The Microbiome-Host Interaction as a Potential Driver of Anastomotic Leak

  • Victoria M. GershuniEmail author
  • Elliot S. Friedman
Nutrition and Obesity (S McClave, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Nutrition and Obesity


Purpose of Review

The goal of this paper is to review current literature on the gut microbiome within the context of host response to surgery and subsequent risk of developing complications, particularly anastomotic leak. We provide background on the relationship between host and gut microbiota with description of the role of the intestinal mucus layer as an important regulator of host health.

Recent Findings

Despite improvements in surgical technique and adherence to the tenets of creating a tension-free anastomosis with adequate blood flow, the surgical community has been unable to decrease rates of anastomotic leak using the current paradigm. Rather than adhere to empirical strategies of decontamination, it is imperative to focus on the interaction between the human host and the gut microbiota that live within us. The gut microbiome has been found to play a potential role in development of post-operative complications, including but not limited to anastomotic leak. Evidence suggests that peri-operative interventions may have a role in instigating or mitigating the impact of the gut microbiota via disruption of the protective mucus layer, use of multiple medications, and activation of virulence factors.


The microbiome plays a potential role in the development of surgical complications and can be modulated by peri-operative interventions. As such, further research into this relationship is urgently needed.


Microbiome Microbiota Anastomotic leak Anastomosis Surgical site infection Colorectal surgery Gastrointestinal surgery General surgery Mechanical bowel prep 


Compliance with Ethical Standards

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Paun BC, Cassie S, MacLean AR, et al. Postoperative complications following surgery for rectal cancer. Ann Surg. 2010;251:807–18.PubMedGoogle Scholar
  2. 2.
    Shogan BD, Carlisle EM, Alverdy JC, Umanskiy K. Do we really know why colorectal anastomoses leak? J Gastrointest Surg. 2013;17:1698–707.PubMedGoogle Scholar
  3. 3.
    Hyman N, Manchester TL, Osler T, Burns B, Cataldo PA. Anastomotic leaks after intestinal anastomosis: it’s later than you think. Ann Surg. 2007;245:254–8.PubMedPubMedCentralGoogle Scholar
  4. 4.
    McArdle CS, McMillan DC, Hole DJ. Impact of anastomotic leakage on long-term survival of patients undergoing curative resection for colorectal cancer. Br J Surg. 2005;92:1150–4.PubMedGoogle Scholar
  5. 5.
    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:e131–41.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Snijders HS, Wouters MW, van Leersum NJ, et al. Meta-analysis of the risk for anastomotic leakage, the postoperative mortality caused by leakage in relation to the overall postoperative mortality. Eur J Surg Oncol. 2012;38:1013–9.PubMedGoogle Scholar
  7. 7.
    Goodman AL, Kallstrom G, Faith JJ, Reyes A, Moore A, Dantas G, et al. Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic mice. Proc Natl Acad Sci U S A. 2011;108:6252–7.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Browne HP, Forster SC, Anonye BO, Kumar N, Neville BA, Stares MD, et al. Culturing of ‘unculturable’ human microbiota reveals novel taxa and extensive sporulation. Nature. 2016;533:543–6.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Ni J, Shen T-CD, Chen EZ, Bittinger K, Bailey A, Roggiani M, et al. A role for bacterial urease in gut dysbiosis and Crohn’s disease. Sci Transl Med. 2017;9:eaah6888.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Lagier JC, Dubourg G, Million M, et al. Culturing the human microbiota and culturomics. Nat Rev Microbiol. 2018.Google Scholar
  11. 11.
    Guyton K, Alverdy JC. The gut microbiota and gastrointestinal surgery. Nat Rev Gastroenterol Hepatol. 2017;14:43–54.PubMedGoogle Scholar
  12. 12.
    Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, et al. Diversity of the human intestinal microbial flora. Science. 2005;308:1635–8.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Lagier JC, Khelaifia S, Alou MT, Ndongo S, Dione N, Hugon P, et al. Culture of previously uncultured members of the human gut microbiota by culturomics. Nat Microbiol. 2016;1:16203.PubMedGoogle Scholar
  14. 14.
    • Human Microbiome Project C. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486:207–14 Seminal work highlighting the structure and function of microbial communities at multiple body sites in a large healthy cohort. Google Scholar
  15. 15.
    Wu GD, Compher C, Chen EZ, et al. Comparative metabolomics in vegans and omnivores reveal constraints on diet-dependent gut microbiota metabolite production. Gut. 2014.Google Scholar
  16. 16.
    Bushman FD, Lewis JD, Wu GD. Diet, gut enterotypes and health: is there a link? Nestle Nutr Inst Workshop Ser. 2013;77:65–73.PubMedGoogle Scholar
  17. 17.
    • Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011;334:105–8 This study links long-term dietary patterns with distinct gut microbial community structure and shows the resiliency of these communities to short-term dietary interventions. PubMedPubMedCentralGoogle Scholar
  18. 18.
    Goodrich JK, Waters JL, Poole AC, Sutter JL, Koren O, Blekhman R, et al. Human genetics shape the gut microbiome. Cell. 2014;159:789–99.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464:59–65.PubMedPubMedCentralGoogle Scholar
  20. 20.
    McDermott AJ, Huffnagle GB. The microbiome and regulation of mucosal immunity. Immunology. 2014;142:24–31.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Singh RK, Chang HW, Yan D, Lee KM, Ucmak D, Wong K, et al. Influence of diet on the gut microbiome and implications for human health. J Transl Med. 2017;15:73.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI. Human nutrition, the gut microbiome and the immune system. Nature. 2011;474:327–36.PubMedPubMedCentralGoogle Scholar
  23. 23.
    El Aidy S, van den Bogert B, Kleerebezem M. The small intestine microbiota, nutritional modulation and relevance for health. Curr Opin Biotechnol. 2015;32:14–20.PubMedGoogle Scholar
  24. 24.
    Zoetendal EG, Raes J, van den Bogert B, Arumugam M, Booijink CCGM, Troost FJ, et al. The human small intestinal microbiota is driven by rapid uptake and conversion of simple carbohydrates. ISME J. 2012;6:1415–26.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Sender R, Fuchs S, Milo R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol. 2016;14:e1002533.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Ley RE, Peterson DA, Gordon JI. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell. 2006;124:837–48.PubMedGoogle Scholar
  27. 27.
    van den Bogert B, Erkus O, Boekhorst J, de Goffau M, Smid EJ, Zoetendal EG, et al. Diversity of human small intestinal Streptococcus and Veillonella populations. FEMS Microbiol Ecol. 2013;85:376–88.PubMedGoogle Scholar
  28. 28.
    Van den Bogert B, Boekhorst J, Herrmann R, et al. Comparative genomics analysis of Streptococcus isolates from the human small intestine reveals their adaptation to a highly dynamic ecosystem. PLoS One. 2013;8:e83418.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Moran C, Sheehan D, Shanahan F. The small bowel microbiota. Curr Opin Gastroenterol. 2015;31:130–6.PubMedGoogle Scholar
  30. 30.
    Li H, Limenitakis JP, Fuhrer T, Geuking MB, Lawson MA, Wyss M, et al. The outer mucus layer hosts a distinct intestinal microbial niche. Nat Commun. 2015;6:8292.PubMedPubMedCentralGoogle Scholar
  31. 31.
    Roux A, Payne SM, Gilmore MS. Microbial telesensing: probing the environment for friends, foes, and food. Cell Host Microbe. 2009;6:115–24.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Venkataraman A, Rosenbaum MA, Werner JJ, Winans SC, Angenent LT. Metabolite transfer with the fermentation product 2,3-butanediol enhances virulence by Pseudomonas aeruginosa. ISME J. 2014;8:1210–20.PubMedPubMedCentralGoogle Scholar
  33. 33.
    Shi N, Li N, Duan X, Niu H. Interaction between the gut microbiome and mucosal immune system. Mil Med Res. 2017;4:14.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. Diversity, stability and resilience of the human gut microbiota. Nature. 2012;489:220–30.PubMedPubMedCentralGoogle Scholar
  35. 35.
    • Sommovilla J, Zhou Y, Sun RC, Choi PM, Diaz-Miron J, Shaikh N, et al. Small bowel resection induces long-term changes in the enteric microbiota of mice. J Gastrointest Surg. 2015;19:56–64 discussion 64. This study shows that bowel resection leads to a significant and resilient alteration in the ileal microbiota.PubMedGoogle Scholar
  36. 36.
    Gibson MK, Pesesky MW, Dantas G. The yin and yang of bacterial resilience in the human gut microbiota. J Mol Biol. 2014;426:3866–76.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Bosmans JW, Jongen AC, Birchenough GM, et al. Functional mucous layer and healing of proximal colonic anastomoses in an experimental model. Br J Surg. 2017;104:619–30.PubMedGoogle Scholar
  38. 38.
    Johansson ME, Sjovall H, Hansson GC. The gastrointestinal mucus system in health and disease. Nat Rev Gastroenterol Hepatol. 2013;10:352–61.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Johansson ME, Phillipson M, Petersson J, et al. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc Natl Acad Sci U S A. 2008;105:15064–9.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Grootjans J, Hundscheid IH, Lenaerts K, et al. Ischaemia-induced mucus barrier loss and bacterial penetration are rapidly counteracted by increased goblet cell secretory activity in human and rat colon. Gut. 2013;62:250–8.PubMedGoogle Scholar
  41. 41.
    Barcelo A, Claustre J, Moro F, Chayvialle JA, Cuber JC, Plaisancié P. Mucin secretion is modulated by luminal factors in the isolated vascularly perfused rat colon. Gut. 2000;46:218–24.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Jakobsson HE, Rodriguez-Pineiro AM, Schutte A, Ermund A, Boysen P, Bemark M, et al. The composition of the gut microbiota shapes the colon mucus barrier. EMBO Rep. 2015;16:164–77.PubMedGoogle Scholar
  43. 43.
    Brownlee IA, Havler ME, Dettmar PW, Allen A, Pearson JP. Colonic mucus: secretion and turnover in relation to dietary fibre intake. Proc Nutr Soc. 2003;62:245–9.PubMedGoogle Scholar
  44. 44.
    Chassaing B, Gewirtz AT. Gut microbiota, low-grade inflammation, and metabolic syndrome. Toxicol Pathol. 2014;42:49–53.PubMedGoogle Scholar
  45. 45.
    Chassaing B, Koren O, Goodrich JK, Poole AC, Srinivasan S, Ley RE, et al. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature. 2015;519:92–6.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Png CW, Linden SK, Gilshenan KS, et al. Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria. Am J Gastroenterol. 2010;105:2420–8.PubMedGoogle Scholar
  47. 47.
    Hoskins LC, Boulding ET. Mucin degradation in human colon ecosystems. Evidence for the existence and role of bacterial subpopulations producing glycosidases as extracellular enzymes. J Clin Invest. 1981;67:163–72.PubMedPubMedCentralGoogle Scholar
  48. 48.
    Albenberg L, Esipova TV, Judge CP, Bittinger K, Chen J, Laughlin A, et al. Correlation between intraluminal oxygen gradient and radial partitioning of intestinal microbiota. Gastroenterology. 2014;147:1055–63 e8.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Friedman ES, Bittinger K, Esipova TV, Hou L, Chau L, Jiang J, et al. Microbes vs. chemistry in the origin of the anaerobic gut lumen. Proc Natl Acad Sci U S A. 2018;115:4170–5.PubMedPubMedCentralGoogle Scholar
  50. 50.
    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;6:173–81.PubMedPubMedCentralGoogle Scholar
  51. 51.
    Jalanka J, Salonen A, Salojarvi J, et al. Effects of bowel cleansing on the intestinal microbiota. Gut. 2015;64:1562–8.PubMedGoogle Scholar
  52. 52.
    Ferrer M, Martins dos Santos VA, Ott SJ, et al. Gut microbiota disturbance during antibiotic therapy: a multi-omic approach. Gut Microbes. 2014;5:64–70.PubMedGoogle Scholar
  53. 53.
    Alverdy J, Zaborina O, Wu L. The impact of stress and nutrition on bacterial-host interactions at the intestinal epithelial surface. Curr Opin Clin Nutr Metab Care. 2005;8:205–9.PubMedGoogle Scholar
  54. 54.
    •• Shogan BD, Belogortseva N, Luong PM, Zaborin A, Lax S, Bethel C, et al. Collagen degradation and MMP9 activation by Enterococcus faecalis contribute to intestinal anastomotic leak. Sci Transl Med. 2015;7:286ra68 This study demonstrates that Enterococcus faecalis contributes to the pathogenesis of anastomotic leak in an animal model; additionally, the authors show that the anastomotic tissues of human subjects undergoing colon surgery are colonized with E. faecalis . PubMedPubMedCentralGoogle Scholar
  55. 55.
    Krezalek MA, Skowron KB, Guyton KL, Shakhsheer B, Hyoju S, Alverdy JC. The intestinal microbiome and surgical disease. Curr Probl Surg. 2016;53:257–93.PubMedPubMedCentralGoogle Scholar
  56. 56.
    Lyte M. The effect of stress on microbial growth. Anim Health Res Rev. 2014;15:172–4.PubMedGoogle Scholar
  57. 57.
    Becattini S, Taur Y, Pamer EG. Antibiotic-induced changes in the intestinal microbiota and disease. Trends Mol Med. 2016;22:458–78.PubMedPubMedCentralGoogle Scholar
  58. 58.
    Francino MP. Antibiotics and the human gut microbiome: dysbioses and accumulation of resistances. Front Microbiol. 2015;6:1543.PubMedGoogle Scholar
  59. 59.
    Jernberg C, Lofmark S, Edlund C, et al. Long-term ecological impacts of antibiotic administration on the human intestinal microbiota. ISME J. 2007;1:56–66.PubMedGoogle Scholar
  60. 60.
    Aad G, Abbott B, Abdallah J, et al. Search for new particles in two-jet final states in 7 TeV proton-proton collisions with the ATLAS detector at the LHC. Phys Rev Lett. 2010;105:161801.PubMedGoogle Scholar
  61. 61.
    Stavrou G, Kotzampassi K. Gut microbiome, surgical complications and probiotics. Ann Gastroenterol. 2017;30:45–53.PubMedGoogle Scholar
  62. 62.
    Bachmann R, Leonard D, Delzenne N, Kartheuser A, Cani PD. Novel insight into the role of microbiota in colorectal surgery. Gut. 2017;66:738–49.PubMedGoogle Scholar
  63. 63.
    Rex DK. Optimal bowel preparation--a practical guide for clinicians. Nat Rev Gastroenterol Hepatol. 2014;11:419–25.PubMedGoogle Scholar
  64. 64.
    Jung B, Matthiessen P, Smedh K, Nilsson E, Ransjö U, Påhlman L. Mechanical bowel preparation does not affect the intramucosal bacterial colony count. Int J Color Dis. 2010;25:439–42.Google Scholar
  65. 65.
    Harrell L, Wang Y, Antonopoulos D, Young V, Lichtenstein L, Huang Y, et al. Standard colonic lavage alters the natural state of mucosal-associated microbiota in the human colon. PLoS One. 2012;7:e32545.PubMedPubMedCentralGoogle Scholar
  66. 66.
    •• Johansson ME, Gustafsson JK, Holmen-Larsson J, et al. Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis. Gut. 2014;63:281–91 Demonstration of the breakdown of the mucosal barrier and translocation of bacteria in mice and humans with ulcerative colitis. PubMedGoogle Scholar
  67. 67.
    Gayer CP, Basson MD. The effects of mechanical forces on intestinal physiology and pathology. Cell Signal. 2009;21:1237–44.PubMedPubMedCentralGoogle Scholar
  68. 68.
    Dahabreh IJ, Steele DW, Shah N, Trikalinos TA. Oral mechanical bowel preparation for colorectal surgery: systematic review and meta-analysis. Dis Colon Rectum. 2015;58:698–707.PubMedGoogle Scholar
  69. 69.
    • Chen M, Song X, Chen LZ, Lin ZD, Zhang XL. Comparing mechanical bowel preparation with both oral and systemic antibiotics versus mechanical bowel preparation and systemic antibiotics alone for the prevention of surgical site infection after elective colorectal surgery: a meta-analysis of randomized controlled clinical trials. Dis Colon Rectum. 2016;59:70–8 Summary of relevant literature from RCTs on use of antibiotics with and without mechanical bowel preparation and highlights the difference in effect based on route of administration. PubMedGoogle Scholar
  70. 70.
    Jung B, Pahlman L, Nystrom PO, et al. Multicentre randomized clinical trial of mechanical bowel preparation in elective colonic resection. Br J Surg. 2007;94:689–95.PubMedGoogle Scholar
  71. 71.
    Contant CM, Hop WC, van’t Sant HP, et al. Mechanical bowel preparation for elective colorectal surgery: a multicentre randomised trial. Lancet. 2007;370:2112–7.PubMedGoogle Scholar
  72. 72.
    Guenaga KF, Matos D, Wille-Jorgensen P. Mechanical bowel preparation for elective colorectal surgery. Cochrane Database Syst Rev. 2011:CD001544.Google Scholar
  73. 73.
    Cannon JA, Altom LK, Deierhoi RJ, Morris M, Richman JS, Vick CC, et al. Preoperative oral antibiotics reduce surgical site infection following elective colorectal resections. Dis Colon Rectum. 2012;55:1160–6.PubMedGoogle Scholar
  74. 74.
    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;261:1034–40.PubMedGoogle Scholar
  75. 75.
    Wang F, Li Q, Wang C, Tang C, Li J. Dynamic alteration of the colonic microbiota in intestinal ischemia-reperfusion injury. PLoS One. 2012;7:e42027.PubMedPubMedCentralGoogle Scholar
  76. 76.
    Cohn I Jr, Rives JD. Antibiotic protection of colon anastomoses. Ann Surg. 1955;141:707–17.PubMedPubMedCentralGoogle Scholar
  77. 77.
    Cohen SR, Cornell CN, Collins MH, Sell JE, Blanc WA, Altman RP. Healing of ischemic colonic anastomoses in the rat: role of antibiotic preparation. Surgery. 1985;97:443–6.PubMedGoogle Scholar
  78. 78.
    Schardey HM, Kamps T, Rau HG, Gatermann S, Baretton G, Schildberg FW. Bacteria: a major pathogenic factor for anastomotic insufficiency. Antimicrob Agents Chemother. 1994;38:2564–7.PubMedPubMedCentralGoogle Scholar
  79. 79.
    • 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 Highlights the impact of surgical injury on microbiota structure and function as it relates to development of surgical complications. PubMedPubMedCentralGoogle Scholar
  80. 80.
    Seal JB, Morowitz M, Zaborina O, An G, Alverdy JC. The molecular Koch’s postulates and surgical infection: a view forward. Surgery. 2010;147:757–65.PubMedGoogle Scholar
  81. 81.
    Alverdy JC, Chang EB. The re-emerging role of the intestinal microflora in critical illness and inflammation: why the gut hypothesis of sepsis syndrome will not go away. J Leukoc Biol. 2008;83:461–6.PubMedGoogle Scholar
  82. 82.
    Fink D, Romanowski K, Valuckaite V, et al. Pseudomonas aeruginosa potentiates the lethal effect of intestinal ischemia-reperfusion injury: the role of in vivo virulence activation. J Trauma. 2011;71:1575–82.PubMedPubMedCentralGoogle Scholar
  83. 83.
    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. 2004;173:4137–46.PubMedGoogle Scholar
  84. 84.
    Ferraro FJ, Rush BF Jr, Simonian GT, Bruce CJ, Murphy TF, Hsieh JT, et al. A comparison of survival at different degrees of hemorrhagic shock in germ-free and germ-bearing rats. Shock. 1995;4:117–20.PubMedGoogle Scholar
  85. 85.
    Babrowski T, Holbrook C, Moss J, Gottlieb L, Valuckaite V, Zaborin A, 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;255:386–93.PubMedPubMedCentralGoogle Scholar
  86. 86.
    Olivas AD, Shogan BD, Valuckaite V, Zaborin A, Belogortseva N, Musch M, et al. Intestinal tissues induce an SNP mutation in Pseudomonas aeruginosa that enhances its virulence: possible role in anastomotic leak. PLoS One. 2012;7:e44326.PubMedPubMedCentralGoogle Scholar
  87. 87.
    •• Alverdy JC, Hyoju SK, Weigerinck M, Gilbert JA. The gut microbiome and the mechanism of surgical infection. Br J Surg. 2017;104:e14–23 Detailed review of the potential mechanisms and relationships between the microbiome as it pertains to the development of surgical complications. PubMedGoogle Scholar
  88. 88.
    Alverdy JC, Hyman N, Gilbert J, Luo JN, Krezalek M. Preparing the bowel for surgery: learning from the past and planning for the future. J Am Coll Surg. 2017;225:324–32.PubMedPubMedCentralGoogle Scholar
  89. 89.
    Lewis JD, Chen EZ, Baldassano RN, Otley AR, Griffiths AM, Lee D, et al. Inflammation, antibiotics, and diet as environmental stressors of the gut microbiome in pediatric Crohn’s disease. Cell Host Microbe. 2015;18:489–500.PubMedPubMedCentralGoogle Scholar
  90. 90.
    Lambert JE, Parnell JA, Eksteen B, Raman M, Bomhof MR, Rioux KP, et al. Gut microbiota manipulation with prebiotics in patients with non-alcoholic fatty liver disease: a randomized controlled trial protocol. BMC Gastroenterol. 2015;15:169.PubMedPubMedCentralGoogle Scholar
  91. 91.
    Panigrahi P, Parida S, Nanda NC, Satpathy R, Pradhan L, Chandel DS, et al. A randomized synbiotic trial to prevent sepsis among infants in rural India. Nature. 2017;548:407–12.PubMedGoogle Scholar
  92. 92.
    Albenberg LG, Lewis JD, Wu GD. Food and the gut microbiota in inflammatory bowel diseases: a critical connection. Curr Opin Gastroenterol. 2012;28:314–20.PubMedGoogle Scholar
  93. 93.
    Gerasimidis K, Bertz M, Hanske L, Junick J, Biskou O, Aguilera M, et al. Decline in presumptively protective gut bacterial species and metabolites are paradoxically associated with disease improvement in pediatric Crohn’s disease during enteral nutrition. Inflamm Bowel Dis. 2014;20:861–71.PubMedGoogle Scholar
  94. 94.
    Kaakoush NO, Day AS, Leach ST, Lemberg DA, Nielsen S, Mitchell HM. Effect of exclusive enteral nutrition on the microbiota of children with newly diagnosed Crohn’s disease. Clin Transl Gastroenterol. 2015;6:e71.PubMedPubMedCentralGoogle Scholar
  95. 95.
    Weimann A, Braga M, Carli F, Higashiguchi T, Hübner M, Klek S, et al. ESPEN guideline: clinical nutrition in surgery. Clin Nutr. 2017;36:623–50.PubMedGoogle Scholar
  96. 96.
    Dignass AU. Mechanisms and modulation of intestinal epithelial repair. Inflamm Bowel Dis. 2001;7:68–77.PubMedGoogle Scholar
  97. 97.
    Karrasch T, Jobin C. Wound healing responses at the gastrointestinal epithelium: a close look at novel regulatory factors and investigative approaches. Z Gastroenterol. 2009;47:1221–9.PubMedGoogle Scholar
  98. 98.
    Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, Edberg S, Medzhitov R. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell. 2004;118:229–41.PubMedGoogle Scholar
  99. 99.
    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;53:1069–75.PubMedGoogle Scholar
  100. 100.
    Desai MS, Seekatz AM, Koropatkin NM, Kamada N, Hickey CA, Wolter M, et al. A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell. 2016;167:1339–53 e21.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Surgery, Perelman School of MedicineHospital of the University of PennsylvaniaPhiladelphiaUSA
  2. 2.Division of Gastroenterology, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA

Personalised recommendations