Exploration of Targeted Anti-tumor Therapy

Table 1. Effects of probiotics, prebiotics, and synbiotics on gut health.

Intervention	Mechanism of action	Effect on gut microbiota	Impact on CRC prevention
Probiotics	Inactivate carcinogens and regulate apoptosis and cell differentiation. Helps restore the intestinal barrier and reduce inflammation	↑ Bifidobacterium, Akkermansia, Parabacteroides, Veillonella, Lactobacillus ↓ Porphyromonas, Fusobacterium, Alloprevotella, Prevotella	Improves gut environment, enhances barrier integrity, induces apoptosis in CRC cells, and reduces inflammation
Prebiotics	Selectively helps to stimulate beneficial bacteria, and ferments to produce SCFAs (esp. butyrate)	↑ Lactobacillus, Bifidobacterium, SCFA production (butyrate)	Maintains colonic epithelium integrity, reduces IL-6 and TNF-α, lowers mucosal damage, improves immune balance
Synbiotics	Synergistic effects: prebiotics nourish probiotics; ↑ SCFA (butyrate) production; regulate immune signaling	Enhanced balance of beneficial bacteria; ↑ SCFA synthesis	Decrease IL-6, STAT3, NF-κB, PGE-2, COX-2, TNF-α; reduce chronic inflammation and inhibit cancer-promoting pathways

Return to article view

The table summarizes the mechanisms and preventive effects of probiotics, prebiotics, along synbiotics in CRC. It is based on current evidence in this study. ↑: indicates an increase; ↓: indicates a decrease. CRC: colorectal cancer; SCFAs: short-chain fatty acids.

Declarations

Author contributions

TWK: Conceptualization, Writing—original draft, Writing—review & editing. LZ: Writing—review & editing. RS: Writing—review & editing. MUA: Writing—review & editing. CPB: Writing—review & editing. JMP: Writing—review & editing. MRW: Writing—review & editing. YF: Conceptualization, Supervision, Writing—review & editing. All authors read and approved the submitted version.

Conflicts of interest

Yujiang Fang, who is the Editorial Board Member of Exploration of Targeted Anti-tumor Therapy, had no involvement in the decision-making or the review process of this manuscript. The other authors declare no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

This study was supported by a grant from Des Moines University for Dr. Yujiang Fang [IOER 112-3119]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

References

Menon G, Recio-Boiles A, Lotfollahzadeh S, Cagir B. Colon Cancer. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2024. [PubMed]

Jiang Y, Yuan H, Li Z, Ji X, Shen Q, Tuo J, et al. Global pattern and trends of colorectal cancer survival: a systematic review of population-based registration data. Cancer Biol Med. 2021;19:175–86. [DOI] [PubMed] [PMC]

Mármol I, Sánchez-de-Diego C, Pradilla Dieste A, Cerrada E, Rodriguez Yoldi MJ. Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer. Int J Mol Sci. 2017;18:197. [DOI] [PubMed] [PMC]

Jin M, Shang F, Wu J, Fan Q, Chen C, Fan J, et al. Tumor-Associated Microbiota in Proximal and Distal Colorectal Cancer and Their Relationships With Clinical Outcomes. Front Microbiol. 2021;12:727937. [DOI] [PubMed] [PMC]

Milani C, Duranti S, Bottacini F, Casey E, Turroni F, Mahony J, et al. The First Microbial Colonizers of the Human Gut: Composition, Activities, and Health Implications of the Infant Gut Microbiota. Microbiol Mol Biol Rev. 2017;81:e00036–17. [DOI] [PubMed] [PMC]

Siddiqui R, Boghossian A, Alharbi AM, Alfahemi H, Khan NA. The Pivotal Role of the Gut Microbiome in Colorectal Cancer. Biology (Basel). 2022;11:1642. [DOI] [PubMed] [PMC]

Quaglio AEV, Grillo TG, De Oliveira ECS, Di Stasi LC, Sassaki LY. Gut microbiota, inflammatory bowel disease and colorectal cancer. World J Gastroenterol. 2022;28:4053–60. [DOI] [PubMed] [PMC]

He L, Zhong Z, Wen S, Li P, Jiang Q, Liu F. Gut microbiota-derived butyrate restores impaired regulatory T cells in patients with AChR myasthenia gravis via mTOR-mediated autophagy. Cell Commun Signal. 2024;22:215. [DOI] [PubMed] [PMC]

Caputi V, Giron MC. Microbiome-Gut-Brain Axis and Toll-Like Receptors in Parkinson’s Disease. Int J Mol Sci. 2018;19:1689. [DOI] [PubMed] [PMC]

10.

Song M, Chan AT, Sun J. Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer. Gastroenterology. 2020;158:322–40. [DOI] [PubMed] [PMC]

11.

Song M, Garrett WS, Chan AT. Nutrients, foods, and colorectal cancer prevention. Gastroenterology. 2015;148:1244–60. [DOI] [PubMed] [PMC]

12.

Brennan CA, Garrett WS. Fusobacterium nucleatum – symbiont, opportunist and oncobacterium. Nat Rev Microbiol. 2019;17:156–66. [DOI] [PubMed] [PMC]

13.

Nishida A, Inoue R, Inatomi O, Bamba S, Naito Y, Andoh A. Gut microbiota in the pathogenesis of inflammatory bowel disease. Clin J Gastroenterol. 2018;11:1–10. [DOI] [PubMed]

14.

Vyas U, Ranganathan N. Probiotics, prebiotics, and synbiotics: gut and beyond. Gastroenterol Res Pract. 2012;2012:872716. [DOI] [PubMed] [PMC]

15.

Cuevas-Ramos G, Petit CR, Marcq I, Boury M, Oswald E, Nougayrède J. Escherichia coli induces DNA damage in vivo and triggers genomic instability in mammalian cells. Proc Natl Acad Sci U S A. 2010;107:11537–42. [DOI] [PubMed] [PMC]

16.

Cheng Y, Ling Z, Li L. The Intestinal Microbiota and Colorectal Cancer. Front Immunol. 2020;11:615056. [DOI] [PubMed] [PMC]

17.

Grasso F, Frisan T. Bacterial Genotoxins: Merging the DNA Damage Response into Infection Biology. Biomolecules. 2015;5:1762–82. [DOI] [PubMed] [PMC]

18.

Avril M, DePaolo RW. “Driver-passenger” bacteria and their metabolites in the pathogenesis of colorectal cancer. Gut Microbes. 2021;13:1941710. [DOI] [PubMed] [PMC]

19.

Cao Y, Oh J, Xue M, Huh WJ, Wang J, Gonzalez-Hernandez JA, et al. Commensal microbiota from patients with inflammatory bowel disease produce genotoxic metabolites. Science. 2022;378:eabm3233. [DOI] [PubMed] [PMC]

20.

Kostic AD, Chun E, Robertson L, Glickman JN, Gallini CA, Michaud M, et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe. 2013;14:207–15. [DOI] [PubMed] [PMC]

21.

Shenker BJ, Datar S. Fusobacterium nucleatum inhibits human T-cell activation by arresting cells in the mid-G1 phase of the cell cycle. Infect Immun. 1995;63:4830–6. [DOI] [PubMed] [PMC]

22.

Goto N, Westcott PMK, Goto S, Imada S, Taylor MS, Eng G, et al. SOX17 enables immune evasion of early colorectal adenomas and cancers. Nature. 2024;627:636–45. [DOI] [PubMed] [PMC]

23.

Gao J, Shi LZ, Zhao H, Chen J, Xiong L, He Q, et al. Loss of IFN-γ Pathway Genes in Tumor Cells as a Mechanism of Resistance to Anti-CTLA-4 Therapy. Cell. 2016;167:397–404. [DOI] [PubMed] [PMC]

24.

Chen J, Pitmon E, Wang K. Microbiome, inflammation and colorectal cancer. Semin Immunol. 2017;32:43–53. [DOI] [PubMed]

25.

Fang Y, Yan C, Zhao Q, Xu J, Liu Z, Gao J, et al. The roles of microbial products in the development of colorectal cancer: a review. Bioengineered. 2021;12:720–35. [DOI] [PubMed] [PMC]

26.

Chung L, Thiele Orberg E, Geis AL, Chan JL, Fu K, DeStefano Shields CE, et al. Bacteroides fragilis Toxin Coordinates a Pro-carcinogenic Inflammatory Cascade via Targeting of Colonic Epithelial Cells. Cell Host Microbe. 2018;23:203–14. [DOI] [PubMed] [PMC]

27.

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. [DOI] [PubMed]

28.

Liu Y, Zhang S, Zhou W, Hu D, Xu H, Ji G. Secondary Bile Acids and Tumorigenesis in Colorectal Cancer. Front Oncol. 2022;12:813745. [DOI] [PubMed] [PMC]

29.

Kaźmierczak-Siedlecka K, Marano L, Merola E, Roviello F, Połom K. Sodium butyrate in both prevention and supportive treatment of colorectal cancer. Front Cell Infect Microbiol. 2022;12:1023806. [DOI] [PubMed] [PMC]

30.

Gao Z, Yin J, Zhang J, Ward RE, Martin RJ, Lefevre M, et al. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes. 2009;58:1509–17. [DOI] [PubMed] [PMC]

31.

Pelgrim CE, Franx BAA, Snabel J, Kleemann R, Arnoldussen IAC, Kiliaan AJ. Butyrate Reduces HFD-Induced Adipocyte Hypertrophy and Metabolic Risk Factors in Obese LDLr-/-.Leiden Mice. Nutrients. 2017;9:714. [DOI] [PubMed] [PMC]

32.

Chen G, Ran X, Li B, Li Y, He D, Huang B, et al. Sodium Butyrate Inhibits Inflammation and Maintains Epithelium Barrier Integrity in a TNBS-induced Inflammatory Bowel Disease Mice Model. EBioMedicine. 2018;30:317–25. [DOI] [PubMed] [PMC]

33.

Blaak EE, Canfora EE, Theis S, Frost G, Groen AK, Mithieux G, et al. Short chain fatty acids in human gut and metabolic health. Benef Microbes. 2020;11:411–55. [DOI] [PubMed]

34.

He J, Zhang P, Shen L, Niu L, Tan Y, Chen L, et al. Short-Chain Fatty Acids and Their Association with Signalling Pathways in Inflammation, Glucose and Lipid Metabolism. Int J Mol Sci. 2020;21:6356. [DOI] [PubMed] [PMC]

35.

Hosseini E, Grootaert C, Verstraete W, Van de Wiele T. Propionate as a health-promoting microbial metabolite in the human gut. Nutr Rev. 2011;69:245–58. [DOI] [PubMed]

36.

Kvakova M, Kamlarova A, Stofilova J, Benetinova V, Bertkova I. Probiotics and postbiotics in colorectal cancer: Prevention and complementary therapy. World J Gastroenterol. 2022;28:3370–82. [DOI] [PubMed] [PMC]

37.

Park IJ, Lee JH, Kye BH, Oh HK, Cho YB, Kim YT, et al. Effects of PrObiotics on the Symptoms and Surgical ouTComes after Anterior REsection of Colon Cancer (POSTCARE): A Randomized, Double-Blind, Placebo-Controlled Trial. J Clin Med. 2020;9:2181. [DOI] [PubMed] [PMC]

38.

Fong W, Li Q, Yu J. Gut microbiota modulation: a novel strategy for prevention and treatment of colorectal cancer. Oncogene. 2020;39:4925–43. [DOI] [PubMed] [PMC]

39.

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;234:17127–43. [DOI] [PubMed]

40.

Klaenhammer TR, Kleerebezem M, Kopp MV, Rescigno M. The impact of probiotics and prebiotics on the immune system. Nat Rev Immunol. 2012;12:728–34. [DOI] [PubMed]

41.

Gibson GR, Hutkins R, Sanders ME, Prescott SL, Reimer RA, Salminen SJ, et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017;14:491–502. [DOI] [PubMed]

42.

Holscher HD. Dietary fiber and prebiotics and the gastrointestinal microbiota. Gut Microbes. 2017;8:172–84. [DOI] [PubMed] [PMC]

43.

Davani-Davari D, Negahdaripour M, Karimzadeh I, Seifan M, Mohkam M, Masoumi SJ, et al. Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications. Foods. 2019;8:92. [DOI] [PubMed] [PMC]

44.

Ren Y, Nie L, Luo C, Zhu S, Zhang X. Advancement in Therapeutic Intervention of Prebiotic-Based Nanoparticles for Colonic Diseases. Int J Nanomedicine. 2022;17:6639–54. [DOI] [PubMed] [PMC]

45.

Sorrenti V, Ali S, Mancin L, Davinelli S, Paoli A, Scapagnini G. Cocoa Polyphenols and Gut Microbiota Interplay: Bioavailability, Prebiotic Effect, and Impact on Human Health. Nutrients. 2020;12:1908. [DOI] [PubMed] [PMC]

46.

Parada Venegas D, De la Fuente MK, Landskron G, González MJ, Quera R, Dijkstra G, et al. Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases. Front Immunol. 2019;10:277. [DOI] [PubMed] [PMC]

47.

Alli SR, Gorbovskaya I, Liu JCW, Kolla NJ, Brown L, Müller DJ. The Gut Microbiome in Depression and Potential Benefit of Prebiotics, Probiotics and Synbiotics: A Systematic Review of Clinical Trials and Observational Studies. Int J Mol Sci. 2022;23:4494. [DOI] [PubMed] [PMC]

48.

Chen J, Vitetta L. Gut Microbiota Metabolites in NAFLD Pathogenesis and Therapeutic Implications. Int J Mol Sci. 2020;21:5214. [DOI] [PubMed] [PMC]

49.

Hirano T. IL-6 in inflammation, autoimmunity and cancer. Int Immunol. 2021;33:127–48. [DOI] [PubMed] [PMC]

50.

Saito Y, Hinoi T, Adachi T, Miguchi M, Niitsu H, Kochi M, et al. Synbiotics suppress colitis-induced tumorigenesis in a colon-specific cancer mouse model. PLoS One. 2019;14:e0216393. [DOI] [PubMed] [PMC]

51.

Wang JW, Kuo CH, Kuo FC, Wang YK, Hsu WH, Yu FJ, et al. Fecal microbiota transplantation: Review and update. J Formos Med Assoc. 2019;118:S23–31. [DOI] [PubMed]

52.

Gulati M, Singh SK, Corrie L, Kaur IP, Chandwani L. Delivery routes for faecal microbiota transplants: Available, anticipated and aspired. Pharmacol Res. 2020;159:104954. [DOI] [PubMed]

53.

Huang J, Zheng X, Kang W, Hao H, Mao Y, Zhang H, et al. Metagenomic and metabolomic analyses reveal synergistic effects of fecal microbiota transplantation and anti-PD-1 therapy on treating colorectal cancer. Front Immunol. 2022;13:874922. [DOI] [PubMed] [PMC]

54.

Durant L, Stentz R, Noble A, Brooks J, Gicheva N, Reddi D, et al. Bacteroides thetaiotaomicron-derived outer membrane vesicles promote regulatory dendritic cell responses in health but not in inflammatory bowel disease. Microbiome. 2020;8:88. [DOI] [PubMed] [PMC]

55.

Ryu TY, Kim K, Han TS, Lee MO, Lee J, Choi J, et al. Human gut-microbiome-derived propionate coordinates proteasomal degradation via HECTD2 upregulation to target EHMT2 in colorectal cancer. ISME J. 2022;16:1205–21. [DOI] [PubMed] [PMC]