Can the microbiota predict response to systemic cancer therapy, surgical outcomes, and survival? The answer is in the gut

References

• El Bairi K, Amrani M, Kandhro AH, et al. Prediction of therapy response in ovarian cancer: where are we now? Crit Rev Clin Lab Sci. 2017;54(4):233–266.
   PubMed Web of Science ®Google Scholar
• Kelloff GJ, Sigman CC. Cancer biomarkers: selecting the right drug for the right patient. Nat Rev Drug Discov. 2012;11(3):201–214.
   PubMed Web of Science ®Google Scholar
• El Bairi K, Amrani M, Afqir S, Starvation tactics using natural compounds for advanced cancers: pharmacodynamics, clinical efficacy, and predictive biomarkers. Cancer Med. 2018;7(6):2221–2246.
   PubMed Web of Science ®Google Scholar
• Saner FAM, Herschtal A, Nelson BH, et al. Going to extremes: determinants of extraordinary response and survival in patients with cancer. Nat Rev Cancer. 2019. DOI:10.1038/s41568-019-0145-5
   PubMed Web of Science ®Google Scholar
• Alexander JL, Wilson ID, Teare J, et al. Gut microbiota modulation of chemotherapy efficacy and toxicity. Nat Rev Gastroenterol Hepatol. 2017;14(6):356–365.
   PubMed Web of Science ®Google Scholar
• Panebianco C, Andriulli A, Pazienza V. Pharmacomicrobiomics: exploiting the drug-microbiota interactions in anticancer therapies. Microbiome. 2018;6(1):92.
   PubMedGoogle Scholar
• Fessler J, Matson V, Gajewski TF. Exploring the emerging role of the microbiome in cancer immunotherapy. J Immunother Cancer. 2019;7(1):108.
   PubMed Web of Science ®Google Scholar
• Gopalakrishnan V, Helmink BA, Spencer CN, et al. The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy. Cancer Cell. 2018;33(4):570–580.
   PubMed Web of Science ®Google Scholar
• Liu T, Xiong Q, Li L, et al. Intestinal microbiota predicts lung cancer patients at risk of immune-related diarrhea. Immunotherapy. 2019;11(5):385–396.
   PubMed Web of Science ®Google Scholar
• Secombe KR, Coller JK, Gibson RJ, et al. The bidirectional interaction of the gut microbiome and the innate immune system: implications for chemotherapy-induced gastrointestinal toxicity. Int J Cancer. 2019;144(10):2365–2376.
   PubMed Web of Science ®Google Scholar
• Dubin K, Callahan MK, Ren B, et al. Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis. Nat Commun. 2016;7:10391.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Zhang S, Yang Y, Weng W, et al. Fusobacterium nucleatum promotes chemoresistance to 5-fluorouracil by upregulation of BIRC3 expression in colorectal cancer. J Exp Clin Cancer Res. 2019;38(1):14.
   PubMedGoogle Scholar
• Oh HJ, Kim JH, Bae JM, et al. Prognostic impact of fusobacterium nucleatum depends on combined tumor location and microsatellite instability status in Stage II/III colorectal cancers treated with adjuvant chemotherapy. J Pathol Transl Med. 2019;53(1):40–49.
   PubMed Web of Science ®Google Scholar
• Lee DW, Han SW, Kang JK, et al. Association between fusobacterium nucleatum, pathway mutation, and patient prognosis in colorectal cancer. Ann Surg Oncol. 2018;25(11):3389–3395.
   PubMed Web of Science ®Google Scholar
• Yamaoka Y, Suehiro Y, Hashimoto S, et al. Fusobacterium nucleatum as a prognostic marker of colorectal cancer in a Japanese population. J Gastroenterol. 2018;53(4):517–524.
   PubMed Web of Science ®Google Scholar
• Yuan L, Zhang S, Li H, et al. The influence of gut microbiota dysbiosis to the efficacy of 5-Fluorouracil treatment on colorectal cancer. Biomed Pharmacother. 2018;108:184–193.
   PubMed Web of Science ®Google Scholar
• Deng X, Li Z, Li G, et al. Comparison of microbiota in patients treated by surgery or chemotherapy by 16S rRNA sequencing reveals potential biomarkers for colorectal cancer therapy. Front Microbiol. 2018;9:1607.
   PubMed Web of Science ®Google Scholar
• Yan X, Liu L, Li H, et al. Clinical significance of Fusobacterium nucleatum, epithelial-mesenchymal transition, and cancer stem cell markers in stage III/IV colorectal cancer patients. Onco Targets Ther. 2017;10:5031–5046.
   PubMed Web of Science ®Google Scholar
• Wei Z, Cao S, Liu S, et al. Could gut microbiota serve as prognostic biomarker associated with colorectal cancer patients’ survival? A pilot study on relevant mechanism. Oncotarget. 2016;7(29):46158–46172.
   PubMedGoogle Scholar
• Mima K, Nishihara R, Qian ZR, et al. Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis. Gut. 2016;65(12):1973–1980.
   PubMed Web of Science ®Google Scholar
• 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(8):1381–1390.
   PubMed Web of Science ®Google Scholar
• Iida N, Mizukoshi E, Yamashita T, et al. Overuse of antianaerobic drug is associated with poor postchemotherapy prognosis of patients with hepatocellular carcinoma. Int J Cancer. 2019. DOI:10.1002/ijc.32339
   PubMed Web of Science ®Google Scholar
• Viaud S, Saccheri F, Mignot G, et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science. 2013;342(6161):971–976.
   PubMed Web of Science ®Google Scholar
• Wilson ID, Nicholson JK. Gut microbiome interactions with drug metabolism, efficacy, and toxicity. Transl Res. 2017;179:204–222.
   PubMed Web of Science ®Google Scholar
• Brennan CA, Garrett WS. Fusobacterium nucleatum - symbiont, opportunist and oncobacterium. Nat Rev Microbiol. 2019;17(3):156–166.
   PubMed Web of Science ®Google Scholar
• Allen-Vercoe E, Jobin C. Fusobacterium and Enterobacteriaceae: important players for CRC?. Immunol Lett. 2014;162(2Pt A):54–61.
   PubMedGoogle Scholar
• Gur C, Maalouf N, Shhadeh A, et al. Fusobacterium nucleatum suppresses anti-tumor immunity by activating CEACAM1. Oncoimmunology. 2019;8(6):e1581531.
   PubMed Web of Science ®Google Scholar
• Rubinstein MR, Wang X, Liu W, et al. Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesin. Cell Host Microbe. 2013;14(2):195–206.
   PubMed Web of Science ®Google Scholar
• Gur C, Ibrahim Y, Isaacson B, et al. Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack. Immunity. 2015;42(2):344–355.
   PubMed Web of Science ®Google Scholar
• Yu T, Guo F, Yu Y, et al. Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy. Cell. 2017;170(3):548–563.e16.
   PubMed Web of Science ®Google Scholar
• Haruki K, Kosumi K, Hamada T, et al. Association of autophagy status with amount of Fusobacterium nucleatum in colorectal cancer. J Pathol. 2020;250(4):397–408.
   PubMed Web of Science ®Google Scholar
• Li YJ, Lei YH, Yao N, et al. Autophagy and multidrug resistance in cancer. Chin J Cancer. 2017;36(1):52.
   PubMedGoogle Scholar
• Auberger P, Puissant A. Autophagy, a key mechanism of oncogenesis and resistance in leukemia. Blood. 2017;129(5):547–552.
   PubMed Web of Science ®Google Scholar
• Yun CW, Lee SH. The roles of autophagy in cancer. Int J Mol Sci. 2018;19(11):3466.
   PubMed Web of Science ®Google Scholar
• Smith AG, Macleod KF. Autophagy, cancer stem cells and drug resistance. J Pathol. 2019;247(5):708–718.
   PubMed Web of Science ®Google Scholar
• Sosa MS, Bragado P, Aguirre-Ghiso JA. Mechanisms of disseminated cancer cell dormancy: an awakening field. Nat Rev Cancer. 2014;14(9):611–622.
   PubMed Web of Science ®Google Scholar
• Leystra AA, Clapper ML. Gut microbiota influences experimental outcomes in mouse models of colorectal cancer. Genes (Basel). 2019;10(11):900.
   PubMed Web of Science ®Google Scholar
• Nguyen TL, Vieira-Silva S, Liston A, et al. How informative is the mouse for human gut microbiota research?. Dis Model Mech. 2015;8(1):1–16.
   PubMed Web of Science ®Google Scholar
• Gupta VK, Paul S, Dutta C. Geography ethnicity or subsistence-specific variations in human microbiome composition and diversity. Front Microbiol. 2017;8:1162.
   PubMed Web of Science ®Google Scholar
• Sharma A, Buschmann MM, Gilbert JA. Pharmacomicrobiomics: the holy grail to variability in drug response?. Clin Pharmacol Ther. 2019;106(2):317–328.
   PubMed Web of Science ®Google Scholar
• Fukuda S, Toh H, Hase K, et al. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature. 2011;469:543–547.
   PubMed Web of Science ®Google Scholar
• Jenq RR, Taur Y, Devlin SM, et al. Intestinal blautia is associated with reduced death from graft-versus-host disease. Biol Blood Marrow Transplant. 2015;21(8):1373–1383.
   PubMed Web of Science ®Google Scholar
• Mathewson ND, Jenq R, Mathew AV, et al. Gut microbiome-derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease [published correction appears in Nat Immunol. 2016;17(10):1235]. Nat Immunol. 2016;17(5):505–513.
   PubMed Web of Science ®Google Scholar
• Furusawa Y, Obata Y, Fukuda S, et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013;504:446–450.
   PubMed Web of Science ®Google Scholar
• Arpaia N, Campbell C, Fan X, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 2013;504:451–455.
   PubMed Web of Science ®Google Scholar
• Tan J, McKenzie C, Potamitis M, et al. The role of short-chain fatty acids in health and disease. Adv Immunol. 2014;121:91–119.
   PubMed Web of Science ®Google Scholar
• Sivaprakasam S, Prasad PD, Singh N. Benefits of short-chain fatty acids and their receptors in inflammation and carcinogenesis. Pharmacol Ther. 2016;164:144–151.
   PubMed Web of Science ®Google Scholar
• Gheldof A, Berx G. Cadherins and epithelial-to-mesenchymal transition. Prog Mol Biol Transl Sci. 2013;116:317–336.
   PubMed Web of Science ®Google Scholar
• Pal M, Bhattacharya S, Kalyan G, et al. Cadherin profiling for therapeutic interventions in Epithelial Mesenchymal Transition (EMT) and tumorigenesis. Exp Cell Res. 2018;368(2):137–146.
   PubMed Web of Science ®Google Scholar
• Mrozik KM, Blaschuk OW, Cheong CM, et al. N-cadherin in cancer metastasis, its emerging role in haematological malignancies and potential as a therapeutic target in cancer. BMC Cancer. 2018 Oct 1;18(1):939.
   PubMedGoogle Scholar
• Luo Y, Yu T, Zhang Q, et al. Upregulated N-cadherin expression is associated with poor prognosis in epithelial-derived solid tumours: A meta-analysis. Eur J Clin Invest. 2018;48(4):e12903.
   Web of Science ®Google Scholar
• Grohmann A, Tanneberger K, Alzner A, et al. AMER1 regulates the distribution of the tumor suppressor APC between microtubules and the plasma membrane. J Cell Sci. 2007;120(Pt 21):3738–3747.
   PubMed Web of Science ®Google Scholar
• Choi M, Kipps T, Kurzrock R. ATM mutations in cancer: therapeutic Implications. Mol Cancer Ther. 2016;15(8):1781–1791.
   PubMed Web of Science ®Google Scholar
• Gethings-Behncke C, Coleman HG, Jordao HWT, et al. Fusobacterium nucleatum in the colorectum and its association with cancer risk and survival: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2020;29(3):539–548.
   PubMed Web of Science ®Google Scholar
• Luke JJ, Flaherty KT, Ribas A, et al. Targeted agents and immunotherapies: optimizing outcomes in melanoma. Nat Rev Clin Oncol. 2017;14(8):463–482.
   PubMed Web of Science ®Google Scholar
• Schachter J, Ribas A, Long GV, et al. Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006). Lancet. 2017;390(10105):1853–1862.
   PubMed Web of Science ®Google Scholar
• Ellis PM, Vella ET, Ung YC. Immune checkpoint inhibitors for patients with advanced non-small-cell lung cancer: a systematic review. Clin Lung Cancer. 2017;18(5):444–459.e1.
   PubMed Web of Science ®Google Scholar
• Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018;378(22):2078–2092.
   PubMed Web of Science ®Google Scholar
• Havel JJ, Chowell D, Chan TA. The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy. Nat Rev Cancer. 2019;19(3):133–150.
   PubMed Web of Science ®Google Scholar
• Darvin P, Toor SM, Sasidharan Nair V, et al. Immune checkpoint inhibitors: recent progress and potential biomarkers. Exp Mol Med. 2018 Dec 13;50(12):165.
   PubMedGoogle Scholar
• Gong J, Chehrazi-Raffle A, Placencio-Hickok V, et al. The gut microbiome and response to immune checkpoint inhibitors: preclinical and clinical strategies. Clin Transl Med. 2019;8(1):9.
   PubMedGoogle Scholar
• Ma C, Han M, Heinrich B, et al. Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells. Science. 2018;360(6391):eaan5931.
   PubMed Web of Science ®Google Scholar
• Pitt JM, Vétizou M, Waldschmitt N, et al. Fine-tuning cancer immunotherapy: optimizing the gut microbiome. Cancer Res. 2016;76(16):4602–4607.
   PubMed Web of Science ®Google Scholar
• Gately S. Human microbiota and personalized cancer treatments: role of commensal microbes in treatment outcomes for cancer patients. Cancer Treat Res. 2019;178:253–264.
   PubMedGoogle Scholar
• Chalabi M, Cardona A, Nagarkar DR, et al. Efficacy of chemotherapy and atezolizumab in patients with non-small-cell lung cancer receiving antibiotics and proton pump inhibitors: pooled post hoc analyses of the OAK and POPLAR trials. Ann Oncol. 2020;31(4):525–531.
   PubMed Web of Science ®Google Scholar
• Jin Y, Dong H, Xia L, et al. The diversity of gut microbiome is associated with favorable responses to anti-PD-1 immunotherapy in Chinese Patients with NSCLC. J Thorac Oncol. 2019;14(8):1378–1389. DOI:10.1016/j.jtho.2019.04.007
   Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Chaput N, Lepage P, Coutzac C, et al. Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab. Ann Oncol. 2017;28(6):1368–1379.
   PubMed Web of Science ®Google Scholar
• Frankel AE, Coughlin LA, Kim J, et al. Metagenomic shotgun sequencing and unbiased metabolomic profiling identify specific human gut microbiota and metabolites associated with immune checkpoint therapy efficacy in melanoma patients. Neoplasia. 2017;19(10):848–855.
   PubMed Web of Science ®Google Scholar
• Sivan A, Corrales L, Hubert N, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015;350(6264):1084–1089.
   PubMed Web of Science ®Google Scholar
• Vétizou M, Pitt JM, Daillère R, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015;350(6264):1079–1084.
   PubMed Web of Science ®Google Scholar
• Yoshii K, Hosomi K, Sawane K, et al. Metabolism of dietary and microbial vitamin b family in the regulation of host immunity. Front Nutr. 2019;6:48.
   PubMed Web of Science ®Google Scholar
• Tian Y, Abu-Sbeih H, Wang Y. Immune checkpoint inhibitors-induced colitis. Adv Exp Med Biol. 2018;995:151–157.
   PubMed Web of Science ®Google Scholar
• Rooks MG, Garrett WS. Gut microbiota, metabolites and host immunity. Nat Rev Immunol. 2016;16(6):341–352.
   PubMed Web of Science ®Google Scholar
• Kim CH. Immune regulation by microbiome metabolites. Immunology. 2018;154(2):220–229.
   PubMed Web of Science ®Google Scholar
• Gnanaprakasam JNR, Estrada-Muñiz E, Vega L. The anacardic 6-pentadecyl salicylic acid induces macrophage activation via the phosphorylation of ERK1/2, JNK, P38 kinases and NF-κB. Int Immunopharmacol. 2015;29(2):808–817.
   PubMed Web of Science ®Google Scholar
• Hollands A, Corriden R, Gysler G, et al. Natural product anacardic acid from cashew nut shells stimulates neutrophil extracellular trap production and bactericidal activity. J Biol Chem. 2016;291(27):13964–13973.
   PubMed Web of Science ®Google Scholar
• Hemshekhar M, Sebastin Santhosh M, Kemparaju K, et al. Emerging roles of anacardic acid and its derivatives: a pharmacological overview. Basic Clin Pharmacol Toxicol. 2012;110(2):122–132.
   PubMed Web of Science ®Google Scholar
• Shitara K, Nishikawa H. Regulatory T cells: a potential target in cancer immunotherapy. Ann N Y Acad Sci. 2018;1417(1):104–115.
   PubMed Web of Science ®Google Scholar
• Tanaka A, Sakaguchi S. Regulatory T cells in cancer immunotherapy. Cell Res. 2017;27(1):109–118.
   PubMed Web of Science ®Google Scholar
• Blacher E, Levy M, Tatirovsky E, et al. Microbiome-modulated metabolites at the interface of host immunity. J Immunol. 2017;198(2):572–580.
   PubMed Web of Science ®Google Scholar
• Wang G, Huang S, Wang Y, et al. Bridging intestinal immunity and gut microbiota by metabolites [published online ahead of print, 2019 Jun 27]. Cell Mol Life Sci. 2019. DOI:10.1007/s00018-019-03190-6
   Web of Science ®Google Scholar
• Reese AT, Dunn RR. Drivers of microbiome biodiversity: a review of general rules, feces, and ignorance. mBio. 2018;9(4):e01294–18.
   PubMed Web of Science ®Google Scholar
• Wilson BE, Routy B, Nagrial A, et al. The effect of antibiotics on clinical outcomes in immune-checkpoint blockade: a systematic review and meta-analysis of observational studies. Cancer Immunol Immunother. 2020;69(3):343–354.
   PubMed Web of Science ®Google Scholar
• Hajjar R, Santos MM, Dagbert F, et al. Current evidence on the relation between gut microbiota and intestinal anastomotic leak in colorectal surgery [published online ahead of print, 2019 Jul 11]. Am J Surg. 2019. S0002-9610(19)30197-7. DOI:10.1016/j.amjsurg.2019.07.001
   PubMed Web of Science ®Google Scholar
• McDermott FD, Heeney A, Kelly ME, et al. Systematic review of preoperative, intraoperative and postoperative risk factors for colorectal anastomotic leaks. Br J Surg. 2015;102(5):462–479.
   PubMed Web of Science ®Google Scholar
• Gershuni VM, Friedman ES. The microbiome-host interaction as a potential driver of anastomotic leak. Curr Gastroenterol Rep. 2019 Jan 26;21(1):4.
   PubMedGoogle Scholar
• Guyton K, Alverdy JC. The gut microbiota and gastrointestinal surgery. Nat Rev Gastroenterol Hepatol. 2017;14(1):43–54.
   PubMed Web of Science ®Google Scholar
• Wang S, Liu J, Wang S, et al. Adverse effects of anastomotic leakage on local recurrence and survival after curative anterior resection for rectal cancer: a systematic review and meta-analysis. World J Surg. 2017;41(1):277–284.
   PubMed Web of Science ®Google Scholar
• Gessler B, Eriksson O, Angenete E. Diagnosis, treatment, and consequences of anastomotic leakage in colorectal surgery. Int J Colorectal Dis. 2017;32(4):549–556.
   PubMed Web of Science ®Google Scholar
• van Praagh JB, de Goffau MC, Bakker IS, et al. Mucus microbiome of anastomotic tissue during surgery has predictive value for colorectal anastomotic leakage. Ann Surg. 2019;269(5):911–916.
   PubMed Web of Science ®Google Scholar
• Reddy RM, Weir WB, Barnett S, et al. Increased variance in oral and gastric microbiome correlates with esophagectomy anastomotic leak. Ann Thorac Surg. 2018;105(3):865–870.
   PubMed Web of Science ®Google Scholar
• Shakhsheer BA, Versten LA, Luo JN, et al. Morphine promotes colonization of anastomotic tissues with collagenase - producing enterococcus faecalis and causes leak. J Gastrointest Surg. 2016;20(10):1744–1751.
   PubMed Web of Science ®Google Scholar
• van Praagh JB, de Goffau MC, Bakker IS, et al. Intestinal microbiota and anastomotic leakage of stapled colorectal anastomoses: a pilot study. Surg Endosc. 2016;30(6):2259–2265.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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(8):e44326.
   PubMed Web of Science ®Google Scholar
• Kornmann VN, van Ramshorst B, Smits AB, et al. Beware of false-negative CT scan for anastomotic leakage after colonic surgery. Int J Colorectal Dis. 2014;29(4):445–451.
   PubMed Web of Science ®Google Scholar
• Marres CCM, van de Ven AWH, Leijssen LGJ, et al. Colorectal anastomotic leak: delay in reintervention after false-negative computed tomography scan is a reason for concern. Tech Coloproctol. 2017;21(9):709–714.
   PubMed Web of Science ®Google Scholar
• Babrowski T, Holbrook C, Moss J, et al. Pseudomonas aeruginosa virulence expression is directly activated by morphine and is capable of causing lethal gut-derived sepsis in mice during chronic morphine administration. Ann Surg. 2012;255(2):386–393.
   PubMed Web of Science ®Google Scholar
• Rawlinson A, Kang P, Evans J, et al. A systematic review of enhanced recovery protocols in colorectal surgery. Ann R Coll Surg Engl. 2011;93(8):583–588.
   PubMed Web of Science ®Google Scholar
• Bakker IS, Morks AN, Ten Cate Hoedemaker HO, et al. Randomized clinical trial of biodegradable intraluminal sheath to prevent anastomotic leak after stapled colorectal anastomosis. Br J Surg. 2017;104(8):1010–1019.
   PubMed Web of Science ®Google Scholar
• Bakker IS, Morks AN, Hoedemaker HO, et al. The C-seal trial: colorectal anastomosis protected by a biodegradable drain fixed to the anastomosis by a circular stapler, a multi-center randomized controlled trial. BMC Surg. 2012;12:23.
   PubMed Web of Science ®Google Scholar
• Palmgren Colov E, Helene Degett T, Raskov H, et al. The impact of the gut microbiota on prognosis after surgery for colorectal cancer - a systematic review and meta-analysis [published online ahead of print, 2020 Feb 4]. APMIS. 2020. DOI:10.1111/apm.13032
   Web of Science ®Google Scholar
• Sonnenburg ED, Smits SA, Tikhonov M, et al. Diet-induced extinctions in the gut microbiota compound over generations. Nature. 2016;529(7585):212–215.
   PubMed Web of Science ®Google Scholar
• Yamada T, Takahashi D, Hase K. The diet-microbiota-metabolite axis regulates the host physiology. J Biochem. 2016;160(1):1–10.
   PubMed Web of Science ®Google Scholar
• Tomasello G, Mazzola M, Leone A, et al. Nutrition, oxidative stress and intestinal dysbiosis: influence of diet on gut microbiota in inflammatory bowel diseases. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2016;160(4):461–466.
   PubMed Web of Science ®Google Scholar
• Martinez KB, Leone V, Chang EB. Western diets, gut dysbiosis, and metabolic diseases: are they linked?. Gut Microbes. 2017;8(2):130–142.
   PubMed Web of Science ®Google Scholar
• Kurilshikov A, Wijmenga C, Fu J, et al. Host genetics and gut microbiome: challenges and perspectives. Trends Immunol. 2017;38(9):633–647.
   PubMed Web of Science ®Google Scholar
• Dąbrowska K, Witkiewicz W. Correlations of host genetics and gut microbiome composition. Front Microbiol. 2016;7(1357). DOI:10.3389/fmicb.2016.01357.
   Google Scholar
• Gomes AC, Hoffmann C, Mota JF. The human gut microbiota: metabolism and perspective in obesity. Gut Microbes. 2018;9(4):308–325.
   PubMed Web of Science ®Google Scholar
• Capurso G, Lahner E. The interaction between smoking, alcohol and the gut microbiome. Best Pract Res Clin Gastroenterol. 2017;31(5):579–588.
   PubMed Web of Science ®Google Scholar
• Dominguez-Bello MG, Godoy-Vitorino F, Knight R, et al. Role of the microbiome in human development. Gut. 2019;68(6):1108–1114.
   PubMed Web of Science ®Google Scholar
• Mokkala K, Houttu N, Cansev T, et al. Interactions of dietary fat with the gut microbiota: evaluation of mechanisms and metabolic consequences. Clin Nutr. 2019. S0261-5614(19)30214-6. DOI:10.1016/j.clnu.2019.05.003
   Web of Science ®Google Scholar
• Ramírez-Pérez O, Cruz-Ramón V, Chinchilla-López P, et al. The role of the gut microbiota in bile acid metabolism. Ann Hepatol. 2017;16(Suppl. 1: s3–105.):s15–s20.
   PubMedGoogle Scholar
• Bibbò S, Ianiro G, Giorgio V, et al. The role of diet on gut microbiota composition. Eur Rev Med Pharmacol Sci. 2016;20(22):4742–4749.
   PubMed Web of Science ®Google Scholar
• Singh RK, Chang HW, Yan D, et al. Influence of diet on the gut microbiome and implications for human health. J Transl Med. 2017;15(1):73.
   PubMed Web of Science ®Google Scholar
• Jeffery IB, O’Toole PW. Diet-microbiota interactions and their implications for healthy living. Nutrients. 2013 Jan 17;5(1):234–252.
   PubMed Web of Science ®Google Scholar
• Shuwen H, Miao D, Quan Q, et al. Protective effect of the “food-microorganism-SCFAs” axis on colorectal cancer: from basic research to practical application. J Cancer Res Clin Oncol. 2019;145(9):2169–2197.
   PubMed Web of Science ®Google Scholar
• Brun P, Castagliuolo I, Di Leo V, et al. intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol. 2007;292(2):G518–G525.
   PubMed Web of Science ®Google Scholar
• De Almeida CV, de Camargo MR, Russo E, et al. Role of diet and gut microbiota on colorectal cancer immunomodulation. World J Gastroenterol. 2019;25(2):151–162.
   PubMed Web of Science ®Google Scholar
• Mehta RS, Song M, Nishihara R, et al. Dietary patterns and risk of colorectal cancer: analysis by tumor location and molecular subtypes. Gastroenterology. 2017;152(8):1944–1953.e1.
   PubMed Web of Science ®Google Scholar
• Feng YL, Shu L, Zheng PF, et al. Dietary patterns and colorectal cancer risk: a meta-analysis. Eur J Cancer Prev. 2017;26(3):201–211.
   PubMed Web of Science ®Google Scholar
• Stärkel P, Leclercq S, de Timary P, et al. Intestinal dysbiosis and permeability: the yin and yang in alcohol dependence and alcoholic liver disease. Clin Sci (Lond). 2018;132(2):199–212.
   PubMed Web of Science ®Google Scholar
• Engen PA, Green SJ, Voigt RM, et al. The gastrointestinal microbiome: alcohol effects on the composition of intestinal microbiota. Alcohol Res. 2015;37(2):223–236.
   PubMed Web of Science ®Google Scholar
• Llopis M, Cassard AM, Wrzosek L, et al. Intestinal microbiota contributes to individual susceptibility to alcoholic liver disease. Gut. 2016;65(5):830–839.
   PubMed Web of Science ®Google Scholar
• Jiang Z, Jacob JA, Li J, et al. Influence of diet and dietary nanoparticles on gut dysbiosis. Microb Pathog. 2018;118:61–65.
   PubMed Web of Science ®Google Scholar
• Neuman H, Forsythe P, Uzan A, et al. Antibiotics in early life: dysbiosis and the damage done. FEMS Microbiol Rev. 2018;42(4):489–499.
   PubMed Web of Science ®Google Scholar
• Van Raay T, Allen-Vercoe E. Microbial interactions and interventions in colorectal cancer. Microbiol Spectr. 2017;5(3). DOI:10.1128/microbiolspec.BAD-0004-2016
   PubMed Web of Science ®Google Scholar
• Zhang J, Haines C, Watson AJM, et al. Oral antibiotic use and risk of colorectal cancer in the United Kingdom, 1989-2012: a matched case-control study. Gut. 2019. DOI:10.1136/gutjnl-2019-318593
   Web of Science ®Google Scholar
• Daniel CR, McQuade JL. Nutrition and cancer in the microbiome era. Trends Cancer. 2019;5(9):521–524.
   PubMed Web of Science ®Google Scholar
• Xie Y, Zhao Y, Shi L, et al. Gut epithelial TSC1/mTOR controls RIPK3-dependent necroptosis in intestinal inflammation and cancer [published online ahead of print, 2020 Mar 16]. J Clin Invest. 2020;133264. DOI:10.1172/JCI133264
   PubMed Web of Science ®Google Scholar
• Elinav E, Garrett WS, Trinchieri G, et al. The cancer microbiome. Nat Rev Cancer. 2019;19(7):371–376.
   PubMed Web of Science ®Google Scholar
• Beiko RG, Hsiao W, Parkinson J. Microbiome analysis: methods and protocols. New York, NY: Humana Press; 2018. DOI:10.1007/978-1-4939-8728-3
   Google Scholar
• Raskov H, Burcharth J, Pommergaard HC. Linking gut microbiota to colorectal cancer. J Cancer. 2017;8(17):3378–3395.
   PubMed Web of Science ®Google Scholar
• Saus E, Iraola-Guzmán S, Willis JR, et al. Microbiome and colorectal cancer: roles in carcinogenesis and clinical potential. Mol Aspects Med. 2019. S0098-2997(19)30032-9. DOI:10.1016/j.mam.2019.05.001
   PubMed Web of Science ®Google Scholar
• Flemer B, Lynch DB, Brown JM, et al. Tumour-associated and non-tumour-associated microbiota in colorectal cancer. Gut. 2017;66(4):633–643.
   PubMed Web of Science ®Google Scholar
• Nené NR, Reisel D, Leimbach A, et al. Association between the cervicovaginal microbiome, BRCA1 mutation status, and risk of ovarian cancer: a case-control study. Lancet Oncol. 2019;20(8):1171–1182.
   PubMed Web of Science ®Google Scholar
• Mani S. Microbiota and breast cancer. Prog Mol Biol Transl Sci. 2017;151:217–229.
   PubMed Web of Science ®Google Scholar
• Fernández MF, Reina-Pérez I, Astorga JM, et al. Breast cancer and its relationship with the microbiota. Int J Environ Res Public Health. 2018;15(8):1747.
   Web of Science ®Google Scholar
• Michaud DS, Izard J. Microbiota, oral microbiome, and pancreatic cancer. Cancer J. 2014;20(3):203–206.
   PubMed Web of Science ®Google Scholar
• Mima K, Nakagawa S, Sawayama H, et al. The microbiome and hepatobiliary-pancreatic cancers. Cancer Lett. 2017;402:9–15.
   PubMed Web of Science ®Google Scholar
• Bullman S, Pedamallu CS, Sicinska E, et al. Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Science. 2017;358(6369):1443–1448.
   PubMed Web of Science ®Google Scholar
• Mandal P. Molecular mechanistic pathway of colorectal carcinogenesis associated with intestinal microbiota. Anaerobe. 2018;49:63–70.
   PubMed Web of Science ®Google Scholar
• Alexander JL, Scott AJ, Pouncey AL, et al. Colorectal carcinogenesis: an archetype of gut microbiota-host interaction. Ecancermedicalscience. 2018;12:865.
   PubMed Web of Science ®Google Scholar
• Tilg H, Adolph TE, Gerner RR, et al. The intestinal microbiota in colorectal cancer. Cancer Cell. 2018;33(6):954–964.
   PubMed Web of Science ®Google Scholar
• Cogdill AP, Gaudreau PO, Arora R, et al. The impact of intratumoral and gastrointestinal microbiota on systemic cancer therapy. Trends Immunol. 2018;39(11):900–920.
   PubMed Web of Science ®Google Scholar
• Geller LT, Barzily-Rokni M, Danino T, et al. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. Science. 2017;357(6356):1156–1160.
   PubMed Web of Science ®Google Scholar
• Gaines S, Shao C, Hyman N, et al. Gut microbiome influences on anastomotic leak and recurrence rates following colorectal cancer surgery. Br J Surg. 2018;105(2):e131–e141.
   PubMed Web of Science ®Google Scholar
• Skonieczna-Żydecka K, Kaczmarczyk M, Łoniewski I, et al. A systematic review, meta-analysis, and meta-regression evaluating the efficacy and mechanisms of action of probiotics and synbiotics in the prevention of surgical site infections and surgery-related complications. J Clin Med. 2018;7(12):556.
   Web of Science ®Google Scholar
• Zhu W, Miyata N, Winter MG, et al. Editing of the gut microbiota reduces carcinogenesis in mouse models of colitis-associated colorectal cancer [published online ahead of print, 2019 Jul 29]. J Exp Med. 2019. DOI:10.1084/jem.20181939
   Web of Science ®Google Scholar
• Uccello M, Malaguarnera G, Basile F, et al. Potential role of probiotics on colorectal cancer prevention. BMC Surg. 2012;12 Suppl 1(Suppl1):S35.
   PubMedGoogle Scholar
• Eslami M, Yousefi B, Kokhaei P, et al. Importance of probiotics in the prevention and treatment of colorectal cancer. J Cell Physiol. 2019;234(10):17127–17143.
   PubMed Web of Science ®Google Scholar
• Riquelme E, Zhang Y, Zhang L, et al. Tumor microbiome diversity and composition influence pancreatic cancer outcomes. Cell. 2019;178(4):795–806.e12.
   PubMed Web of Science ®Google Scholar
• Charalampous T, Kay GL, Richardson H, et al. Nanopore metagenomics enables rapid clinical diagnosis of bacterial lower respiratory infection. Nat Biotechnol. 2019;37(7):783–792.
   PubMed Web of Science ®Google Scholar
• Sheth RU, Li M, Jiang W, et al. Spatial metagenomic characterization of microbial biogeography in the gut. Nat Biotechnol. 2019. DOI:10.1038/s41587-019-0183-2
   PubMed Web of Science ®Google Scholar
• Integrative HMP (iHMP) Research Network Consortium. The integrative human microbiome project. Nature. 2019;569(7758):641–648.
   PubMed Web of Science ®Google Scholar
• Aragonès G, Colom-Pellicer M, Aguilar C, et al. Circulating microbiota-derived metabolites: a “liquid biopsy?. Int J Obes (Lond). 2019. DOI:10.1038/s41366-019-0430-0
   PubMed Web of Science ®Google Scholar
• Kunzmann AT, Proença MA, Jordao HW, et al. Fusobacterium nucleatum tumor DNA levels are associated with survival in colorectal cancer patients. Eur J Clin Microbiol Infect Dis. 2019. DOI:10.1007/s10096-019-03649-1
   PubMed Web of Science ®Google Scholar
• Pinato DJ, Howlett S, Ottaviani D, et al. Association of prior antibiotic treatment with survival and response to immune checkpoint inhibitor therapy in patients with cancer. JAMA Oncol. 2019. DOI:10.1001/jamaoncol.2019.2785
   PubMed Web of Science ®Google Scholar
• Roumpeka DD, Wallace RJ, Escalettes F, et al. A review of bioinformatics tools for bio-prospecting from metagenomic sequence data. Front Genet. 2017;8:23.
   PubMed Web of Science ®Google Scholar
• Jünemann S, Kleinbölting N, Jaenicke S, et al. Bioinformatics for NGS-based metagenomics and the application to biogas research. J Biotechnol. 2017;261:10–23.
   PubMed Web of Science ®Google Scholar
• Brożek JL, Akl EA, Compalati E, et al. Grading quality of evidence and strength of recommendations in clinical practice guidelines part 3 of 3. The GRADE approach to developing recommendations. Allergy. 2011;66(5):588–595.
   PubMed Web of Science ®Google Scholar
• Hsu J, Brożek JL, Terracciano L, et al. Application of GRADE: making evidence-based recommendations about diagnostic tests in clinical practice guidelines. Implement Sci. 2011;6:62.
   PubMed Web of Science ®Google Scholar
• Neumann I, Brignardello-Petersen R, Wiercioch W, et al. The GRADE evidence-to-decision framework: a report of its testing and application in 15 international guideline panels. Implement Sci. 2016;11:93.
   PubMed Web of Science ®Google Scholar
• Veziant J, Poirot K, Chevarin C, et al. Prognostic value of a combination of innovative factors (gut microbiota, sarcopenia, obesity, metabolic syndrome) to predict surgical/oncologic outcomes following surgery for sporadic colorectal cancer: a prospective cohort study protocol (METABIOTE). BMJ Open. 2020;10(1):e031472.
   PubMed Web of Science ®Google Scholar
• Yang J, Tan Q, Fu Q, et al. Gastrointestinal microbiome and breast cancer: correlations, mechanisms and potential clinical implications. Breast Cancer. 2017;24(2):220–228.
   PubMed Web of Science ®Google Scholar
• Li Y, Elmén L, Segota I, et al. Prebiotic-induced anti-tumor immunity attenuates tumor growth. Cell Rep. 2020;30(6):1753–1766.e6.
   PubMed Web of Science ®Google Scholar
• Suzuki TA, Worobey M. Geographical variation of human gut microbial composition. Biol Lett. 2014;10(2):20131037.
   PubMed Web of Science ®Google Scholar
• Smits LP, Bouter KE, de Vos WM, et al. Therapeutic potential of fecal microbiota transplantation. Gastroenterology. 2013;145(5):946–953.
   PubMed Web of Science ®Google Scholar
• [cited 2020 Mar 25]. Available from: https://patents.google.com/?q=cancer+gut+microbiota&oq=cancer+gut+microbiota+
   Google Scholar
• Green D, Lavesson N. Chaos theory and artificial intelligence may provide insights on disability outcomes. Dev Med Child Neurol. 2019;61(10):1120.
   PubMed Web of Science ®Google Scholar
• Hamada T, Keum N, Nishihara R, et al. Molecular pathological epidemiology: new developing frontiers of big data science to study etiologies and pathogenesis. J Gastroenterol. 2017;52(3):265–275.
   PubMed Web of Science ®Google Scholar
• Nishi A, Kawachi I, Koenen KC, et al. Lifecourse epidemiology and molecular pathological epidemiology. Am J Prev Med. 2015;48(1):116–119.
   PubMed Web of Science ®Google Scholar
• Ogino S, Nowak JA, Hamada T, et al. Insights into pathogenic interactions among environment, host, and tumor at the crossroads of molecular pathology and epidemiology. Annu Rev Pathol. 2019;14:83–103.
   PubMed Web of Science ®Google Scholar
• Scott AJ, Alexander JL, Merrifield CA, et al. International cancer microbiome consortium consensus statement on the role of the human microbiome in carcinogenesis. Gut. 2019;68(9):1624–1632.
   PubMed Web of Science ®Google Scholar
• Aykut B, Pushalkar S, Chen R, et al. The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL. Nature. 2019;574(7777):264–267.
   PubMed Web of Science ®Google Scholar