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World Journal of Surgical Oncology
Published in: World Journal of Surgical Oncology 1/2019

Open Access 01-12-2019 | Colorectal Cancer | Review

Role of the intestinal microbiome in colorectal cancer surgery outcomes

Authors: Lelde Lauka, Elisa Reitano, Maria Clotilde Carra, Federica Gaiani, Paschalis Gavriilidis, Francesco Brunetti, Gian Luigi de’Angelis, Iradj Sobhani, Nicola de’Angelis

Published in: World Journal of Surgical Oncology | Issue 1/2019

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Abstract

Objectives

Growing evidence supports the role of the intestinal microbiome in the carcinogenesis of colorectal cancers, but its impact on colorectal cancer surgery outcomes is not clearly defined. This systematic review aimed to analyze the association between intestinal microbiome composition and postoperative complication and survival following colorectal cancer surgery.

Methods

A systematic review was conducted according to the 2009 PRISMA guidelines. Two independent reviewers searched the literature in a systematic manner through online databases, including Medline, Scopus, Embase, Cochrane Oral Health Group Specialized Register, ProQuest Dissertations and Theses Database, and Google Scholar. Human studies investigating the association between the intestinal microbiome and the short-term (anastomotic leakage, surgical site infection, postoperative ileus) and long-term outcomes (cancer-specific mortality, overall and disease-free survival) of colorectal cancer surgery were selected. Patients with any stage of colorectal cancer were included. The Newcastle-Ottawa scale for case-control and cohort studies was used for the quality assessment of the selected articles.

Results

Overall, 8 studies (7 cohort studies and 1 case-control) published between 2014 and 2018 were included. Only one study focused on short-term surgical outcomes, showing that anastomotic leakage is associated with low microbial diversity and abundance of Lachnospiraceae and Bacteroidaceae families in the non-cancerous resection lines of the stapled anastomoses of colorectal cancer patients. The other 7 studies focused on long-term oncological outcomes, including survival and cancer recurrence. The majority of the studies (5/8) found that a higher level of Fusobacterium nucleatum adherent to the tumor tissue is associated with worse oncological outcomes, in particular, increased cancer-specific mortality, decreased median and overall survival, disease-free and cancer-specific survival rates. Also a high abundance of Bacteroides fragilis was found to be linked to worse outcomes, whereas the relative abundance of the Prevotella-co-abundance group (CAG), the Bacteroides CAG, and the pathogen CAG as well as Faecalibacterium prausnitzii appeared to be associated with better survival.

Conclusions

Based on the limited available evidence, microbiome composition may be associated with colorectal cancer surgery outcomes. Further studies are needed to elucidate the role of the intestinal microbiome as a prognostic factor in colorectal cancer surgery and its possible clinical implications.
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Literature
1.
Jalanka-Tuovinen J, Salonen A, Nikkila J, Immonen O, Kekkonen R, Lahti L, et al. Intestinal microbiota in healthy adults: temporal analysis reveals individual and common core and relation to intestinal symptoms. PLoS One. 2011;6(7):e23035.PubMedPubMedCentralCrossRef
2.
Morowitz MJ, Babrowski T, Carlisle EM, Olivas A, Romanowski KS, Seal JB, et al. The human microbiome and surgical disease. Ann Surg. 2011;253(6):1094–101.PubMedCrossRef
3.
Lin C, Cai X, Zhang J, Wang W, Sheng Q, Hua H, et al. Role of gut microbiota in the development and treatment of colorectal cancer. Digestion. 2019;100(1):72–8.PubMedCrossRef
4.
Ralls MW, Miyasaka E, Teitelbaum DH. Intestinal microbial diversity and perioperative complications. JPEN J Parenter Enteral Nutr. 2014;38(3):392–9.PubMedCrossRef
5.
Bachmann R, Leonard D, Delzenne N, Kartheuser A, Cani PD. Novel insight into the role of microbiota in colorectal surgery. Gut. 2017;66(4):738–49.PubMedCrossRef
6.
Arvans DL, Vavricka SR, Ren H, Musch MW, Kang L, Rocha FG, et al. Luminal bacterial flora determines physiological expression of intestinal epithelial cytoprotective heat shock proteins 25 and 72. Am J Physiol Gastrointest Liver Physiol. 2005;288(4):G696–704.PubMedCrossRef
7.
Alverdy JC. Ionic modulation of bacterial virulence and its role in surgical infection. Surg Infect. 2018;19(8):769–73.CrossRef
8.
Souza DG, Vieira AT, Soares AC, Pinho V, Nicoli JR, Vieira LQ, et al. The essential role of the intestinal microbiota in facilitating acute inflammatory responses. J Immunol (Baltimore, Md : 1950). 2004;173(6):4137-4146.PubMedCrossRef
9.
Stavrou G, Kotzampassi K. Gut microbiome, surgical complications and probiotics. Ann Gastroenterol. 2017;30(1):45–53.PubMed
10.
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(2):e131–e41.PubMedPubMedCentralCrossRef
11.
Mokhles S, Macbeth F, Farewell V, Fiorentino F, Williams NR, Younes RN, et al. Meta-analysis of colorectal cancer follow-up after potentially curative resection. Br J Surg. 2016;103(10):1259–68.PubMedPubMedCentralCrossRef
12.
Yun JA, Huh JW, Kim HC, Park YA, Cho YB, Yun SH, et al. Local recurrence after curative resection for rectal carcinoma: the role of surgical resection. Medicine. 2016;95(27):e3942.PubMedPubMedCentralCrossRef
13.
Aoyama T, Oba K, Honda M, Sadahiro S, Hamada C, Mayanagi S, et al. Impact of postoperative complications on the colorectal cancer survival and recurrence: analyses of pooled individual patients' data from three large phase III randomized trials. Cancer medicine. 2017;6(7):1573–80.PubMedPubMedCentralCrossRef
14.
Tevis SE, Kohlnhofer BM, Stringfield S, Foley EF, Harms BA, Heise CP, et al. Postoperative complications in patients with rectal cancer are associated with delays in chemotherapy that lead to worse disease-free and overall survival. Dis Colon Rectum. 2013;56(12):1339–48.PubMedCrossRef
15.
Higgins JPTTJ, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editors. Cochrane handbook for systematic reviews of interventions. 2nd edition. Chichester (UK): John Wiley & Sons; 2019.
16.
17.
Ringel Y, Maharshak N, Ringel-Kulka T, Wolber EA, Sartor RB, Carroll IM. High throughput sequencing reveals distinct microbial populations within the mucosal and luminal niches in healthy individuals. Gut Microbes. 2015;6(3):173–81.PubMedPubMedCentralCrossRef
18.
Rahbari NN, Weitz J, Hohenberger W, Heald RJ, Moran B, Ulrich A, et al. Definition and grading of anastomotic leakage following anterior resection of the rectum: a proposal by the International Study Group of Rectal Cancer. Surgery. 2010;147(3):339–51.PubMedCrossRef
19.
organisation Wh. Global guidlines for the prevention of surgical site infection World health organisation; 2016. 184 p.
20.
Wolthuis AM, Bislenghi G, Fieuws S, de Buck van Overstraeten A, Boeckxstaens G, D'Hoore A. Incidence of prolonged postoperative ileus after colorectal surgery: a systematic review and meta-analysis. Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland. 2016;18(1):O1–9.CrossRef
21.
Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603–5.PubMedCrossRef
22.
Flanagan L, Schmid J, Ebert M, Soucek P, Kunicka T, Liska V, et al. Fusobacterium nucleatum associates with stages of colorectal neoplasia development, colorectal cancer and disease outcome. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. 2014;33(8):1381–90.CrossRef
23.
Flemer B, Herlihy M, O'Riordain M, Shanahan F, O'Toole PW. Tumour-associated and non-tumour-associated microbiota: Addendum. Gut Microbes. 2018;9(4):369–73.PubMedPubMedCentral
24.
Kosumi K, Hamada T, Koh H, Borowsky J, Bullman S, Twombly TS, et al. The amount of Bifidobacterium genus in colorectal carcinoma tissue in relation to tumor characteristics and clinical outcome. Am J Pathol. 2018;188(12):2839–52.PubMedPubMedCentralCrossRef
25.
Mima K, Nishihara R, Qian ZR, Cao Y, Sukawa Y, Nowak JA, et al. Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis. Gut. 2016;65(12):1973–80.PubMedCrossRef
26.
Wei Z, Cao S, Liu S, Yao Z, Sun T, Li Y, 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):46158–72.PubMedPubMedCentralCrossRef
27.
Yan X, Liu L, Li H, Qin H, Sun Z. Clinical significance of Fusobacterium nucleatum, epithelial-mesenchymal transition, and cancer stem cell markers in stage III/IV colorectal cancer patients. OncoTargets and therapy. 2017;10:5031–46.PubMedPubMedCentralCrossRef
28.
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):548–63.e16.PubMedPubMedCentralCrossRef
29.
van Praagh JB, de Goffau MC, Bakker IS, van Goor H, Harmsen HJM, Olinga P, et al. Mucus microbiome of anastomotic tissue during surgery has predictive value for colorectal anastomotic leakage. Ann Surg. 2019;269(5):911–6.PubMedCrossRef
30.
van Praagh JB, de Goffau MC, Bakker IS, Harmsen HJ, Olinga P, Havenga K. Intestinal microbiota and anastomotic leakage of stapled colorectal anastomoses: a pilot study. Surg Endosc. 2016;30(6):2259–65.PubMedCrossRef
31.
Riviere A, Selak M, Lantin D, Leroy F, De Vuyst L. Bifidobacteria and butyrate-producing colon bacteria: importance and strategies for their stimulation in the human gut. Front Microbiol. 2016;7:979.PubMedPubMedCentralCrossRef
32.
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(2):207–15.PubMedPubMedCentralCrossRef
33.
34.
Li YY, Ge QX, Cao J, Zhou YJ, Du YL, Shen B, et al. Association of Fusobacterium nucleatum infection with colorectal cancer in Chinese patients. World J Gastroenterol. 2016;22(11):3227–33.PubMedPubMedCentralCrossRef
35.
Purcell RV, Pearson J, Aitchison A, Dixon L, Frizelle FA, Keenan JI. Colonization with enterotoxigenic Bacteroides fragilis is associated with early-stage colorectal neoplasia. PLoS One. 2017;12(2):e0171602.PubMedPubMedCentralCrossRef
36.
Viljoen KS, Dakshinamurthy A, Goldberg P, Blackburn JM. Quantitative profiling of colorectal cancer-associated bacteria reveals associations between fusobacterium spp., enterotoxigenic Bacteroides fragilis (ETBF) and clinicopathological features of colorectal cancer. PLoS One. 2015;10(3):e0119462.PubMedPubMedCentralCrossRef
37.
Tojo R, Suarez A, Clemente MG, de los Reyes-Gavilan CG, Margolles A, Gueimonde M, et al. Intestinal microbiota in health and disease: role of bifidobacteria in gut homeostasis. World J Gastroenterol. 2014;20(41):15163–76.PubMedPubMedCentralCrossRef
38.
Borges-Canha M, Portela-Cidade JP, Dinis-Ribeiro M, Leite-Moreira AF, Pimentel-Nunes P. Role of colonic microbiota in colorectal carcinogenesis: a systematic review. Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva. 2015;107(11):659–71.
39.
Fukuda S, Toh H, Hase K, Oshima K, Nakanishi Y, Yoshimura K, et al. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature. 2011;469(7331):543–7.PubMedCrossRef
40.
Flemer B, Lynch DB, Brown JM, Jeffery IB, Ryan FJ, Claesson MJ, et al. Tumour-associated and non-tumour-associated microbiota in colorectal cancer. Gut. 2017;66(4):633–43.PubMedCrossRef
41.
Luder Ripoli F, Mohr A, Conradine Hammer S, Willenbrock S, Hewicker-Trautwein M, Hennecke S, et al. A comparison of fresh frozen vs. formalin-fixed, paraffin-embedded specimens of canine mammary tumors via branched-DNA assay. Int J Mol Sci. 2016;17:5.
42.
Gupta VK, Paul S, Dutta C. Geography, ethnicity or subsistence-specific variations in human microbiome composition and diversity. Front Microbiol. 2017;8:1162.PubMedPubMedCentralCrossRef
43.
Wiegerinck M, Hyoju SK, Mao J, Zaborin A, Adriaansens C, Salzman E, et al. Novel de novo synthesized phosphate carrier compound ABA-PEG20k-Pi20 suppresses collagenase production in Enterococcus faecalis and prevents colonic anastomotic leak in an experimental model. Br J Surg. 2018;105(10):1368–76.PubMedPubMedCentralCrossRef
44.
Wirbel J, Pyl PT, Kartal E, Zych K, Kashani A, Milanese A, et al. Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer. Nat Med. 2019;25(4):679–89.PubMedPubMedCentralCrossRef
45.
Thomas AM, Manghi P, Asnicar F, Pasolli E, Armanini F, Zolfo M, et al. Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation. Nat Med. 2019;25(4):667–78.PubMedCrossRef
46.
Yachida S, Mizutani S, Shiroma H, Shiba S, Nakajima T, Sakamoto T, et al. Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer. Nat Med. 2019;25(6):968–76.PubMedCrossRef
47.
Vo E, Massarweh NN, Chai CY, Tran Cao HS, Zamani N, Abraham S, et al. Association of the addition of oral antibiotics to mechanical bowel preparation for left colon and rectal cancer resections with reduction of surgical site infections. JAMA surgery. 2018;153(2):114–21.PubMedCrossRef
Metadata
Title
Role of the intestinal microbiome in colorectal cancer surgery outcomes
Authors
Lelde Lauka
Elisa Reitano
Maria Clotilde Carra
Federica Gaiani
Paschalis Gavriilidis
Francesco Brunetti
Gian Luigi de’Angelis
Iradj Sobhani
Nicola de’Angelis
Publication date
01-12-2019
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2019
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/s12957-019-1754-x

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