The gut microbiota and gastrointestinal surgery

Journal name:
Nature Reviews Gastroenterology & Hepatology
Volume:
14,
Pages:
43–54
Year published:
DOI:
doi:10.1038/nrgastro.2016.139
Published online

Abstract

Surgery involving the gastrointestinal tract continues to prove challenging because of the persistence of unpredictable complications such as anastomotic leakage and life-threatening infections. Removal of diseased intestinal segments results in substantial catabolic stress and might require complex reconstructive surgery to maintain the functional continuity of the intestinal tract. As gastrointestinal surgery necessarily involves a breach of an epithelial barrier colonized by microorganisms, preoperative intestinal antisepsis is used to reduce infection-related complications. The current approach to intestinal antisepsis varies widely across institutions and countries with little understanding of its mechanism of action, effect on the gut microbiota and overall efficacy. Many of the current approaches to intestinal antisepsis before gastrointestinal surgery run counter to emerging concepts of intestinal microbiota contributing to immune function and recovery from injury. Here, we review evidence outlining the role of gut microbiota in recovery from gastrointestinal surgery, particularly in the development of infections and anastomotic leak. To make surgery safer and further reduce complications, a molecular, genetic and functional understanding of the response of the gastrointestinal tract to alterations in its microbiota is needed. Methods can then be developed to preserve the health-promoting functions of the microbiota while at the same time suppressing their harmful effects.

At a glance

Figures

  1. The effect of perioperative events on the intestinal microbiota.
    Figure 1: The effect of perioperative events on the intestinal microbiota.

    The entire process of intestinal surgery, from preoperative preparation to the recovery phase has a substantial and cumulative effect on the intestinal microbiota. a | Baseline microbiota. b | Purgative cleansing eliminates bulky intestinal content and oral antibiotics reduce the luminal bacterial load, leaving behind certain strains of mucosa-associated bacteria. c | Intravenous (IV) antibiotics exert further selective pressure on bacterial composition and function. d | Surgical stress might shift bacterial phenotypes. e | The healthy recovery phase includes refaunation of commensal bacteria; however, selective pressures during microbiota elimination might fundamentally change the subsequent microbiota. MBP, mechanical bowel preparation.

  2. Host-microorganism communication.
    Figure 2: Host–microorganism communication.

    Bacteria and their human hosts communicate and sense one another through various mechanisms. The host immune system can sense bacteria through microorganism-associated molecular patterns (MAMPs) and through bacterial functions such as bile acid conjugation. Bacteria can sense the host state through secreted hormones, opioids and inflammatory signals. Microorganisms communicate among themselves through quorum sensing and the exchange of genetic material.

  3. Altering anatomy alters the physiology and microenvironment of the intestine.
    Figure 3: Altering anatomy alters the physiology and microenvironment of the intestine.

    a | Normal anatomy. b | Roux-en-Y gastric bypass and c | pancreaticoduodenectomy.

  4. Microbial pathogenesis of anastomotic leak: context-dependent virulence expression in response to cues released by surgically injured tissues.
    Figure 4: Microbial pathogenesis of anastomotic leak: context-dependent virulence expression in response to cues released by surgically injured tissues.

    The tissue response to a surgical injury has a key and contributory role in the phenotype transformation or selection of intestinal microorganisms that cause anastomotic leak. The patient undergoes surgical resection inducing physiological stress. The pro-inflammatory reaction releases host stress signals into the local intestinal environment (1). Bacteria recognize host stress signals (2). Bacteria respond to host stress by increasing their adherence capacity and increasing collagenase production (3). Bacterial collagenase breaks down collagen I and activates local tissue matrix metalloproteinase (MMP)9, which then cleaves collagen IV (3). The net result of this process is anastomotic tissue breakdown due to colonizing pathogens that have been 'cued' to express collagenase and cleave MMP9132 (4). MMP, matrix metalloproteinase.

References

  1. Merkow, R. P. et al. Underlying reasons associated with hospital readmission following surgery in the United States. JAMA 313, 483495 (2015).
  2. Clarke, J. S. et al. Preoperative oral antibiotics reduce septic complications of colon operations: results of prospective, randomized, double-blind clinical study. Ann. Surg. 186, 251259 (1977).
  3. Schubert, A. M., Sinani, H. & Schloss, P. D. Antibiotic-induced alterations of the murine gut microbiota and subsequent effects on colonization resistance against Clostridium difficile. MBio 6, e00974 (2015).
  4. Britton, R. A. & Young, V. B. Role of the intestinal microbiota in resistance to colonization by Clostridium difficile. Gastroenterology 146, 15471553 (2014).
  5. Deitch, E. A. Gut-origin sepsis: evolution of a concept. Surgeon 10, 350356 (2012).
  6. Vaishnavi, C. Translocation of gut flora and its role in sepsis. Indian J. Med. Microbiol. 31, 334342 (2013).
  7. Yu, L. C.-H. et al. Enteric dysbiosis promotes antibiotic-resistant bacterial infection: systemic dissemination of resistant and commensal bacteria through epithelial transcytosis. Am. J. Physiol. Gastrointest. Liver Physiol. 307, G824G835 (2014).
  8. Piton, G. & Capellier, G. Biomarkers of gut barrier failure in the ICU. Curr. Opin. Crit. Care 22, 152160 (2016).
  9. Gibson, M. K., Pesesky, M. W. & Dantas, G. The yin and yang of bacterial resilience in the human gut microbiota. J. Mol. Biol. 426, 38663876 (2014).
  10. Sassone-Corsi, M. & Raffatellu, M. No vacancy: how beneficial microbes cooperate with immunity to provide colonization resistance to pathogens. J. Immunol. 194, 40814087 (2015).
  11. Caballero, S. & Pamer, E. G. Microbiota-mediated inflammation and antimicrobial defense in the intestine. Annu. Rev. Immunol. 33, 227256 (2015).
  12. Kamada, N., Chen, G. Y., Inohara, N. & Núñez, G. Control of pathogens and pathobionts by the gut microbiota. Nat. Immunol. 14, 685690 (2013).
  13. Kasubuchi, M., Hasegawa, S., Hiramatsu, T., Ichimura, A. & Kimura, I. Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation. Nutrients 7, 28392849 (2015).
  14. Macfarlane, G. T. & Macfarlane, S. Bacteria, colonic fermentation, and gastrointestinal health. J. AOAC Int. 95, 5060 (2012).
  15. Chen, J. et al. Interaction between microbes and host intestinal health: modulation by dietary nutrients and gut-brain-endocrine-immune axis. Curr. Protein Pept. Sci. 16, 592603 (2015).
  16. Fan, P. et al. Metabolites of dietary protein and peptides by intestinal microbes and their impacts on gut. Curr. Protein Pept. Sci. 16, 646654 (2015).
  17. Malago, J. J. Contribution of microbiota to the intestinal physicochemical barrier. Benef. Microbes 6, 295311 (2015).
  18. Schreiber, F., Arasteh, J. M. & Lawley, T. D. Pathogen resistance mediated by IL-22 signaling at the epithelial-microbiota interface. J. Mol. Biol. 427, 36763682 (2015).
  19. Littman, D. R. & Pamer, E. G. Role of the commensal microbiota in normal and pathogenic host immune responses. Cell Host Microbe 10, 311323 (2011).
  20. Gaboriau-Routhiau, V. et al. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity 31, 677689 (2009).
  21. Mulder, I. E. et al. Restricting microbial exposure in early life negates the immune benefits associated with gut colonization in environments of high microbial diversity. PLoS ONE 6, e28279 (2011).
  22. Mulder, I. E. et al. Environmentally-acquired bacteria influence microbial diversity and natural innate immune responses at gut surfaces. BMC Biol. 7, 79 (2009).
  23. Abt, M. C. & Pamer, E. G. Commensal bacteria mediated defenses against pathogens. Curr. Opin. Immunol. 29, 1622 (2014).
  24. Buffie, C. G. & Pamer, E. G. Microbiota-mediated colonization resistance against intestinal pathogens. Nat. Rev. Immunol. 13, 790801 (2013).
  25. Gerber, G. K. The dynamic microbiome. FEBS Lett. 588, 41314139 (2014).
  26. David, L. A. et al. Host lifestyle affects human microbiota on daily timescales. Genome Biol. 15, R89 (2014).
  27. Lax, S. et al. Longitudinal analysis of microbial interaction between humans and the indoor environment. Science 345, 10481052 (2014).
  28. Joshi, V. et al. Smoking decreases structural and functional resilience in the subgingival ecosystem. J. Clin. Periodontol. 41, 10371047 (2014).
  29. Allais, L. et al. Chronic cigarette smoke exposure induces microbial and inflammatory shifts and mucin changes in the murine gut. Environ. Microbiol. 18, 13521363 (2015).
  30. Campbell, S. C. et al. The effect of diet and exercise on intestinal integrity and microbial diversity in mice. PLoS ONE 11, e0150502 (2016).
  31. Lozupone, C. A., Stombaugh, J. I., Gordon, J. I., Jansson, J. K. & Knight, R. Diversity, stability and resilience of the human gut microbiota. Nature 489, 220230 (2012).
  32. Earley, Z. M. et al. Burn injury alters the intestinal microbiome and increases gut permeability and bacterial translocation. PLoS ONE 10, e0129996 (2015).
  33. Shimizu, K. et al. Gut microbiota and environment in patients with major burns – a preliminary report. Burns 41, e28e33 (2015).
  34. Krishnan, P., Frew, Q., Green, A., Martin, R. & Dziewulski, P. Cause of death and correlation with autopsy findings in burns patients. Burns 39, 583588 (2013).
  35. Shimizu, K. et al. Altered gut flora are associated with septic complications and death in critically ill patients with systemic inflammatory response syndrome. Dig. Dis. Sci. 56, 11711177 (2011).
  36. Shogan, B. D. et al. Intestinal anastomotic injury alters spatially defined microbiome composition and function. Microbiome 2, 35 (2014).
  37. Sommovilla, J. et al. Small bowel resection induces long-term changes in the enteric microbiota of mice. J. Gastrointest. Surg. 19, 5664 (2015).
  38. Hartman, A. L. et al. Human gut microbiome adopts an alternative state following small bowel transplantation. Proc. Natl Acad. Sci. USA 106, 1718717192 (2009).
  39. Wang, F. et al. Temporal variations of the ileal microbiota in intestinal ischemia and reperfusion. Shock 39, 96103 (2013).
  40. Wang, F., Li, Q., Wang, C., Tang, C. & Li, J. Dynamic alteration of the colonic microbiota in intestinal ischemia-reperfusion injury. PLoS ONE 7, e42027 (2012).
  41. Wang, H. et al. Bifidobacteria may be beneficial to intestinal microbiota and reduction of bacterial translocation in mice following ischaemia and reperfusion injury. Br. J. Nutr. 109, 19901998 (2013).
  42. Perez-Chanona, E., Mühlbauer, M. & Jobin, C. The microbiota protects against ischemia/reperfusion-induced intestinal injury through nucleotide-binding oligomerization domain-containing protein 2 (NOD2) signaling. Am. J. Pathol. 184, 29652975 (2014).
  43. Zarrinpar, A., Chaix, A., Yooseph, S. & Panda, S. Diet and feeding pattern affect the diurnal dynamics of the gut microbiome. Cell Metab. 20, 10061017 (2014).
  44. Jalanka, J. et al. Effects of bowel cleansing on the intestinal microbiota. Gut 64, 15621568 (2015).
  45. Antonopoulos, D. A. et al. Reproducible community dynamics of the gastrointestinal microbiota following antibiotic perturbation. Infect. Immun. 77, 23672375 (2009).
  46. Ferrer, M., Martins dos Santos, V. A. P., Ott, S. J. & Moya, A. Gut microbiota disturbance during antibiotic therapy: a multi-omic approach. Gut Microbes 5, 6470 (2014).
  47. Ubeda, C. & Pamer, E. G. Antibiotics, microbiota, and immune defense. Trends Immunol. 33, 459466 (2012).
  48. Güenaga, K. F., Matos, D. & Wille-Jørgensen, P. Mechanical bowel preparation for elective colorectal surgery. Cochrane Database Syst. Rev. 9, CD001544 (2011).
  49. Nelson, R. L., Gladman, E. & Barbateskovic, M. Antimicrobial prophylaxis for colorectal surgery. Cochrane Database Syst. Rev. 5, CD001181 (2014).
  50. Kasiraj, A. C. et al. The effects of feeding and withholding food on the canine small intestinal microbiota. FEMS Microbiol. Ecol. 92, fiw085 (2016).
  51. Wu, Y., Wu, C., Zhang, X., Ou, W. & Huang, P. Clinical study of different bowel preparations on changes of gut flora in patients undergoing colorectal resection [Chinese]. Zhonghua Wei Chang Wai Ke Za Zhi 15, 574577 (2012).
  52. Smith, M. B. et al. Suppression of the human mucosal-related colonic microflora with prophylactic parenteral and/or oral antibiotics. World J. Surg. 14, 636641 (1990).
  53. Huipeng, W., Lifeng, G., Chuang, G., Jiaying, Z. & Yuankun, C. The differences in colonic mucosal microbiota between normal individual and colon cancer patients by polymerase chain reaction-denaturing gradient gel electrophoresis. J. Clin. Gastroenterol. 48, 138144 (2014).
  54. Lam, V. et al. Intestinal microbiota as novel biomarkers of prior radiation exposure. Radiat. Res. 177, 573583 (2012).
  55. Kim, Y. S., Kim, J. & Park, S.-J. High-throughput 16S rRNA gene sequencing reveals alterations of mouse intestinal microbiota after radiotherapy. Anaerobe 33, 17 (2015).
  56. Montassier, E. et al. Chemotherapy-driven dysbiosis in the intestinal microbiome. Aliment. Pharmacol. Ther. 42, 515528 (2015).
  57. Schwabe, R. F. & Jobin, C. The microbiome and cancer. Nat. Rev. Cancer 13, 800812 (2013).
  58. Tang, Y. et al. Administration of probiotic mixture DM#1 ameliorated 5-fluorouracil-induced intestinal mucositis and dysbiosis in rats. Nutrition http://dx.doi.org/10.1016/j.nut.2016.05.003 (2016).
  59. Iida, N. et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science 342, 967970 (2013).
  60. Viaud, S. et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science 342, 971976 (2013).
  61. González-Sarrías, A., Tomé-Carneiro, J., Bellesia, A., Tomás-Barberán, F. A. & Espín, J. C. The ellagic acid-derived gut microbiota metabolite, urolithin A, potentiates the anticancer effects of 5-fluorouracil chemotherapy on human colon cancer cells. Food Funct. 6, 14601469 (2015).
  62. Leslie, M. MICROBIOME. Microbes aid cancer drugs. Science 350, 614615 (2015).
  63. Touchefeu, Y. et al. Systematic review: the role of the gut microbiota in chemotherapy- or radiation-induced gastrointestinal mucositis - current evidence and potential clinical applications. Aliment. Pharmacol. Ther. 40, 409421 (2014).
  64. Gilbert, J. A. et al. Microbiome-wide association studies link dynamic microbial consortia to disease. Nature 535, 94103 (2016).
  65. Woting, A. & Blaut, M. The intestinal microbiota in metabolic disease. Nutrients 8, 202 (2016).
  66. Leung, V., Dufour, D. & Lévesque, C. M. Death and survival in Streptococcus mutans: differing outcomes of a quorum-sensing signaling peptide. Front. Microbiol. 6, 1176 (2015).
  67. Patenge, N., Fiedler, T. & Kreikemeyer, B. Common regulators of virulence in streptococci. Curr. Top. Microbiol. Immunol. 368, 111153 (2013).
  68. Jimenez, J. C. & Federle, M. J. Quorum sensing in group A Streptococcus. Front. Cell. Infect. Microbiol. 4, 127 (2014).
  69. Wu, L. et al. Recognition of host immune activation by Pseudomonas aeruginosa. Science 309, 774777 (2005).
  70. Ojima, M. et al. Metagenomic analysis reveals dynamic changes of whole gut microbiota in the acute phase of intensive care unit patients. Dig. Dis. Sci. 61, 16281634 (2016).
  71. Hayakawa, M. et al. Dramatic changes of the gut flora immediately after severe and sudden insults. Dig. Dis. Sci. 56, 23612365 (2011).
  72. Alcock, J. Dangerous disappearing act: commensal gut microbiota after acute severe insults. Dig. Dis. Sci. 56, 22122214 (2011).
  73. Chauv, S. et al. Risk of resistant organisms and Clostridium difficile with prolonged systemic antibiotic prophylaxis for central nervous system devices. Neurocrit. Care 25, 128132 (2016).
  74. Zaborin, A. et al. Membership and behavior of ultra-low-diversity pathogen communities present in the gut of humans during prolonged critical illness. mBio 5, e01361-14 (2014).
  75. Donaldson, G. P., Lee, S. M. & Mazmanian, S. K. Gut biogeography of the bacterial microbiota. Nat. Rev. Microbiol. 14, 2032 (2016).
  76. Okada, M., Bothin, C., Kanazawa, K. & Midtvedt, T. Experimental study of the influence of intestinal flora on the healing of intestinal anastomoses. Br. J. Surg. 86, 961965 (1999).
  77. Mizuta, M. et al. Perioperative supplementation with bifidobacteria improves postoperative nutritional recovery, inflammatory response, and fecal microbiota in patients undergoing colorectal surgery: a prospective, randomized clinical trial. Biosci. Microbiota Food Health 35, 7787 (2016).
  78. Okazaki, T. et al. Intestinal microbiota in pediatric surgical cases administered Bifidobacterium breve: a randomized controlled trial. J. Pediatr. Gastroenterol. Nutr. 63, 4650 (2016).
  79. Gustafsson, U. O., Oppelstrup, H., Thorell, A., Nygren, J. & Ljungqvist, O. Adherence to the ERAS protocol is associated with 5-year survival after colorectal cancer surgery: a retrospective cohort study. World J. Surg. 40, 17411747 (2016).
  80. Zhuang, C.-L., Ye, X.-Z., Zhang, X.-D., Chen, B.-C. & Yu, Z. Enhanced recovery after surgery programs versus traditional care for colorectal surgery: a meta-analysis of randomized controlled trials. Dis. Colon Rectum 56, 667678 (2013).
  81. Gustafsson, U. O. et al. Guidelines for perioperative care in elective colonic surgery: Enhanced Recovery After Surgery (ERAS®) Society recommendations. World J. Surg. 37, 259284 (2013).
  82. Tappenden, K. A. Intestinal adaptation following resection. JPEN J. Parenter. Enteral Nutr. 38, 23S31S (2014).
  83. Carswell, K. A. et al. The effect of bariatric surgery on intestinal absorption and transit time. Obes. Surg. 24, 796805 (2014).
  84. Zhang, Y.-J. et al. Impacts of gut bacteria on human health and diseases. Int. J. Mol. Sci. 16, 74937519 (2015).
  85. Patterson, E. et al. Gut microbiota, the pharmabiotics they produce and host health. Proc. Nutr. Soc. 73, 477489 (2014).
  86. Hammer, H. F. Medical complications of bariatric surgery: focus on malabsorption and dumping syndrome. Dig. Dis. 30, 182186 (2012).
  87. Heiman, M. L. & Greenway, F. L. A healthy gastrointestinal microbiome is dependent on dietary diversity. Mol. Metab. 5, 317320 (2016).
  88. Gralka, E. et al. Metabolomic fingerprint of severe obesity is dynamically affected by bariatric surgery in a procedure-dependent manner. Am. J. Clin. Nutr. 102, 13131322 (2015).
  89. Sakhaee, K., Poindexter, J. & Aguirre, C. The effects of bariatric surgery on bone and nephrolithiasis. Bone 84, 18 (2016).
  90. Gletsu-Miller, N. & Wright, B. N. Mineral malnutrition following bariatric surgery. Adv. Nutr. 4, 506517 (2013).
  91. Lagoo, J., Pappas, T. N. & Perez, A. A relic or still relevant: the narrowing role for vagotomy in the treatment of peptic ulcer disease. Am. J. Surg. 207, 120126 (2014).
  92. Seeley, R. J., Chambers, A. P. & Sandoval, D. A. The role of gut adaptation in the potent effects of multiple bariatric surgeries on obesity and diabetes. Cell Metab. 21, 369378 (2015).
  93. Osto, M. et al. Roux-en-Y gastric bypass surgery in rats alters gut microbiota profile along the intestine. Physiol. Behav. 119, 9296 (2013).
  94. Lutz, T. A. & Bueter, M. The physiology underlying Roux-en-Y gastric bypass: a status report. Am. J. Physiol. Regul. Integr. Comp. Physiol. 307, R12751291 (2014).
  95. Chakravartty, S., Tassinari, D., Salerno, A., Giorgakis, E. & Rubino, F. What is the mechanism behind weight loss maintenance with gastric bypass? Curr. Obes. Rep. 4, 262268 (2015).
  96. Liou, A. P. et al. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci. Transl Med. 5, 178ra41 (2013).
  97. Houghton, S. G., Romero, Y. & Sarr, M. G. Effect of Roux-en-Y gastric bypass in obese patients with Barrett's esophagus: attempts to eliminate duodenogastric reflux. Surg. Obes. Relat. Dis. 4, 15 (2008).
  98. Naik, R. D., Choksi, Y. A. & Vaezi, M. F. Consequences of bariatric surgery on oesophageal function in health and disease. Nat. Rev. Gastroenterol. Hepatol. 13, 111119 (2016).
  99. Csendes, A., Burgos, A. M., Smok, G., Burdiles, P. & Henriquez, A. Effect of gastric bypass on Barrett's esophagus and intestinal metaplasia of the cardia in patients with morbid obesity. J. Gastrointest. Surg. 10, 259264 (2006).
  100. Amir, I., Konikoff, F. M., Oppenheim, M., Gophna, U. & Half, E. E. Gastric microbiota is altered in oesophagitis and Barrett's oesophagus and further modified by proton pump inhibitors. Environ. Microbiol. 16, 29052914 (2014).
  101. Yang, L., Chaudhary, N., Baghdadi, J. & Pei, Z. Microbiome in reflux disorders and esophageal adenocarcinoma. Cancer J. 20, 207210 (2014).
  102. Snider, E. J., Freedberg, D. E. & Abrams, J. A. Potential role of the microbiome in Barrett's esophagus and esophageal adenocarcinoma. Dig. Dis. Sci. 61, 22172225 (2016).
  103. Baghdadi, J., Chaudhary, N., Pei, Z. & Yang, L. Microbiome, innate immunity, and esophageal adenocarcinoma. Clin. Lab. Med. 34, 721732 (2014).
  104. Di Pilato, V. et al. The esophageal microbiota in health and disease. Ann. NY Acad. Sci. http://dx.doi.org/10.1111/nyas.13127 (2016).
  105. Neto, A. G., Whitaker, A. & Pei, Z. Microbiome and potential targets for chemoprevention of esophageal adenocarcinoma. Semin. Oncol. 43, 8696 (2016).
  106. Jones, M. L., Martoni, C. J., Ganopolsky, J. G., Labbé, A. & Prakash, S. The human microbiome and bile acid metabolism: dysbiosis, dysmetabolism, disease and intervention. Expert Opin. Biol. Ther. 14, 467482 (2014).
  107. Miyachi, T. et al. Biliopancreatic limb plays an important role in metabolic improvement after duodenal-jejunal bypass in a rat model of diabetes. Surgery http://dx.doi.org/10.1016/j.surg.2015.11.027 (2016).
  108. Everard, A. et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc. Natl Acad. Sci. USA 110, 90669071 (2013).
  109. Flynn, C. R. et al. Bile diversion to the distal small intestine has comparable metabolic benefits to bariatric surgery. Nat. Commun. 6, 7715 (2015).
  110. Billeter, A. T. et al. Risk of malnutrition, trace metal, and vitamin deficiency post Roux-en-Y gastric bypass — a prospective study of 20 patients with BMI <35 kg/m2. Obes. Surg. 25, 21252134 (2015).
  111. Bland, C. M. et al. Long-term pharmacotherapy considerations in the bariatric surgery patient. Am. J. Health-Syst. Pharm. 73, 12301242 (2016).
  112. Distrutti, E., Monaldi, L., Ricci, P. & Fiorucci, S. Gut microbiota role in irritable bowel syndrome: new therapeutic strategies. World J. Gastroenterol. 22, 22192241 (2016).
  113. Husebye, E., Hellström, P. M. & Midtvedt, T. Intestinal microflora stimulates myoelectric activity of rat small intestine by promoting cyclic initiation and aboral propagation of migrating myoelectric complex. Dig. Dis. Sci. 39, 946956 (1994).
  114. Tan, C. K. et al. Pre-surgical administration of microbial cell preparation in colorectal cancer patients: a randomized controlled trial. World J. Surg. http://dx.doi.org/10.1007/s00268-016-3499-9 (2016).
  115. Sjöström, L. et al. Effects of bariatric surgery on cancer incidence in obese patients in Sweden (Swedish Obese Subjects Study): a prospective, controlled intervention trial. Lancet Oncol. 10, 653662 (2009).
  116. Maestro, A., Rigla, M. & Caixàs, A. Does bariatric surgery reduce cancer risk? A review of the literature. Endocrinol. Nutr. 62, 138143 (2015).
  117. Derogar, M. et al. Increased risk of colorectal cancer after obesity surgery. Ann. Surg. 258, 983988 (2013).
  118. Sweeney, T. E. & Morton, J. M. Metabolic surgery: action via hormonal milieu changes, changes in bile acids or gut microbiota? A summary of the literature. Best Pract. Res. Clin. Gastroenterol. 28, 727740 (2014).
  119. Penney, N. C., Kinross, J., Newton, R. C. & Purkayastha, S. The role of bile acids in reducing the metabolic complications of obesity after bariatric surgery: a systematic review. Int. J. Obes. 39, 15651574 (2015).
  120. Kant, P. et al. Mucosal biomarkers of colorectal cancer risk do not increase at 6 months following sleeve gastrectomy, unlike gastric bypass. Obesity (Silver Spring) 22, 202210 (2014).
  121. Sheflin, A. M., Whitney, A. K. & Weir, T. L. Cancer-promoting effects of microbial dysbiosis. Curr. Oncol. Rep. 16, 406 (2014).
  122. Vogtmann, E. & Goedert, J. J. Epidemiologic studies of the human microbiome and cancer. Br. J. Cancer 114, 237242 (2016).
  123. Shogan, B. D., Carlisle, E. M., Alverdy, J. C. & Umanskiy, K. Do we really know why colorectal anastomoses leak? J. Gastrointest. Surg. 17, 16981707 (2013).
  124. Shogan, B. D. et al. Proceedings of the first international summit on intestinal anastomotic leak, Chicago, Illinois, October 4–5, 2012. Surg. Infect. 15, 479489 (2014).
  125. Caulfield, H. & Hyman, N. H. Anastomotic leak after low anterior resection: a spectrum of clinical entities. JAMA Surg. 148, 177182 (2013).
  126. Degett, T. H., Andersen, H. S. & Gögenur, I. Indocyanine green fluorescence angiography for intraoperative assessment of gastrointestinal anastomotic perfusion: a systematic review of clinical trials. Langenbecks Arch. Surg. http://dx.doi.org/10.1007/s00423-016-1400-9 (2016).
  127. Cohn, I. & Rives, J. D. Antibiotic protection of colon anastomoses. Ann. Surg. 141, 707717 (1955).
  128. Fry, D. E. Antimicrobial bowel preparation for elective colon surgery. Surg. Infect. 17, 269274 (2016).
  129. Schardey, H. M. et al. Bacteria: a major pathogenic factor for anastomotic insufficiency. Antimicrob. Agents Chemother. 38, 25642567 (1994).
  130. Olivas, A. D. et al. Intestinal tissues induce an SNP mutation in Pseudomonas aeruginosa that enhances its virulence: possible role in anastomotic leak. PLoS ONE 7, e44326 (2012).
  131. Seal, J. B., Morowitz, M., Zaborina, O., An, G. & Alverdy, J. C. The molecular Koch's postulates and surgical infection: a view forward. Surgery 147, 757765 (2010).
  132. Shogan, B. D. et al. Collagen degradation and MMP9 activation by Enterococcus faecalis contribute to intestinal anastomotic leak. Sci. Transl Med. 7, 286ra68 (2015).
  133. Siegel, R., DeSantis, C. & Jemal, A. Colorectal cancer statistics, 2014. Cancer J. Clin. 64, 104117 (2014).
  134. Wiegering, A. et al. Improved survival of patients with colon cancer detected by screening colonoscopy. Int. J. Colorectal Dis. http://dx.doi.org/10.1007/s00384-015-2501-6 (2016).
  135. Rex, D. K. Optimal bowel preparation—a practical guide for clinicians. Nat. Rev. Gastroenterol. Hepatol. 11, 419425 (2014).
  136. O'Brien, C. L., Allison, G. E., Grimpen, F. & Pavli, P. Impact of colonoscopy bowel preparation on intestinal microbiota. PLoS ONE 8, e62815 (2013).
  137. Francino, M. P. Antibiotics and the human gut microbiome: dysbioses and accumulation of resistances. Front. Microbiol. 6, 1543 (2016).
  138. Becattini, S., Taur, Y. & Pamer, E. G. Antibiotic-induced changes in the intestinal microbiota and disease. Trends Mol. Med. 22, 458478 (2016).
  139. Woodard, G. A. et al. Probiotics improve outcomes after Roux-en-Y gastric bypass surgery: a prospective randomized trial. J. Gastrointest. Surg. 13, 11981204 (2009).
  140. Canales, B. K. & Gonzalez, R. D. Kidney stone risk following Roux-en-Y gastric bypass surgery. Transl Androl. Urol. 3, 242249 (2014).
  141. Chen, J.-C., Lee, W.-J., Tsou, J.-J., Liu, T.-P. & Tsai, P.-L. Effect of probiotics on postoperative quality of gastric bypass surgeries: a prospective randomized trial. Surg. Obes. Relat. Dis. 12, 5761 (2016).
  142. Liu, Z.-H. et al. The effects of perioperative probiotic treatment on serum zonulin concentration and subsequent postoperative infectious complications after colorectal cancer surgery: a double-center and double-blind randomized clinical trial. Am. J. Clin. Nutr. 97, 117126 (2013).
  143. Theodoropoulos, G. E. et al. Synbiotics and gastrointestinal function-related quality of life after elective colorectal cancer resection. Ann. Gastroenterol. 29, 5662 (2016).
  144. Kotzampassi, K. et al. A four-probiotics regimen reduces postoperative complications after colorectal surgery: a randomized, double-blind, placebo-controlled study. World J. Surg. 39, 27762783 (2015).
  145. Kiran, R. P., Murray, A. C. A., Chiuzan, C., Estrada, D. & Forde, K. Combined preoperative mechanical bowel preparation with oral antibiotics significantly reduces surgical site infection, anastomotic leak, and ileus after colorectal surgery. Ann. Surg. 262, 416425 (2015).
  146. Sadahiro, S. et al. Comparison between oral antibiotics and probiotics as bowel preparation for elective colon cancer surgery to prevent infection: prospective randomized trial. Surgery 155, 493503 (2014).
  147. Morris, M. S., Graham, L. A., Chu, D. I., Cannon, J. A. & Hawn, M. T. Oral antibiotic bowel preparation significantly reduces surgical site infection rates and readmission rates in elective colorectal surgery. Ann. Surg. 261, 10341040 (2015).
  148. Scarborough, J. E., Mantyh, C. R., 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. 262, 331337 (2015).
  149. Jung, B. et al. Mechanical bowel preparation does not affect the intramucosal bacterial colony count. Int. J. Colorectal Dis. 25, 439442 (2010).
  150. Bucher, P., Gervaz, P., Egger, J.-F., Soravia, C. & Morel, P. Morphologic alterations associated with mechanical bowel preparation before elective colorectal surgery: a randomized trial. Dis. Colon Rectum 49, 109112 (2006).
  151. Valuckaite, V. et al. High molecular weight polyethylene glycol (PEG 15–20) maintains mucosal microbial barrier function during intestinal graft preservation. J. Surg. Res. 183, 869875 (2013).
  152. Zaborin, A. et al. Phosphate-containing polyethylene glycol polymers prevent lethal sepsis by multidrug-resistant pathogens. Antimicrob. Agents Chemother. 58, 966977 (2014).

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Affiliations

  1. MC-6040, Department of Surgery, University of Chicago Medicine, 5841 South Maryland Avenue, Chicago, Illinois 60637, USA.

    • Kristina Guyton
  2. MC-6090, Department of Surgery, University of Chicago Medicine, 5841 South Maryland Avenue, Chicago, Illinois 60637, USA.

    • John C. Alverdy

Contributions

Both authors contributed equally to all aspects of this manuscript.

Competing interests statement

The authors declare no competing interests.

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  • Kristina Guyton

    Kristina Guyton is a general surgery resident at the University of Chicago Hospitals, USA, and a research fellow in the laboratory of Dr John Alverdy. She completed her undergraduate and medical education at the University of Chicago, USA. Her research focuses on understanding the collagen degradation capacity of enteric bacteria and the part it plays in postsurgical complications and wound healing.

  • John C. Alverdy

    John Alverdy is the Sarah and Harold Lincoln Thompson Professor of Surgery and Executive Vice Chair of the University of Chicago Department of Surgery, USA. He has been the primary investigator for the past 15 years of a NIH-funded basic science laboratory at the University of Chicago, USA, focused on host–pathogen interactions in the gut and the role of the microbiota on inflammation, sepsis, postoperative complications and wound healing.

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