi.org/10.1007/s00253-017-8535-7.

    Article  CAS  PubMed  Google Scholar 

  63. Dahiya D, Nigam PS. Biotherapy using probiotics as therapeutic agents to restore the gut microbiota to relieve gastrointestinal tract inflammation, IBD, IBS and prevent induction of cancer. Int J Mol Sci. 2023;24(6):5748. https://doi.org/10.3390/ijms24065748.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Ghanavati R, Akbari A, Mohammadi F, Asadollahi P, Javadi A, Talebi M, et al. Lactobacillus species inhibitory effect on colorectal cancer progression through modulating the Wnt/β-catenin signaling pathway. Mol Cell Biochem. 2020;470(1–2):1–13. https://doi.org/10.1007/s11010-020-03740-8.

    Article  CAS  PubMed  Google Scholar 

  65. Wang T, Zheng J, Dong S, Ismael M, Shan Y, Wang X, et al. Lacticaseibacillus rhamnosus LS8 ameliorates azoxymethane/dextran sulfate sodium-induced colitis-associated tumorigenesis in mice via regulating gut microbiota and inhibiting inflammation. Probiotics Antimicrob Proteins. 2022;14(5):947–59. https://doi.org/10.1007/s12602-022-09967-9.

    Article  CAS  PubMed  Google Scholar 

  66. Fahmy CA, Gamal-Eldeen AM, El-Hussieny EA, Raafat BM, Mehanna NS, Talaat RM, et al. Bifidobacterium longum suppresses murine colorectal cancer through the modulation of oncomiRs and tumor suppressor miRNAs. Nutr Cancer. 2019;71(4):688–700. https://doi.org/10.1080/01635581.2019.1577984.

    Article  CAS  PubMed  Google Scholar 

  67. Wan L, Wu C, Wu Q, Luo S, Liu J, Xie X. Impact of probiotics use on clinical outcomes of immunecheckpoint inhibitors therapy in cancer patients. Cancer Med. 2023;12(2):1841–9. https://doi.org/10.1002/cam4.4994.

    Article  CAS  PubMed  Google Scholar 

  68. Tomita Y, Goto Y, Sakata S, Imamura K, Minemura A, Oka K, et al. Clostridium butyricum therapy restores the decreased efficacy of immune checkpoint blockade in lung cancer patients receiving proton pump inhibitors. Oncoimmunology. 2022;11(1):2081010. https://doi.org/10.1080/2162402X.2022.2081010.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Ye Z, Liang L, Xu Y, Yang J, Li Y. Probiotics influence gut microbiota and tumor immune microenvironment to enhance anti-tumor efficacy of doxorubicin. Probiotics Antimicrob Proteins. 2023. https://doi.org/10.1007/s12602-023-10073-7.

    Article  PubMed  Google Scholar 

  70. Kim S, Kim Y, Lee S, Kim Y, Jeon B, Kim H, et al. Live biotherapeutic Lactococcus lactis GEN3013 enhances antitumor efficacy of cancer treatment via modulation of cancer progression and immune system. Cancers. 2022;14(17):4083. https://doi.org/10.3390/cancers14174083.

    Article  CAS  PubMed Central  Google Scholar 

  71. Wang F, Yin Q, Chen L, Davis MM. Bifidobacterium can mitigate intestinal immunopathology in the context of CTLA-4 blockade. Proc Natl Acad Sci USA. 2018;115(1):157–61. https://doi.org/10.1073/pnas.1712901115.

    Article  CAS  Google Scholar 

  72. Keen EC, Dantas G. Close encounters of three kinds: bacteriophages, commensal bacteria, and host immunity. Trends Microbiol. 2018;26(11):943–54. https://doi.org/10.1016/j.tim.2018.05.009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Koskella B, Brockhurst MA. Bacteria-phage coevolution as a driver of ecological and evolutionary processes in microbial communities. FEMS Microbiol Rev. 2014;38(5):916–31. https://doi.org/10.1111/1574-6976.12072.

    Article  CAS  PubMed  Google Scholar 

  74. Hsu BB, Gibson TE, Yeliseyev V, Liu Q, Lyon L, Bry L, et al. Dynamic modulation of the gut microbiota and metabolome by bacteriophages in a mouse model. Cell Host Microbe. 2019;25(6):803-814.e5. https://doi.org/10.1016/j.chom.2019.05.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Zheng D-W, Dong X, Pan P, Chen K-W, Fan J-X, Cheng S-X, et al. Phage-guided modulation of the gut microbiota of mouse models of colorectal cancer augments their responses to chemotherapy. Nat Biomed Eng. 2019;3(9):717–28. https://doi.org/10.1038/s41551-019-0423-2.

    Article  CAS  PubMed  Google Scholar 

  76. Oster P, Vaillant L, Riva E, McMillan B, Begka C, Truntzer C, et al. Helicobacter pylori infection has a detrimental impact on the efficacy of cancer immunotherapies. Gut. 2022;71(3):457–66. https://doi.org/10.1136/gutjnl-2020-323392.

    Article  CAS  Google Scholar 

  77. Islam MR, Arthur S, Haynes J, Butts MR, Nepal N, Sundaram U. The role of gut microbiota and metabolites in obesity-associated chronic gastrointestinal disorders. Nutrients. 2022;14(3):624. https://doi.org/10.3390/nu14030624.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Gentile CL, Weir TL. The gut microbiota at the intersection of diet and human health. Science. 2018;362(6416):776–80. https://doi.org/10.1126/science.aau5812.

    Article  CAS  PubMed  Google Scholar 

  79. Bradbury KE, Murphy N, Key TJ. Diet and colorectal cancer in UK Biobank: a prospective study. Int J Epidemiol. 2020;49(1):246–58. https://doi.org/10.1093/ije/dyz064.

    Article  PubMed  Google Scholar 

  80. Spencer CN, McQuade JL, Gopalakrishnan V, McCulloch JA, Vetizou M, Cogdill AP, et al. Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response. Science. 2021;374(6575):1632–40. https://doi.org/10.1126/science.aaz7015.

    Article  CAS  PubMed Central  Google Scholar 

  81. Song M, Chan AT. Environmental factors, gut microbiota, and colorectal cancer prevention. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2019;17(2):275–89. https://doi.org/10.1016/j.cgh.2018.07.012.

    Article  CAS  Google Scholar 

  82. Wirth M, Joachim J, Tooze SA. Autophagosome formation–the role of ULK1 and Beclin1-PI3KC3 complexes in setting the stage. Semin Cancer Biol. 2013;23(5):301–9. https://doi.org/10.1016/j.semcancer.2013.05.007.

    Article  CAS  PubMed  Google Scholar 

  83. Huang B, Gui M, Ni Z, He Y, Zhao J, Peng J, et al. Chemotherapeutic drugs induce different gut microbiota disorder pattern and NOD/RIP2/NF-κb signaling pathway activation that lead to different degrees of intestinal injury. Microbiol Spectr. 2022;10(6):e0167722. https://doi.org/10.1128/spectrum.01677-22.

    Article  CAS  PubMed  Google Scholar 

  84. Daillère R, Vétizou M, Waldschmitt N, Yamazaki T, Isnard C, Poirier-Colame V, et al. Enterococcus hirae and barnesiella intestinihominis facilitate cyclophosphamide-induced therapeutic immunomodulatory effects. Immunity. 2016;45(4):931–43. https://doi.org/10.1016/j.immuni.2016.09.009.

    Article  CAS  PubMed  Google Scholar 

  85. Picard M, Yonekura S, Slowicka K, Petta I, Rauber C, Routy B, et al. Ileal immune tonus is a prognosis marker of proximal colon cancer in mice and patients. Cell Death Differ. 2021;28(5):1532–47. https://doi.org/10.1038/s41418-020-00684-w.

    Article  CAS  Google Scholar 

  86. Roberti MP, Yonekura S, Duong CPM, Picard M, Ferrere G, Tidjani Alou M, et al. Chemotherapy-induced ileal crypt apoptosis and the ileal microbiome shape immunosurveillance and prognosis of proximal colon cancer. Nat Med. 2020;26(6):919–31. https://doi.org/10.1038/s41591-020-0882-8.

    Article  CAS  PubMed  Google Scholar 

  87. Yu T, Guo F, Yu Y, Sun T, Ma D, Han J, et al. Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy. Cell. 2017;170(3):548-563.e16. https://doi.org/10.1016/j.cell.2017.07.008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Xie Y-H, Gao Q-Y, Cai G-X, Sun X-M, Zou T-H, Chen H-M, et al. Fecal clostridium symbiosum for noninvasive detection of early and advanced colorectal cancer: test and validation studies. EBioMedicine. 2017;25:32–40. https://doi.org/10.1016/j.ebiom.2017.10.005.

    Article  CAS  PubMed Central  Google Scholar 

  89. Yuan L, Zhang S, Li H, Yang F, Mushtaq N, Ullah S, et al. The influence of gut microbiota dysbiosis to the efficacy of 5-Fluorouracil treatment on colorectal cancer. Biomed Pharmacother Biomedecine Pharmacother. 2018;108:184–93. https://doi.org/10.1016/j.biopha.2018.08.165.

    Article  CAS  Google Scholar 

  90. Tesniere A, Schlemmer F, Boige V, Kepp O, Martins I, Ghiringhelli F, et al. Immunogenic death of colon cancer cells treated with oxaliplatin. Oncogene. 2010;29(4):482–91. https://doi.org/10.1038/onc.2009.356.

    Article  CAS  PubMed  Google Scholar 

  91. Imai H, Saijo K, Komine K, Yoshida Y, Sasaki K, Suzuki A, et al. Antibiotics improve the treatment efficacy of oxaliplatin-based but not irinotecan-based therapy in advanced colorectal cancer patients. J Oncol. 2020;2020:1701326. https://doi.org/10.1155/2020/1701326.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Feather CE, Lees JG, Makker PGS, Goldstein D, Kwok JB, Moalem-Taylor G, et al. Oxaliplatin induces muscle loss and muscle-specific molecular changes in Mice. Muscle Nerve. 2018;57(4):650–8. https://doi.org/10.1002/mus.25966.

    Article  CAS  PubMed  Google Scholar 

  93. Wang J, Feng W, Zhang S, Chen L, Tang F, Sheng Y, et al. Gut microbial modulation in the treatment of chemotherapy-induced diarrhea with Shenzhu capsule. BMC Complement Altern Med. 2019;19(1):126. https://doi.org/10.1186/s12906-019-2548-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Wang Y, Sun L, Chen S, Guo S, Yue T, Hou Q, et al. The administration of Escherichia coli Nissle 1917 ameliorates irinotecan–induced intestinal barrier dysfunction and gut microbial dysbiosis in mice. Life Sci. 2019;231:116529. https://doi.org/10.1016/j.lfs.2019.06.004.

    Article  CAS  PubMed  Google Scholar 

  95. Yuan W, Xiao X, Yu X, Xie F, Feng P, Malik K, et al. Probiotic therapy (BIO-THREE) mitigates intestinal microbial imbalance and intestinal damage caused by oxaliplatin. Probiotics Antimicrob Proteins. 2022;14(1):60–71. https://doi.org/10.1007/s12602-021-09795-3.

    Article  CAS  PubMed  Google Scholar 

  96. Chang C-W, Lee H-C, Li L-H, Chiang Chiau J-S, Wang T-E, Chuang W-H, et al. Fecal microbiota transplantation prevents intestinal injury, upregulation of toll-like receptors, and 5-fluorouracil/oxaliplatin-induced toxicity in colorectal cancer. Int J Mol Sci. 2020;21(2):386. https://doi.org/10.3390/ijms21020386.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Zhu H, Lu C, Gao F, Qian Z, Yin Y, Kan S, et al. Selenium-enriched Bifidobacterium longum DD98 attenuates irinotecan-induced intestinal and hepatic toxicity in vitro and in vivo. Biomed Pharmacother. 2021;143:112192. https://doi.org/10.1016/j.biopha.2021.112192.

    Article  CAS  PubMed  Google Scholar 

  98. Mahdy MS, Azmy AF, Dishisha T, Mohamed WR, Ahmed KA, Hassan A, et al. Irinotecan-gut microbiota interactions and the capability of probiotics to mitigate Irinotecan-associated toxicity. BMC Microbiol. 2023;23(1):53. https://doi.org/10.1186/s12866-023-02791-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Mármol I, Quero J, Rodríguez-Yoldi MJ, Cerrada E. Gold as a possible alternative to platinum-based chemotherapy for colon cancer treatment. Cancers. 2019;11(6):780. https://doi.org/10.3390/cancers11060780.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Shen S, Lim G, You Z, Ding W, Huang P, Ran C, et al. Gut microbiota is critical for the induction of chemotherapy-induced pain. Nat Neurosci. 2017;20(9):1213–6. https://doi.org/10.1038/nn.4606.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. van der Hee B, Wells JM. Microbial regulation of host physiology by short-chain fatty acids. Trends Microbiol. 2021;29(8):700–12. https://doi.org/10.1016/j.tim.2021.02.001.

    Article  CAS  PubMed  Google Scholar 

  102. Poonacha KNT, Villa TG, Notario V. The interplay among radiation therapy, antibiotics and the microbiota: impact on cancer treatment outcomes. Antibiot Basel Switz. 2022;11(3):331. https://doi.org/10.3390/antibiotics11030331.

    Article  CAS  Google Scholar 

  103. Leibowitz BJ, Wei L, Zhang L, Ping X, Epperly M, Greenberger J, et al. Ionizing irradiation induces acute haematopoietic syndrome and gastrointestinal syndrome independently in mice. Nat Commun. 2014;5:3494. https://doi.org/10.1038/ncomms4494.

    Article  CAS  PubMed  Google Scholar 

  104. Zhao T-S, Xie L-W, Cai S, Xu J-Y, Zhou H, Tang L-F, et al. Dysbiosis of gut microbiota is associated with the progression of radiation-induced intestinal injury and is alleviated by oral compound probiotics in mouse model. Front Cell Infect Microbiol. 2021;11:717636. https://doi.org/10.3389/fcimb.2021.717636.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Reis Ferreira M, Andreyev HJN, Mohammed K, Truelove L, Gowan SM, Li J, et al. Microbiota and radiotherapy-induced gastrointestinal side-effects (MARS) study: a large pilot study of the microbiome in acute and late-radiation enteropathy. Clin Cancer Res. 2019;25(21):6487–500. https://doi.org/10.1158/1078-0432.CCR-19-0960.

    Article  PubMed  Google Scholar 

  106. Chen Z-Y, Xiao H-W, Dong J-L, Li Y, Wang B, Fan S-J, et al. Gut microbiota-derived PGF2α fights against radiation-induced lung toxicity through the MAPK/NF-κB pathway. Antioxidants. 2021;11(1):65. https://doi.org/10.3390/antiox11010065.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Ding X, Li Q, Li P, Chen X, Xiang L, Bi L, et al. Fecal microbiota transplantation: a promising treatment for radiation enteritis? Radiother Oncol. 2020;143:12–8. https://doi.org/10.1016/j.radonc.2020.01.011.

    Article  CAS  Google Scholar 

  108. Cui M, Xiao H, Li Y, Zhou L, Zhao S, Luo D, et al. Faecal microbiota transplantation protects against radiation-induced toxicity. EMBO Mol Med. 2017;9(4):448–61. https://doi.org/10.15252/emmm.201606932.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Xiao H, Fan Y, Li Y, Dong J, Zhang S, Wang B, et al. Oral microbiota transplantation fights against head and neck radiotherapy-induced oral mucositis in mice. Comput Struct Biotechnol J. 2021;19:5898–910. https://doi.org/10.1016/j.csbj.2021.10.028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Jian Y-P, Yang G, Zhang L-H, Liang J-Y, Zhou H-L, Wang Y-S, et al. Lactobacillus plantarum alleviates irradiation-induced intestinal injury by activation of FXR-FGF15 signaling in intestinal epithelia. J Cell Physiol. 2022;237(3):1845–56. https://doi.org/10.1002/jcp.30651.

    Article  CAS  PubMed  Google Scholar 

  111. Riehl TE, Alvarado D, Ee X, Zuckerman A, Foster L, Kapoor V, et al. Lactobacillus rhamnosus GG protects the intestinal epithelium from radiation injury through release of lipoteichoic acid, macrophage activation and the migration of mesenchymal stem cells. Gut. 2019;68(6):1003–13. https://doi.org/10.1136/gutjnl-2018-316226.

    Article  CAS  Google Scholar 

  112. Ting NL-N, Lau HC-H, Yu J. Cancer pharmacomicrobiomics: targeting microbiota to optimise cancer therapy outcomes. Gut. 2022;71(7):1412–25. https://doi.org/10.1136/gutjnl-2021-326264.

    Article  Google Scholar 

  113. Derosa L, Routy B, Thomas AM, Iebba V, Zalcman G, Friard S, et al. Intestinal akkermansia muciniphila predicts clinical response to Pd-1 blockade in patients with advanced non-small-cell lung cancer. Nat Med. 2022;28(2):315–24. https://doi.org/10.1038/s41591-021-01655-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, et al. Commensal bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015;350(6264):1084–9. https://doi.org/10.1126/science.aac4255.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Gao G, Shen S, Zhang T, Zhang J, Huang S, Sun Z, et al. Lacticaseibacillus rhamnosus probio-M9enhanced the antitumor response to anti-PD-1 therapy by modulating intestinal metabolites. EBioMedicine. 2023;91:104533. https://doi.org/10.1016/j.ebiom.2023.104533.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Vétizou M, Pitt JM, Daillère R, Lepage P, Waldschmitt N, Flament C, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015;350(6264):1079–84. https://doi.org/10.1126/science.aad1329.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Che H, Xiong Q, Ma J, Chen S, Wu H, Xu H, et al. Association of Helicobacter pylori infection with survival outcomes in advanced gastric cancer patients treated with immune checkpoint inhibitors. BMC Cancer. 2022;22(1):904. https://doi.org/10.1186/s12885-022-10004-9.

    Article  CAS  PubMed Central  Google Scholar 

  118. Pinato DJ, Howlett S, Ottaviani D, Urus H, Patel A, Mineo T, et al. Association of prior antibiotic treatment with survival and response to immune checkpoint inhibitor therapy in patients with cancer. JAMA Oncol. 2019;5(12):1774–8. https://doi.org/10.1001/jamaoncol.2019.2785.

    Article  PubMed Central  Google Scholar 

  119. Cheung KS, Lam LK, Seto WK, Leung WK. Use of Antibiotics during immune checkpoint inhibitor treatment is associated with lower survival in hepatocellular carcinoma. Liver Cancer. 2021;10(6):606–14. https://doi.org/10.1159/000518090.

    Article  CAS  PubMed Central  Google Scholar 

  120. Giordan Q, Salleron J, Vallance C, Moriana C, Clement-Duchene C. Impact of antibiotics and proton pump inhibitors on efficacy and tolerance of anti-PD-1 immune checkpoint inhibitors. Front Immunol. 2021;12:716317. https://doi.org/10.3389/fimmu.2021.716317.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Ochi N, Ichihara E, Takigawa N, Harada D, Inoue K, Shibayama T, et al. The effects of antibioticson the efficacy of immune checkpoint inhibitors in patients with non–small-cell lung cancer differ based on PD-L1 expression. Eur J Cancer. 2021;149:73–81. https://doi.org/10.1016/j.ejca.2021.02.040.

    Article  CAS  Google Scholar 

  122. Zitvogel L, Ma Y, Raoult D, Kroemer G, Gajewski TF. The microbiome in cancer immunotherapy: diagnostic tools and therapeutic strategies. Science. 2018;359(6382):1366–70. https://doi.org/10.1126/science.aar6918.

    Article  CAS  Google Scholar 

  123. Wang Y, Wiesnoski DH, Helmink BA, Gopalakrishnan V, Choi K, DuPont HL, et al. Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis. Nat Med. 2018;24(12):1804–8. https://doi.org/10.1038/s41591-018-0238-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, Gansu Province, China

    Yalan Chen, Xibin Wang, Yuwei Ye & Qian Ren

  2. Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu Province, China

    Yalan Chen, Xibin Wang, Yuwei Ye & Qian Ren

  3. Gansu Province Clinical Research Center for Digestive Diseases, Lanzhou University, Lanzhou, 730000, Gansu Province, China

    Yuwei Ye & Qian Ren

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Chen, Y., Wang, X., Ye, Y. et al. Gut microbiota in cancer: insights on microbial metabolites and therapeutic strategies. Med Oncol 41, 25 (2024). https://doi.org/10.1007/s12032-023-02249-6

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