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Clin Colon Rectal Surg 2023; 36(02): 112-119
DOI: 10.1055/s-0043-1760864
Review Article

The Influence of the Microbiome on Metastatic Colorectal Cancer

Samuel Cass
1   Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
,
Michael G. White
2   Department of Colon & Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas
› Author Affiliations Funding SC is supported by the National Institutes of Health (T32 CA 009599) and the MD Anderson Cancer Center support grant (P30 CA016672).
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Abstract

The microbiome (bacteria, viruses, and fungi) that exist within a patient's gastrointestinal tract and throughout their body have been increasingly understood to play a critical role in a variety of disease, including a number of cancer histologies. These microbial colonies are reflective of a patient's overall health state, their exposome, and germline genetics. In the case of colorectal adenocarcinoma, significant progress has been made in understanding the mechanism the microbiome plays beyond mere associations in both disease initiation and progression. Importantly, this improved understanding holds the potential to further identify the role these microbes play in colorectal cancer. We hope this improved understanding will be able to be leveraged in the future through either biomarkers or next-generation therapeutics to augment contemporary treatment algorithms through the manipulation of a patient's microbiome—whether through diet, antibiotics, prebiotics, or novel therapeutics. Here we review the role of the microbiome in the setting of patients with stage IV colorectal adenocarcinoma in both the development and progression or disease as well as response to therapeutics.

Keywords

colorectal adenocarcinoma - colorectal liver metastasis - colorectal carcinomatosis - gut microbiome


Publication History

Article published online:
25 January 2023

© 2023. Thieme. All rights reserved.

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  • References

  • 1 American Cancer Society. Cancer Facts & Figures 2020. Atlanta, GA: American Cancer Society; 2020
    Search in Google Scholar
  • 2 Yu J, Feng Q, Wong SH. et al. Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer. Gut 2017; 66 (01) 70-78
    CrossrefPubMedSearch in Google Scholar
  • 3 Yachida S, Mizutani S, Shiroma H. et al. Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer. Nat Med 2019; 25 (06) 968-976
    CrossrefPubMedSearch in Google Scholar
  • 4 Nakatsu G, Li X, Zhou H. et al. Gut mucosal microbiome across stages of colorectal carcinogenesis. Nat Commun 2015; 6: 8727
    CrossrefPubMedSearch in Google Scholar
  • 5 Mima K, Nishihara R, Qian ZR. et al. Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis. Gut 2016; 65 (12) 1973-1980
    CrossrefPubMedSearch in Google Scholar
  • 6 Emlet C, Ruffin M, Lamendella R. Enteric virome and carcinogenesis in the gut. Dig Dis Sci 2020; 65 (03) 852-864
    CrossrefPubMedSearch in Google Scholar
  • 7 Poore GD, Kopylova E, Zhu Q. et al. Microbiome analyses of blood and tissues suggest cancer diagnostic approach. Nature 2020; 579 (7800): 567-574
    CrossrefPubMedSearch in Google Scholar
  • 8 Flanagan L, Schmid J, Ebert M. et al. Fusobacterium nucleatum associates with stages of colorectal neoplasia development, colorectal cancer and disease outcome. Eur J Clin Microbiol Infect Dis 2014; 33 (08) 1381-1390
    CrossrefPubMedSearch in Google Scholar
  • 9 Yu T, Guo F, Yu Y. et al. Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy. Cell 2017; 170 (03) 548-563.e16
    CrossrefPubMedSearch in Google Scholar
  • 10 Serna G, Ruiz-Pace F, Hernando J. et al. Fusobacterium nucleatum persistence and risk of recurrence after preoperative treatment in locally advanced rectal cancer. Ann Oncol 2020; 31 (10) 1366-1375
    CrossrefPubMedSearch in Google Scholar
  • 11 Dejea CM, Fathi P, Craig JM. et al. Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria. Science 2018; 359 (6375): 592-597
    CrossrefPubMedSearch in Google Scholar
  • 12 Wu S, Rhee KJ, Albesiano E. et al. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med 2009; 15 (09) 1016-1022
    CrossrefPubMedSearch in Google Scholar
  • 13 DeStefano Shields CE, White JR, Chung L. et al. Bacterial-driven inflammation and mutant BRAF expression combine to promote murine colon tumorigenesis that is sensitive to immune checkpoint therapy. Cancer Discov 2021; 11 (07) 1792-1807
    CrossrefPubMedSearch in Google Scholar
  • 14 Yu SY, Xie YH, Qiu YW, Chen YX, Fang JY. Moderate alteration to gut microbiota brought by colorectal adenoma resection. J Gastroenterol Hepatol 2019; 34 (10) 1758-1765
    CrossrefPubMedSearch in Google Scholar
  • 15 Goto S, Hasegawa S, Hida K. et al; Study Group for Nomogram of the Japanese Society for Cancer of the Colon and Rectum. Multicenter analysis of impact of anastomotic leakage on long-term oncologic outcomes after curative resection of colon cancer. Surgery 2017; 162 (02) 317-324
    CrossrefPubMedSearch in Google Scholar
  • 16 Gaines S, Shao C, Hyman N, Alverdy JC. Gut microbiome influences on anastomotic leak and recurrence rates following colorectal cancer surgery. Br J Surg 2018; 105 (02) e131-e141
    CrossrefPubMedSearch in Google Scholar
  • 17 Olivas AD, Shogan BD, Valuckaite V. et al. Intestinal tissues induce an SNP mutation in Pseudomonas aeruginosa that enhances its virulence: possible role in anastomotic leak. PLoS One 2012; 7 (08) e44326
    CrossrefPubMedSearch in Google Scholar
  • 18 Shogan BD, Belogortseva N, Luong PM. et al. Collagen degradation and MMP9 activation by Enterococcus faecalis contribute to intestinal anastomotic leak. Sci Transl Med 2015; 7 (286) 286ra68
    CrossrefPubMedSearch in Google Scholar
  • 19 Zhang LM, Schuitevoerder D, White MG. et al. combined mechanical and oral antibiotic bowel preparation is associated with prolonged recurrence-free survival following surgery for colorectal cancer. J Surg Oncol 2021; 124 (07) 1106-1114
    CrossrefPubMedSearch in Google Scholar
  • 20 Gaines S, van Praagh JB, Williamson AJ. et al. Western diet promotes intestinal colonization by collagenolytic microbes and promotes tumor formation after colorectal surgery. Gastroenterology 2020; 158 (04) 958-970.e2
    CrossrefPubMedSearch in Google Scholar
  • 21 Lin D, Peters BA, Friedlander C. et al. Association of dietary fibre intake and gut microbiota in adults. Br J Nutr 2018; 120 (09) 1014-1022
    CrossrefPubMedSearch in Google Scholar
  • 22 Zhou E, Rifkin S. Colorectal cancer and diet: risk versus prevention, is diet an intervention?. Gastroenterol Clin North Am 2021; 50 (01) 101-111
    CrossrefPubMedSearch in Google Scholar
  • 23 Meyerhardt JA, Niedzwiecki D, Hollis D. et al. Association of dietary patterns with cancer recurrence and survival in patients with stage III colon cancer. JAMA 2007; 298 (07) 754-764
    CrossrefPubMedSearch in Google Scholar
  • 24 Vigneswaran J, Shogan BD. The role of the intestinal microbiome on colorectal cancer pathogenesis and its recurrence following surgery. J Gastrointest Surg 2020; 24 (10) 2349-2356
    CrossrefPubMedSearch in Google Scholar
  • 25 Kaplan RN, Riba RD, Zacharoulis S. et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 2005; 438 (7069) 820-827
    CrossrefPubMedSearch in Google Scholar
  • 26 Peinado H, Zhang H, Matei IR. et al. Pre-metastatic niches: organ-specific homes for metastases. Nat Rev Cancer 2017; 17 (05) 302-317
    CrossrefPubMedSearch in Google Scholar
  • 27 Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med 2013; 19 (11) 1423-1437
    CrossrefPubMedSearch in Google Scholar
  • 28 Joyce JA, Pollard JW. Microenvironmental regulation of metastasis. Nat Rev Cancer 2009; 9 (04) 239-252
    CrossrefPubMedSearch in Google Scholar
  • 29 Psaila B, Lyden D. The metastatic niche: adapting the foreign soil. Nat Rev Cancer 2009; 9 (04) 285-293
    CrossrefPubMedSearch in Google Scholar
  • 30 Ordóñez-Morán P, Huelsken J. Complex metastatic niches: already a target for therapy?. Curr Opin Cell Biol 2014; 31: 29-38
    CrossrefPubMedSearch in Google Scholar
  • 31 Spadoni I, Zagato E, Bertocchi A. et al. A gut-vascular barrier controls the systemic dissemination of bacteria. Science 2015; 350 (6262): 830-834
    CrossrefPubMedSearch in Google Scholar
  • 32 Spadoni I, Pietrelli A, Pesole G, Rescigno M. Gene expression profile of endothelial cells during perturbation of the gut vascular barrier. Gut Microbes 2016; 7 (06) 540-548
    CrossrefPubMedSearch in Google Scholar
  • 33 Cheng C, Tan J, Qian W, Zhang L, Hou X. Gut inflammation exacerbates hepatic injury in the high-fat diet induced NAFLD mouse: attention to the gut-vascular barrier dysfunction. Life Sci 2018; 209: 157-166
    CrossrefPubMedSearch in Google Scholar
  • 34 Bertocchi A, Carloni S, Ravenda PS. et al. Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver. Cancer Cell 2021; 39 (05) 708-724.e11
    CrossrefPubMedSearch in Google Scholar
  • 35 Mouries J, Brescia P, Silvestri A. et al. Microbiota-driven gut vascular barrier disruption is a prerequisite for non-alcoholic steatohepatitis development. J Hepatol 2019; 71 (06) 1216-1228
    CrossrefPubMedSearch in Google Scholar
  • 36 Meena AS, Shukla PK, Sheth P, Rao R. EGF receptor plays a role in the mechanism of glutamine-mediated prevention of alcohol-induced gut barrier dysfunction and liver injury. J Nutr Biochem 2019; 64: 128-143
    CrossrefPubMedSearch in Google Scholar
  • 37 Bullman S, Pedamallu CS, Sicinska E. et al. Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Science 2017; 358 (6369): 1443-1448
    CrossrefPubMedSearch in Google Scholar
  • 38 Yu J, Chen Y, Fu X. et al. Invasive Fusobacterium nucleatum may play a role in the carcinogenesis of proximal colon cancer through the serrated neoplasia pathway. Int J Cancer 2016; 139 (06) 1318-1326
    CrossrefPubMedSearch in Google Scholar
  • 39 Engstrand J, Nilsson H, Strömberg C, Jonas E, Freedman J. Colorectal cancer liver metastases - a population-based study on incidence, management and survival. BMC Cancer 2018; 18 (01) 78
    CrossrefPubMedSearch in Google Scholar
  • 40 Yu LX, Schwabe RF. The gut microbiome and liver cancer: mechanisms and clinical translation. Nat Rev Gastroenterol Hepatol 2017; 14 (09) 527-539
    CrossrefPubMedSearch in Google Scholar
  • 41 Tripathi A, Debelius J, Brenner DA. et al. The gut-liver axis and the intersection with the microbiome. Nat Rev Gastroenterol Hepatol 2018; 15 (07) 397-411
    CrossrefPubMedSearch in Google Scholar
  • 42 Loo TM, Kamachi F, Watanabe Y. et al. Gut microbiota promotes obesity-associated liver cancer through PGE2-mediated suppression of antitumor immunity. Cancer Discov 2017; 7 (05) 522-538
    CrossrefPubMedSearch in Google Scholar
  • 43 Sipe LM, Chaib M, Pingili AK, Pierre JF, Makowski L. Microbiome, bile acids, and obesity: how microbially modified metabolites shape anti-tumor immunity. Immunol Rev 2020; 295 (01) 220-239
    CrossrefPubMedSearch in Google Scholar
  • 44 Clarke TB, Davis KM, Lysenko ES, Zhou AY, Yu Y, Weiser JN. Recognition of peptidoglycan from the microbiota by Nod1 enhances systemic innate immunity. Nat Med 2010; 16 (02) 228-231
    CrossrefPubMedSearch in Google Scholar
  • 45 Sakamoto Y, Mima K, Ishimoto T. et al. Relationship between Fusobacterium nucleatum and antitumor immunity in colorectal cancer liver metastasis. Cancer Sci 2021; 112 (11) 4470-4477
    CrossrefPubMedSearch in Google Scholar
  • 46 Kostic AD, Chun E, Robertson L. et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe 2013; 14 (02) 207-215
    CrossrefPubMedSearch in Google Scholar
  • 47 Chen Y, Liu Z, Liang S. et al. Role of Kupffer cells in the induction of tolerance of orthotopic liver transplantation in rats. Liver Transpl 2008; 14 (06) 823-836
    CrossrefPubMedSearch in Google Scholar
  • 48 Gong J, Cao D, Chen Y, Li J, Gong J, Zeng Z. Role of programmed death ligand 1 and Kupffer cell in immune regulation after orthotopic liver transplantation in rats. Int Immunopharmacol 2017; 48: 8-16
    CrossrefPubMedSearch in Google Scholar
  • 49 Li R, Zhou R, Wang H. et al. Gut microbiota-stimulated cathepsin K secretion mediates TLR4-dependent M2 macrophage polarization and promotes tumor metastasis in colorectal cancer. Cell Death Differ 2019; 26 (11) 2447-2463
    CrossrefPubMedSearch in Google Scholar
  • 50 Miao R, Badger TC, Groesch K. et al. Assessment of peritoneal microbial features and tumor marker levels as potential diagnostic tools for ovarian cancer. PLoS One 2020; 15 (01) e0227707
    CrossrefPubMedSearch in Google Scholar
  • 51 Sipos A, Ujlaki G, Mikó E. et al. The role of the microbiome in ovarian cancer: mechanistic insights into oncobiosis and to bacterial metabolite signaling. Mol Med 2021; 27 (01) 33
    CrossrefPubMedSearch in Google Scholar
  • 52 Carr NJ. New insights in the pathology of peritoneal surface malignancy. J Gastrointest Oncol 2021; 12 (Suppl. 01) S216-S229
    CrossrefPubMedSearch in Google Scholar
  • 53 Gilbreath JJ, Semino-Mora C, Friedline CJ. et al. A core microbiome associated with the peritoneal tumors of pseudomyxoma peritonei. Orphanet J Rare Dis 2013; 8: 105
    CrossrefPubMedSearch in Google Scholar
  • 54 Semino-Mora C, Liu H, McAvoy T. et al. Pseudomyxoma peritonei: is disease progression related to microbial agents? A study of bacteria, MUC2 AND MUC5AC expression in disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis. Ann Surg Oncol 2008; 15 (05) 1414-1423
    CrossrefPubMedSearch in Google Scholar
  • 55 Semino-Mora C, Testerman TL, Liu H. et al. Antibiotic treatment decreases microbial burden associated with pseudomyxoma peritonei and affects β-catenin distribution. Clin Cancer Res 2013; 19 (14) 3966-3976
    CrossrefPubMedSearch in Google Scholar
  • 56 Montassier E, Gastinne T, Vangay P. et al. Chemotherapy-driven dysbiosis in the intestinal microbiome. Aliment Pharmacol Ther 2015; 42 (05) 515-528
    CrossrefPubMedSearch in Google Scholar
  • 57 Wertman JN, Dunn KA, Kulkarni K. The impact of the host intestinal microbiome on carcinogenesis and the response to chemotherapy. Future Oncol 2021; 17 (32) 4371-4387
    CrossrefPubMedSearch in Google Scholar
  • 58 Villéger R, Lopès A, Carrier G. et al. Intestinal microbiota: a novel target to improve anti-tumor treatment?. Int J Mol Sci 2019; 20 (18) 4584
    CrossrefPubMedSearch in Google Scholar
  • 59 Viaud S, Saccheri F, Mignot G. et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science 2013; 342 (6161): 971-976
    CrossrefPubMedSearch in Google Scholar
  • 60 Daillère R, Vétizou M, Waldschmitt N. et al. Enterococcus hirae and Barnesiella intestinihominis facilitate cyclophosphamide-induced therapeutic immunomodulatory effects. Immunity 2016; 45 (04) 931-943
    CrossrefPubMedSearch in Google Scholar
  • 61 Iida N, Dzutsev A, Stewart CA. et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science 2013; 342 (6161): 967-970
    CrossrefPubMedSearch in Google Scholar
  • 62 Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin 2022; 72 (01) 7-33
    Search in Google Scholar
  • 63 Andrews MC, Duong CPM, Gopalakrishnan V. et al. Gut microbiota signatures are associated with toxicity to combined CTLA-4 and PD-1 blockade. Nat Med 2021; 27 (08) 1432-1441
    CrossrefPubMedSearch in Google Scholar
  • 64 Gopalakrishnan V, Spencer CN, Nezi L. et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 2018; 359 (6371): 97-103
    CrossrefPubMedSearch in Google Scholar
  • 65 Routy B, Le Chatelier E, Derosa L. et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 2018; 359 (6371): 91-97
    CrossrefPubMedSearch in Google Scholar
  • 66 Matson V, Fessler J, Bao R. et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science 2018; 359 (6371): 104-108
    CrossrefPubMedSearch in Google Scholar
  • 67. Overman MJ, Lonardi S, Wong KYM. et al. Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer. J Clin Oncol 2018; 36 (08) 773-779
    CrossrefPubMedSearch in Google Scholar
  • 68 Kawakami H, Zaanan A, Sinicrope FA. Microsatellite instability testing and its role in the management of colorectal cancer. Curr Treat Options Oncol 2015; 16 (07) 30
    CrossrefPubMedSearch in Google Scholar
  • 69 Giannakis M, Mu XJ, Shukla SA. et al. Genomic correlates of immune-cell infiltrates in colorectal carcinoma. Cell Rep 2016; 15 (04) 857-865
    CrossrefPubMedSearch in Google Scholar
  • 70 Sahin IH, Ciombor KK, Diaz LA, Yu J, Kim R. Immunotherapy for microsatellite stable colorectal cancers: challenges and novel therapeutic avenues. Am Soc Clin Oncol Educ Book 2022; 42: 1-12
    PubMedSearch in Google Scholar
  • 71 Wang F, He MM, Yao YC. et al. Regorafenib plus toripalimab in patients with metastatic colorectal cancer: a phase Ib/II clinical trial and gut microbiome analysis. Cell Rep Med 2021; 2 (09) 100383
    CrossrefPubMedSearch in Google Scholar
  • 72 Ferreira MR, Muls A, Dearnaley DP, Andreyev HJ. Microbiota and radiation-induced bowel toxicity: lessons from inflammatory bowel disease for the radiation oncologist. Lancet Oncol 2014; 15 (03) e139-e147
    CrossrefPubMedSearch in Google Scholar
  • 73 Yi Y, Shen L, Shi W. et al. Gut microbiome components predict response to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer: a prospective, longitudinal study. Clin Cancer Res 2021; 27 (05) 1329-1340
    CrossrefPubMedSearch in Google Scholar
  • 74 Crawford PA, Gordon JI. Microbial regulation of intestinal radiosensitivity. Proc Natl Acad Sci U S A 2005; 102 (37) 13254-13259
    CrossrefPubMedSearch in Google Scholar
  • 75 Cui M, Xiao H, Li Y. et al. Faecal microbiota transplantation protects against radiation-induced toxicity. EMBO Mol Med 2017; 9 (04) 448-461
    CrossrefPubMedSearch in Google Scholar