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Pathophysiology and protective approaches of gut injury in critical illness

  • Received : 2020.08.10
  • Accepted : 2020.08.31
  • Published : 2021.01.31

Abstract

The gut is a complex organ that has played an important role in digestion, absorption, endocrine functions, and immunity. The gut mucosal barriers consist of the immunologic barrier and nonimmunologic barrier. During critical illnesses, the gut is susceptible to injury due to the induction of intestinal hyperpermeability. Gut hyperpermeability and barrier dysfunction may lead to systemic inflammatory response syndrome. Additionally, gut microbiota are altered during critical illnesses. The etiology of such microbiome alterations in critical illnesses is multifactorial. The interaction or systemic host defense modulation between distant organs and the gut microbiome is increasingly studied in disease research. No treatment modality exists to significantly enhance the gut epithelial integrity, permeability, or mucus layer in critically ill patients. However, multiple helpful approaches including clinical and preclinical strategies exist. Enteral nutrition is associated with an increased mucosal barrier in animal and human studies. The trophic effects of enteral nutrition might help to maintain the intestinal physiology, prevent atrophy of gut villi, reduce intestinal permeability, and protect against ischemia-reperfusion injury. The microbiome approach such as the use of probiotics, fecal microbial transplantation, and selective decontamination of the digestive tract has been suggested. However, its evidence does not have a high quality. To promote rapid hypertrophy of the small bowel, various factors have been reported, including the epidermal growth factor, membrane permeant inhibitor of myosin light chain kinase, mucus surrogate, pharmacologic vagus nerve agonist, immune-enhancing diet, and glucagon-like peptide-2 as preclinical strategies. However, the evidence remains unclear.

Keywords

References

  1. Helander HF, Fandriks L. Surface area of the digestive tract: revisited. Scand J Gastroenterol 2014;49:681-9. https://doi.org/10.3109/00365521.2014.898326
  2. Allaire JM, Crowley SM, Law HT, Chang SY, Ko HJ, Vallance BA. The intestinal epithelium: central coordinator of mucosal immunity. Trends Immunol 2018;39:677-96. https://doi.org/10.1016/j.it.2018.04.002
  3. Otani S, Coopersmith CM. Gut integrity in critical illness. J Intensive Care 2019;7:17. https://doi.org/10.1186/s40560-019-0372-6
  4. Knoop KA, Newberry RD. Goblet cells: multifaceted players in immunity at mucosal surfaces. Mucosal Immunol 2018;11: 1551-7. https://doi.org/10.1038/s41385-018-0039-y
  5. Gerbe F, Sidot E, Smyth DJ, Ohmoto M, Matsumoto I, Dardalhon V, et al. Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites. Nature 2016;529:226-30. https://doi.org/10.1038/nature16527
  6. Townsend CM, Sabiston DC, Beauchamp RD, Evers BM, Mattox KL. Sabiston textbook of surgery: the biological basis of modern surgical practice. 20th ed. Philadelphia (PA): Elsevier; 2017.
  7. Coopersmith CM, Stromberg PE, Davis CG, Dunne WM, Amiot DM 2nd, Karl IE, et al. Sepsis from Pseudomonas aeruginosa pneumonia decreases intestinal proliferation and induces gut epithelial cell cycle arrest. Crit Care Med 2003;31:1630-7. https://doi.org/10.1097/01.CCM.0000055385.29232.11
  8. Meng M, Klingensmith NJ, Liang Z, Lyons JD, Fay KT, Chen CW, et al. Regulators of intestinal epithelial migration in sepsis. Shock 2019;51:88-96. https://doi.org/10.1097/SHK.0000000000001117
  9. Qin X, Caputo FJ, Xu DZ, Deitch EA. Hydrophobicity of mucosal surface and its relationship to gut barrier function. Shock 2008;29:372-6. https://doi.org/10.1097/SHK.0b013e3181453f4e
  10. Cook SI, Sellin JH. Review article: short chain fatty acids in health and disease. Aliment Pharmacol Ther 1998;12:499-507. https://doi.org/10.1046/j.1365-2036.1998.00337.x
  11. Morrison DJ, Preston T. Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes 2016;7:189-200. https://doi.org/10.1080/19490976.2015.1134082
  12. Dickson RP. The microbiome and critical illness. Lancet Respir Med 2016;4:59-72. https://doi.org/10.1016/S2213-2600(15)00427-0
  13. Haak BW, Levi M, Wiersinga WJ. Microbiota-targeted therapies on the intensive care unit. Curr Opin Crit Care 2017;23:167-74. https://doi.org/10.1097/MCC.0000000000000389
  14. Klingensmith NJ, Coopersmith CM. The gut as the motor of multiple organ dysfunction in critical illness. Crit Care Clin 2016;32:203-12. https://doi.org/10.1016/j.ccc.2015.11.004
  15. Pamer EG. Resurrecting the intestinal microbiota to combat antibiotic-resistant pathogens. Science 2016;352:535-8. https://doi.org/10.1126/science.aad9382
  16. Reintam A, Parm P, Kitus R, Kern H, Starkopf J. Gastrointestinal symptoms in intensive care patients. Acta Anaesthesiol Scand 2009;53:318-24. https://doi.org/10.1111/j.1399-6576.2008.01860.x
  17. Piton G, Belon F, Cypriani B, Regnard J, Puyraveau M, Manzon C, et al. Enterocyte damage in critically ill patients is associated with shock condition and 28-day mortality. Crit Care Med 2013;41:2169-76. https://doi.org/10.1097/CCM.0b013e31828c26b5
  18. Clark JA, Coopersmith CM. Intestinal crosstalk: a new paradigm for understanding the gut as the "motor" of critical illness. Shock 2007;28:384-93. https://doi.org/10.1097/shk.0b013e31805569df
  19. Meng M, Klingensmith NJ, Coopersmith CM. New insights into the gut as the driver of critical illness and organ failure. Curr Opin Crit Care 2017;23:143-8. https://doi.org/10.1097/MCC.0000000000000386
  20. Chiu CJ, McArdle AH, Brown R, Scott HJ, Gurd FN. Intestinal mucosal lesion in low-flow states. I. A morphological, hemodynamic, and metabolic reappraisal. Arch Surg 1970;101:478-83. https://doi.org/10.1001/archsurg.1970.01340280030009
  21. Reintam Blaser A, Malbrain ML, Starkopf J, Fruhwald S, Jakob SM, de Waele J, et al. Gastrointestinal function in intensive care patients: terminology, definitions and management. Recommendations of the ESICM Working Group on Abdominal Problems. Intensive Care Med 2012;38:384-94. https://doi.org/10.1007/s00134-011-2459-y
  22. Li H, Zhang D, Wang Y, Zhao S. Association between acute gas trointestinal injury grading system and disease severity and prognosis in critically ill patients: a multicenter, prospective, observational study in China. J Crit Care 2016;36:24-8. https://doi.org/10.1016/j.jcrc.2016.05.001
  23. Stratakis CA, Chrousos GP. Neuroendocrinology and pathophysiology of the stress system. Ann N Y Acad Sci 1995;771:1-18. https://doi.org/10.1111/j.1749-6632.1995.tb44666.x
  24. Gue M, Peeters T, Depoortere I, Vantrappen G, Bueno L. Stress-induced changes in gastric emptying, postprandial motility, and plasma gut hormone levels in dogs. Gastroenterology 1989;97:1101-7. https://doi.org/10.1016/0016-5085(89)91678-8
  25. Richardson RS, Norton LW, Sales JE, Eiseman B. Gastric blood flow in endotoxin-induced stress ulcer. Arch Surg 1973;106: 191-5. https://doi.org/10.1001/archsurg.1973.01350140049015
  26. Wallon C, Yang PC, Keita AV, Ericson AC, McKay DM, Sherman PM, et al. Corticotropin-releasing hormone (CRH) regulates macromolecular permeability via mast cells in normal human colonic biopsies in vitro. Gut 2008;57:50-8. https://doi.org/10.1136/gut.2006.117549
  27. Deitch EA. Gut-origin sepsis: evolution of a concept. Surgeon 2012;10:350-6. https://doi.org/10.1016/j.surge.2012.03.003
  28. Krejci V, Hiltebrand LB, Sigurdsson GH. Effects of epinephrine, norepinephrine, and phenylephrine on microcirculatory blood flow in the gastrointestinal tract in sepsis. Crit Care Med 2006;34:1456-63. https://doi.org/10.1097/01.CCM.0000215834.48023.57
  29. Chung DH, Evers BM, Townsend CM Jr, Huang KF, Shimoda I, Herndon DN, et al. Burn-induced transcriptional regulation of small intestinal ornithine decarboxylase. Am J Surg 1992;163:157-62. https://doi.org/10.1016/0002-9610(92)90269-W
  30. Klingensmith NJ, Fay KT, Lyons JD, Chen CW, Otani S, Liang Z, et al. Chronic alcohol ingestion worsens survival and alters gut epithelial apoptosis and CD8+ T cell function after pseudomonas aeruginosa pneumonia-induced sepsis. Shock 2019;51: 453-63. https://doi.org/10.1097/SHK.0000000000001163
  31. Fox AC, Robertson CM, Belt B, Clark AT, Chang KC, Leathersich AM, et al. Cancer causes increased mortality and is associated with altered apoptosis in murine sepsis. Crit Care Med 2010;38:886-93. https://doi.org/10.1097/CCM.0b013e3181c8fdb1
  32. Li H, Chen Y, Huo F, Wang Y, Zhang D. Association between acute gastrointestinal injury and biomarkers of intestinal barrier function in critically ill patients. BMC Gastroenterol 2017;17:45. https://doi.org/10.1186/s12876-017-0603-z
  33. Lankelma JM, van Vught LA, Belzer C, Schultz MJ, van der Poll T, de Vos WM, et al. Critically ill patients demonstrate large interpersonal variation in intestinal microbiota dysregulation: a pilot study. Intensive Care Med 2017;43:59-68. https://doi.org/10.1007/s00134-016-4613-z
  34. Burgstad CM, Besanko LK, Deane AM, Nguyen NQ, Saadat-Gilani K, Davidson G, et al. Sucrose malabsorption and impaired mucosal integrity in enterally fed critically ill patients: a prospective cohort observational study. Crit Care Med 2013; 41:1221-8. https://doi.org/10.1097/CCM.0b013e31827ca2fa
  35. Alverdy JC, Krezalek MA. Collapse of the microbiome, emergence of the pathobiome, and the immunopathology of sepsis. Crit Care Med 2017;45:337-47. https://doi.org/10.1097/CCM.0000000000002172
  36. Sonnenburg JL, Backhed F. Diet-microbiota interactions as moderators of human metabolism. Nature 2016;535:56-64. https://doi.org/10.1038/nature18846
  37. Wischmeyer PE, McDonald D, Knight R. Role of the microbiome, probiotics, and 'dysbiosis therapy' in critical illness. Curr Opin Crit Care 2016;22:347-53. https://doi.org/10.1097/MCC.0000000000000321
  38. McDonald D, Ackermann G, Khailova L, Baird C, Heyland D, Kozar R, et al. Extreme dysbiosis of the microbiome in critical illness. mSphere 2016;1:e00199-16.
  39. Levy M, Blacher E, Elinav E. Microbiome, metabolites and host immunity. Curr Opin Microbiol 2017;35:8-15. https://doi.org/10.1016/j.mib.2016.10.003
  40. Jacobs MC, Haak BW, Hugenholtz F, Wiersinga WJ. Gut microbiota and host defense in critical illness. Curr Opin Crit Care 2017;23:257-63. https://doi.org/10.1097/MCC.0000000000000424
  41. Magnotti LJ, Upperman JS, Xu DZ, Lu Q, Deitch EA. Gut-derived mesenteric lymph but not portal blood increases endothelial cell permeability and promotes lung injury after hemorrhagic shock. Ann Surg 1998;228:518-27. https://doi.org/10.1097/00000658-199810000-00008
  42. Deitch EA, Xu DZ, Lu Q. Gut lymph hypothesis of early shock and trauma-induced multiple organ dysfunction syndrome: a new look at gut origin sepsis. J Organ Dysfunct 2009;2:70-9. https://doi.org/10.1080/17471060600551772
  43. Carabotti M, Scirocco A, Maselli MA, Severi C. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol 2015;28:203-9.
  44. Foster JA, McVey Neufeld KA. Gut-brain axis: how the microbiome influences anxiety and depression. Trends Neurosci 2013;36:305-12. https://doi.org/10.1016/j.tins.2013.01.005
  45. Andrade-Oliveira V, Amano MT, Correa-Costa M, Castoldi A, Felizardo RJ, de Almeida DC, et al. Gut bacteria products prevent AKI induced by ischemia-reperfusion. J Am Soc Nephrol 2015;26:1877-88. https://doi.org/10.1681/ASN.2014030288
  46. Emal D, Rampanelli E, Stroo I, Butter LM, Teske GJ, Claessen N, et al. Depletion of gut microbiota protects against renal ischemia-reperfusion injury. J Am Soc Nephrol 2017;28:1450-61. https://doi.org/10.1681/ASN.2016030255
  47. Tilg H, Cani PD, Mayer EA. Gut microbiome and liver diseases. Gut 2016;65:2035-44. https://doi.org/10.1136/gutjnl-2016-312729
  48. Kazamias P, Kotzampassi K, Koufogiannis D, Eleftheriadis E. Influence of enteral nutrition-induced splanchnic hyperemia on the septic origin of splanchnic ischemia. World J Surg 1998; 22:6-11. https://doi.org/10.1007/s002689900341
  49. Purcell PN, Davis K Jr, Branson RD, Johnson DJ. Continuous duodenal feeding restores gut blood flow and increases gut oxygen utilization during PEEP ventilation for lung injury. Am J Surg 1993;165:188-93. https://doi.org/10.1016/S0002-9610(05)80424-6
  50. Alverdy JC, Aoys E, Moss GS. Total parenteral nutrition promotes bacterial translocation from the gut. Surgery 1988;104:185-90.
  51. Groos S, Hunefeld G, Luciano L. Parenteral versus enteral nutrition: morphological changes in human adult intestinal mucosa. J Submicrosc Cytol Pathol 1996;28:61-74.
  52. Schmidt H, Martindale R. The gastrointestinal tract in critical illness. Curr Opin Clin Nutr Metab Care 2001;4:547-51. https://doi.org/10.1097/00075197-200111000-00015
  53. Zhang D, Li H, Li Y, Qu L. Gut rest strategy and trophic feeding in the acute phase of critical illness with acute gastrointestinal injury. Nutr Res Rev 2019;32:176-82. https://doi.org/10.1017/S0954422419000027
  54. McClave SA, Taylor BE, Martindale RG, Warren MM, Johnson DR, Braunschweig C, et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr 2016;40:159-211. https://doi.org/10.1177/0148607115621863
  55. Boullata JI, Carrera AL, Harvey L, Escuro AA, Hudson L, Mays A, et al. ASPEN safe practices for enteral nutrition therapy. JPEN J Parenter Enteral Nutr 2017;41:15-103. https://doi.org/10.1177/0148607116673053
  56. Seol EM, Kwon KS, Kim JG, Kim JT, Kim J, Moon SM, et al. Nutritional therapy related complications in hospitalized adult patients: a Korean multicenter trial. J Clin Nutr 2019;11:12-22. https://doi.org/10.15747/jcn.2019.11.1.12
  57. Reignier J, Darmon M, Sonneville R, Borel AL, Garrouste-Orgeas M, Ruckly S, et al. Impact of early nutrition and feeding route on outcomes of mechanically ventilated patients with shock: a post hoc marginal structural model study. Intensive Care Med 2015;41:875-86. https://doi.org/10.1007/s00134-015-3730-4
  58. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 2013;39:165-228. https://doi.org/10.1007/s00134-012-2769-8
  59. Weng H, Li JG, Mao Z, Feng Y, Wang CY, Ren XQ, et al. Probiotics for preventing ventilator-associated pneumonia in mechanically ventilated patients: a meta-analysis with trial sequential analysis. Front Pharmacol 2017;8:717. https://doi.org/10.3389/fphar.2017.00717
  60. Klingensmith NJ, Yoseph BP, Liang Z, Lyons JD, Burd EM, Margoles LM, et al. Epidermal growth factor improves intestinal integrity and survival in murine sepsis following chronic alcohol ingestion. Shock 2017;47:184-92. https://doi.org/10.1097/SHK.0000000000000709
  61. Townsend CM, Sabiston DC. Sabiston textbook of surgery: the biological basis of modern surgical practice. 16th ed. Philadelphia (PA): WB Saunders; 2001.
  62. Zahs A, Bird MD, Ramirez L, Turner JR, Choudhry MA, Kovacs EJ, et al. Inhibition of long myosin light-chain kinase activation alleviates intestinal damage after binge ethanol exposure and burn injury. Am J Physiol Gastrointest Liver Physiol 2012; 303:G705-12. https://doi.org/10.1152/ajpgi.00157.2012
  63. Fishman JE, Sheth SU, Levy G, Alli V, Lu Q, Xu D, et al. Intraluminal nonbacterial intestinal components control gut and lung injury after trauma hemorrhagic shock. Ann Surg 2014; 260:1112-20. https://doi.org/10.1097/SLA.0000000000000631
  64. Langness S, Costantini TW, Morishita K, Eliceiri BP, Coimbra R. Modulating the biologic activity of mesenteric lymph after traumatic shock decreases systemic inflammation and end organ injury. PLoS One 2016;11:e0168322. https://doi.org/10.1371/journal.pone.0168322

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