Subscribe to RSS
DOI: 10.1055/s-0043-1760718
The Influence of the Microbiome on Anastomotic Leak
Abstract
Anastomotic leak, defined by the International Study Group of Rectal Cancer as “a communication between the intra- and extraluminal compartments owing to a defect of the integrity of the intestinal wall at the anastomosis,” is one of the most devastating complications in colorectal surgery. Much work has been done to identify causes of leak; however, despite advances in surgical technique, the prevalence of anastomotic leak has remained at around 11%. The potential causative role of bacteria in the etiopathology of anastomotic leak was established in the 1950s. More recently, alterations in the colonic microbiome have been shown to affect rates of anastomotic leak. Multiple perioperative factors that alter the homeostasis of the gut microbiota community structure and function have been linked to anastomotic leak after colorectal surgery. Here, we discuss the role of diet, radiation, bowel preparation, medications including nonsteroidal anti-inflammatory drugs, morphine, and antibiotics, and specific microbial pathways that have been implicated in anastomotic leak via their effects on the microbiome.
* Contributed equally to this article.
Publication History
Article published online:
17 January 2023
© 2023. Thieme. All rights reserved.
Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA
-
References
- 1 Lauka L, Reitano E, Carra MC. et al. Role of the intestinal microbiome in colorectal cancer surgery outcomes. World J Surg Oncol 2019; 17 (01) 204
- 2 Rahbari NN, Weitz J, Hohenberger W. 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 (03) 339-351
- 3 Williamson AJ, Alverdy JC. Influence of the microbiome on anastomotic leak. Clin Colon Rectal Surg 2021; 34 (06) 439-446
- 4 Shogan BD, Carlisle EM, Alverdy JC, Umanskiy K. Do we really know why colorectal anastomoses leak?. J Gastrointest Surg 2013; 17 (09) 1698-1707
- 5 Cohn Jr I, Rives JD. Antibiotic protection of colon anastomoses. Ann Surg 1955; 141 (05) 707-717
- 6 LeVeen HH, Wapnick S, Falk G. et al. Effects of prophylactic antibiotics on colonic healing. Am J Surg 1976; 131 (01) 47-53
- 7 Schardey HM, Kamps T, Rau HG, Gatermann S, Baretton G, Schildberg FW. Bacteria: a major pathogenic factor for anastomotic insufficiency. Antimicrob Agents Chemother 1994; 38 (11) 2564-2567
- 8 Schardey HM, Joosten U, Finke U. et al. The prevention of anastomotic leakage after total gastrectomy with local decontamination. A prospective, randomized, double-blind, placebo-controlled multicenter trial. Ann Surg 1997; 225 (02) 172-180
- 9 Clarke JS, Condon RE, Bartlett JG, Gorbach SL, Nichols RL, Ochi S. Preoperative oral antibiotics reduce septic complications of colon operations: results of prospective, randomized, double-blind clinical study. Ann Surg 1977; 186 (03) 251-259
- 10 Poggio JL. Perioperative strategies to prevent surgical-site infection. Clin Colon Rectal Surg 2013; 26 (03) 168-173
- 11 Defazio J, Fleming ID, Shakhsheer B, Zaborina O, Alverdy JC. The opposing forces of the intestinal microbiome and the emerging pathobiome. Surg Clin North Am 2014; 94 (06) 1151-1161
- 12 Gershuni VM, Friedman ES. The microbiome-host interaction as a potential driver of anastomotic leak. Curr Gastroenterol Rep 2019; 21 (01) 4
- 13 Li YD, He KX, Zhu WF. Correlation between invasive microbiota in margin-surrounding mucosa and anastomotic healing in patients with colorectal cancer. World J Gastrointest Oncol 2019; 11 (09) 717-728
- 14 van Praagh JB, de Goffau MC, Bakker IS, Harmsen HJM, Olinga P, Havenga K. Intestinal microbiota and anastomotic leakage of stapled colorectal anastomoses: a pilot study. Surg Endosc 2016; 30 (06) 2259-2265
- 15 Jin X, Liu Y, Yan W. et al. Gut microbiota from nCAL patients promotes colon anastomotic healing by inducing collagen synthesis in epithelial cells. J Gastroenterol Hepatol 2022; 37 (09) 1756-1767
- 16 Liu Y, He W, Yang J, He Y, Wang Z, Li K. The effects of preoperative intestinal dysbacteriosis on postoperative recovery in colorectal cancer surgery: a prospective cohort study. BMC Gastroenterol 2021; 21 (01) 446
- 17 Wong JMW, de Souza R, Kendall CWC, Emam A, Jenkins DJA. Colonic health: fermentation and short chain fatty acids. J Clin Gastroenterol 2006; 40 (03) 235-243
- 18 Puertollano E, Kolida S, Yaqoob P. Biological significance of short-chain fatty acid metabolism by the intestinal microbiome. Curr Opin Clin Nutr Metab Care 2014; 17 (02) 139-144
- 19 Bloemen JG, Schreinemacher MH, de Bruine AP, Buurman WA, Bouvy ND, Dejong CH. Butyrate enemas improve intestinal anastomotic strength in a rat model. Dis Colon Rectum 2010; 53 (07) 1069-1075
- 20 Palmisano S, Campisciano G, Iacuzzo C. et al. Role of preoperative gut microbiota on colorectal anastomotic leakage: preliminary results. Updates Surg 2020; 72 (04) 1013-1022
- 21 Christ A, Lauterbach M, Latz E. Western diet and the immune system: an inflammatory connection. Immunity 2019; 51 (05) 794-811
- 22 Agus A, Denizot J, Thévenot J. et al. Western diet induces a shift in microbiota composition enhancing susceptibility to Adherent-Invasive E. coli infection and intestinal inflammation. Sci Rep 2016; 6 (01) 19032
- 23 Hyoju SK, Adriaansens C, Wienholts K. et al. Low-fat/high-fibre diet prehabilitation improves anastomotic healing via the microbiome: an experimental model. Br J Surg 2020; 107 (06) 743-755
- 24 Carmichael JC, Keller DS, Baldini G. et al. Clinical practice guidelines for enhanced recovery after colon and rectal surgery from the American Society of Colon and Rectal Surgeons and Society of American Gastrointestinal and Endoscopic Surgeons. Dis Colon Rectum 2017; 60 (08) 761-784
- 25 Sciuto A, Merola G, De Palma GD. et al. Predictive factors for anastomotic leakage after laparoscopic colorectal surgery. World J Gastroenterol 2018; 24 (21) 2247-2260
- 26 Pommergaard HC, Gessler B, Burcharth J, Angenete E, Haglind E, Rosenberg J. Preoperative risk factors for anastomotic leakage after resection for colorectal cancer: a systematic review and meta-analysis. Colorectal Dis 2014; 16 (09) 662-671
- 27 Liu J, Liu C, Yue J. Radiotherapy and the gut microbiome: facts and fiction. Radiat Oncol 2021; 16 (01) 9
- 28 Brook I, Walker RI, MacVittie TJ. Effect of antimicrobial therapy on bowel flora and bacterial infection in irradiated mice. Int J Radiat Biol Relat Stud Phys Chem Med 1988; 53 (05) 709-716
- 29 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
- 30 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
- 31 Pineda CE, Shelton AA, Hernandez-Boussard T, Morton JM, Welton ML. Mechanical bowel preparation in intestinal surgery: a meta-analysis and review of the literature. J Gastrointest Surg 2008; 12 (11) 2037-2044
- 32 Dahabreh IJ, Steele DW, Shah N, Trikalinos TA. Oral mechanical bowel preparation for colorectal surgery: systematic review and meta-analysis. Dis Colon Rectum 2015; 58 (07) 698-707
- 33 Cannon JA, Altom LK, Deierhoi RJ. et al. Preoperative oral antibiotics reduce surgical site infection following elective colorectal resections. Dis Colon Rectum 2012; 55 (11) 1160-1166
- 34 Morris MS, Graham LA, Chu DI, Cannon JA, Hawn MT. Oral antibiotic bowel preparation significantly reduces surgical site infection rates and readmission rates in elective colorectal surgery. Ann Surg 2015; 261 (06) 1034-1040
- 35 Scarborough JE, Mantyh CR, Sun Z, Migaly J. Combined mechanical and oral antibiotic bowel preparation reduces incisional surgical site infection and anastomotic leak rates after elective colorectal resection: an analysis of colectomy-targeted ACS NSQIP. Ann Surg 2015; 262 (02) 331-337
- 36 Koskenvuo L, Lehtonen T, Koskensalo S. et al. Mechanical and oral antibiotic bowel preparation versus no bowel preparation for elective colectomy (MOBILE): a multicentre, randomised, parallel, single-blinded trial. Lancet 2019; 394 (10201): 840-848
- 37 Rollins KE, Javanmard-Emamghissi H, Acheson AG, Lobo DN. The role of oral antibiotic preparation in elective colorectal surgery: a meta-analysis. Ann Surg 2019; 270 (01) 43-58
- 38 Nalluri-Butz H, Bobel MC, Nugent J. et al. A pilot study demonstrating the impact of surgical bowel preparation on intestinal microbiota composition following colon and rectal surgery. Sci Rep 2022; 12 (01) 10559
- 39 Gustafsson UO, Scott MJ, Hubner M. et al. Guidelines for perioperative care in elective colorectal surgery: Enhanced Recovery After Surgery (ERAS®) Society Recommendations: 2018. World J Surg 2019; 43 (03) 659-695
- 40 Agnes A, Puccioni C, D'Ugo D, Gasbarrini A, Biondi A, Persiani R. The gut microbiota and colorectal surgery outcomes: facts or hype? A narrative review. BMC Surg 2021; 21 (01) 83
- 41 Lam A, Fleischer B, Alverdy J. The biology of anastomotic healing-the unknown overwhelms the known. J Gastrointest Surg 2020; 24 (09) 2160-2166
- 42 2017 European Society of Coloproctology (ESCP) collaborating group. Association of mechanical bowel preparation with oral antibiotics and anastomotic leak following left sided colorectal resection: an international, multi-centre, prospective audit. Colorectal Dis 2018; 20 (Suppl. 06) 15-32
- 43 Wirth U, Rogers S, Haubensak K, Schopf S, von Ahnen T, Schardey HM. Local antibiotic decontamination to prevent anastomotic leakage short-term outcome in rectal cancer surgery. Int J Colorectal Dis 2018; 33 (01) 53-60
- 44 Hajjar R, Santos MM, Dagbert F, Richard CS. Current evidence on the relation between gut microbiota and intestinal anastomotic leak in colorectal surgery. Am J Surg 2019; 218 (05) 1000-1007
- 45 Jernberg C, Löfmark S, Edlund C, Jansson JK. Long-term ecological impacts of antibiotic administration on the human intestinal microbiota. ISME J 2007; 1 (01) 56-66
- 46 Gaines S, Hyoju S, Williamson AJ. et al. Infliximab does not promote the presence of collagenolytic bacteria in a mouse model of colorectal anastomosis. J Gastrointest Surg 2020; 24 (11) 2637-2642
- 47 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 (02) 386-393
- 48 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
- 49 Holte K, Andersen J, Jakobsen DH, Kehlet H. Cyclo-oxygenase 2 inhibitors and the risk of anastomotic leakage after fast-track colonic surgery. Br J Surg 2009; 96 (06) 650-654
- 50 Yauw STK, Arron M, Lomme RMLM. et al. Microbial glucuronidase inhibition reduces severity of diclofenac-induced anastomotic leak in rats. Surg Infect (Larchmt) 2018; 19 (04) 417-423
- 51 Shogan BD, Smith DP, Christley S, Gilbert JA, Zaborina O, Alverdy JC. Intestinal anastomotic injury alters spatially defined microbiome composition and function. Microbiome 2014; 2: 35
- 52 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
- 53 Hyoju SK, Klabbers RE, Aaron M. et al. Oral polyphosphate suppresses bacterial collagenase production and prevents anastomotic leak due to Serratia marcescens and Pseudomonas aeruginosa. Ann Surg 2018; 267 (06) 1112-1118
- 54 Reischl S, Wilhelm D, Friess H, Neumann PA. Innovative approaches for induction of gastrointestinal anastomotic healing: an update on experimental and clinical aspects. Langenbecks Arch Surg 2021; 406 (04) 971-980
- 55 Carlini M, Grieco M, Spoletini D. et al. Implementation of the gut microbiota prevents anastomotic leaks in laparoscopic colorectal surgery for cancer:the results of the MIRACLe study. Updates Surg 2022; 74 (04) 1253-1262