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Cited by 166Sepsis Diagnosis and TreatmentClinical Nutrition and GastroenterologyGut microbiota and health

New insights into the gut as the driver of critical illness and organ failure

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Meng, Mei, Klingensmith, Nathan J., Coopersmith, Craig M.·2017·Current Opinion in Critical Care
DOI 10.1097/mcc.0000000000000386PMC PMC5373099
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Abstract

Purpose of review: The gut has long been hypothesized to be the ‘motor’ of multiple organ dysfunction syndrome. This review serves as an update on new data elucidating the role of the gut as the propagator of organ failure in critical illness. Recent findings: Under basal conditions, the gut absorbs nutrients and serves as a barrier that prevents approximately 40 trillion intraluminal microbes and their products from causing host injury. However, in critical illness, gut integrity is disrupted with hyperpermeability and increased epithelial apoptosis, allowing contamination of extraluminal sites that are ordinarily sterile. These alterations in gut integrity are further exacerbated in the setting of preexisting comorbidities. The normally commensal microflora is also altered in critical illness, with increases in microbial virulence and decreases in diversity, which leads to further pathologic responses within the host. Summary: All components of the gut are adversely impacted by critical illness. Gut injury can not only propagate local damage, but can also cause distant injury and organ failure. Understanding how the multifaceted components of the gut interact and how these are perturbed in critical illness may play an important role in turning off the ‘motor’ of multiple organ dysfunction syndrome in the future.

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  • Gastrointestinal dysfunction has a bidirectional relationship with other organ dysfunctions or failures, creating a cycle in which worsening gut function promotes further systemic deterioration.

    “Thus, GI dysfunction has a bidirectional relationship with other organ dysfunctions/failures, creating a cycle in which worsening gut function promotes further systemic deterioration (Fig. 1) [22].”

    From Gastrointestinal function and nutritional interventions in septic shock (2025) · cites this paper as [22]

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  1. [1]Carrico CJ Meakins JL Marshall JC Multiple-organ-failure syndrome. The gastrointestinal tract: the “motor” of MOF Arch Surg 1986 2 121 2 196 208 3484944
  2. [2]Helander HF Fandriks L Surface area of the digestive tract - revisited Scand J Gastroenterol 2014 6 49 6 681 9 24694282
  3. Sender R Fuchs S Milo R Are We Really Vastly Outnumbered? Revisiting the Ratio of Bacterial to Host Cells in Humans Cell 2016 1 28 164 3 337 40 This study describes the number of microbes living inside a human and refutes earlier commonly quoted data that there are many more microorganisms living inside a host than cells of host origin 26824647
  4. [4]Thome JJ Yudanin N Ohmura Y Spatial map of human T cell compartmentalization and maintenance over decades of life Cell 2014 11 6 159 4 814 28 25417158 PMC4243051
  5. [5]Reintam BA Poeze M Malbrain ML Gastrointestinal symptoms during the first week of intensive care are associated with poor outcome: a prospective multicentre study Intensive Care Med 2013 5 39 5 899 909 23370829 PMC3625421
  6. [6]Piton G Belon F Cypriani B Enterocyte damage in critically ill patients is associated with shock condition and 28-day mortality Crit Care Med 2013 9 41 9 2169 76 23782971
  7. Piton G Capellier G Biomarkers of gut barrier failure in the ICU Curr Opin Crit Care 2016 4 22 2 152 60 This review covers emerging biomarkers of intestinal barrier failure in critically ill patients and their potential utility 26808138
  8. [8]Klingensmith NJ Coopersmith CM The Gut as the Motor of Multiple Organ Dysfunction in Critical Illness Crit Care Clin 2016 4 32 2 203 12 27016162 PMC4808565
  9. [9]Mittal R Coopersmith CM Redefining the gut as the motor of critical illness Trends Mol Med 2014 4 20 4 214 23 24055446 PMC3959633
  10. [10]Coopersmith CM Chang KC Swanson PE Overexpression of Bcl-2 in the intestinal epithelium improves survival in septic mice Crit Care Med 2002 1 30 1 195 201 11902262
  11. [11]Dominguez JA Vithayathil PJ Khailova L Epidermal growth factor improves survival and prevents intestinal injury in a murine model of pseudomonas aeruginosa pneumonia Shock 2011 10 36 4 381 9 21701422 PMC3175258
  12. Yoseph BP Klingensmith NJ Liang Z Mechanisms of Intestinal Barrier Dysfunction in Sepsis Shock 2016 7 46 1 52 9 This study examines timing of gut barrier failure and mechanisms of gut barrier failure after both CLP and Pseudomonas aeruginosa pneumonia. Both models of sepsis generally share similar alterations in tight junction mediators; however, model-specific differences are also observed 27299587 PMC4910519
  13. [13]Li Q Zhang Q Wang C Disruption of tight junctions during polymicrobial sepsis in vivo J Pathol 2009 6 218 2 210 21 19235836
  14. [14]Deitch EA Gut-origin sepsis: evolution of a concept Surgeon 2012 12 10 6 350 6 22534256 PMC3413774
  15. [15]Yi J Slaughter A Kotter CV Clean case of systemic injury: mesenteric lymph after hemorrhagic shock elicits a sterile inflammatory response Shock 2015 10 44 4 336 40 26196840 PMC4575624
  16. [16]Beck MK Jensen AB Nielsen AB Diagnosis trajectories of prior multi-morbidity predict sepsis mortality Sci Rep 2016 11 4 6 36624 27812043 PMC5095673
  17. Lyons JD Mittal R Fay KT Murine Lung Cancer Increases CD4+ T Cell Apoptosis and Decreases Gut Proliferative Capacity in Sepsis PLoS ONE 2016 11 3 e0149069 This study describes a model of pre-existing lung cancer prior to the onset of sepsis and compares it to previously healthy mice with the same septic insult. The cancer/septic mice have decreased gut proliferation as well as increased T cell apoptosis 27018973 PMC4809578
  18. [18]Fox AC Robertson CM Belt B Cancer causes increased mortality and is associated with altered apoptosis in murine sepsis Crit Care Med 2010 3 38 3 886 93 20009755 PMC2825291
  19. [19]Yoseph BP Breed E Overgaard CE Chronic alcohol ingestion increases mortality and organ injury in a murine model of septic peritonitis PLoS ONE 2013 8 5 e62792 23717394 PMC3661585
  20. Klingensmith NJ Yoseph BP Liang Z Epidermal Growth Factor Improves Intestinal Integrity and Survival in Murine Sepsis Following Chronic Alcohol Ingestion Shock 2016 7 25 This study examines the impact of giving systemic epidermal growth factor to mice with 12 weeks of chronic alcohol ingestion prior to the onset of sepsis. Epidermal growth factor improves gut intergrity and survival in alcohol/septic mice but the response is blunted in comparison to previously healthy/septic mice PMC5235949 27465753
  21. [21]Turnbull IR Buchman TG Javadi P Age disproportionately increases sepsis-induced apoptosis in the spleen and gut epithelium Shock 2004 10 22 4 364 8 15377893
  22. [22]Dominguez JA Xie Y Dunne WM Intestine-specific Mttp deletion decreases mortality and prevents sepsis-induced intestinal injury in a murine model of Pseudomonas aeruginosa pneumonia PLoS ONE 2012 7 11 e49159 23145105 PMC3493497
  23. [23]Liang Z Xie Y Dominguez JA Intestine-specific deletion of microsomal triglyceride transfer protein increases mortality in aged mice PLoS ONE 2014 9 7 e101828 25010671 PMC4092051
  24. [24]Xu Z Knight R Dietary effects on human gut microbiome diversity Br J Nutr 2015 1 113 Suppl S1 S5 PMC4405705 25498959
  25. [25]Ackerman J The ultimate social network Sci Am 2012 6 306 6 36 43 22649992
  26. Krezalek MA Defazio J Zaborina O The Shift of an Intestinal “Microbiome” to a “Pathobiome” Governs the Course and Outcome of Sepsis Following Surgical Injury Shock 2016 5 45 5 475 82 This review is a comprehensive state of the art description of how dysbiosis occur following surgical illness and worsens outcome 26863118 PMC4833524
  27. McDonald D Ackermann G Khailova L Extreme Dysbiosis of the Microbiome in Critical Illness mSphere 2016 7 1 4 This is the largest study of the microbiome to date (115 patients) in critical illness, demonstrating significant and persistent dysbiosis PMC5007431 27602409
  28. [29]Hayakawa M Asahara T Henzan N Dramatic changes of the gut flora immediately after severe and sudden insults Dig Dis Sci 2011 8 56 8 2361 5 21384123
  29. [30]Babrowski T Romanowski K Fink D The intestinal environment of surgical injury transforms Pseudomonas aeruginosa into a discrete hypervirulent morphotype capable of causing lethal peritonitis Surgery 2013 1 153 1 36 43 22862900 PMC3521093
  30. Manzanares W Lemieux M Langlois PL Wischmeyer PE Probiotic and synbiotic therapy in critical illness: a systematic review and meta-analysis Crit Care 2016 8 19 19 262 Meta-analysis of probiotics and synbiotics in critical care demonstrating a decrease in ventilator associated pneumonia and infections without an effect on mortality, length of stay or diarrhea 27538711 PMC4991010
  31. Dickson RP The microbiome and critical illness Lancet Respir Med 2016 1 4 1 59 72 This is a comprehensive overview on the role of the microbiome in critical illness 26700442 PMC4752077
  32. [33]Chapman BC Moore HB Overbey DM Fecal microbiota transplant in patients with Clostridium difficile infection: A systematic review J Trauma Acute Care Surg 2016 10 81 4 756 64 27648772
  33. Han S Shannahan S Pellish R Fecal Microbiota Transplant: Treatment Options for Clostridium difficile Infection in the Intensive Care Unit J Intensive Care Med 2016 10 31 9 577 86 This is an overview of the treatment fo Clostridia difficile infection in the ICU including fecal microbiota transplant. While FMT is still experimental inside the ICU, this review gives a list of possilbe indications 26141116
  34. [35]Li Q Wang C Tang C Successful treatment of severe sepsis and diarrhea after vagotomy utilizing fecal microbiota transplantation: a case report Crit Care 2015 2 9 19 37 25881250 PMC4346118
  35. [36]Wei Y Yang J Wang J Successful treatment with fecal microbiota transplantation in patients with multiple organ dysfunction syndrome and diarrhea following severe sepsis Crit Care 2016 10 18 20 1 332 27751177 PMC5067912
  36. [37]Hammer AM Morris NL Earley ZM Choudhry MA The First Line of Defense: The Effects of Alcohol on Post-Burn Intestinal Barrier, Immune Cells, and Microbiome Alcohol Res 2015 37 2 209 22 26695746 PMC4590618
  37. [38]Vachharajani VT Liu T Brown CM SIRT1 inhibition during the hypoinflammatory phenotype of sepsis enhances immunity and improves outcome J Leukoc Biol 2014 11 96 5 785 96 25001863 PMC4197566
  38. [40]Kober OI Ahl D Pin C gammadelta T-cell-deficient mice show alterations in mucin expression, glycosylation, and goblet cells but maintain an intact mucus layer Am J Physiol Gastrointest Liver Physiol 2014 4 1 306 7 G582 G593 24503767 PMC3962592
  39. [41]Costa MF de Negreiros CB Bornstein VU Murine IL-17+ Vgamma4 T lymphocytes accumulate in the lungs and play a protective role during severe sepsis BMC Immunol 2015 6 3 16 36 26037291 PMC4451961
  40. [42]Galley HF Lowes DA Thompson K Characterisation of gamma delta (gammadelta) T cell populations in patients with sepsis Cell Biol Int 2015 2 39 2 210 6 25196852
  41. [43]Shubin NJ Monaghan SF Heffernan DS A B and T lymphocyte attenuator expression on CD4+ T-cells associates with sepsis and subsequent infections in ICU patients Crit Care 2013 11 29 17 6 R276 24289156 PMC4057112
  42. [44]Chang K Svabek C Vazquez-Guillamet C Targeting the programmed cell death 1: programmed cell death ligand 1 pathway reverses T cell exhaustion in patients with sepsis Crit Care 2014 1 4 18 1 R3 24387680 PMC4056005
  43. Wu Y Chung CS Chen Y Novel Role for Programmed Cell Death Receptor Ligand-1 (PD-L1) in Sepsis-Induced Intestinal Dysfunction Mol Med 2016 10 25 22 This study demonstrates that PD-L1 is upregulated on the gut epithelium in sepsis and PD-L1 knockout animals have improved intestinal permeability PMC5263053 27782294
  44. Du X Meng Q Sharif A Surfactant Proteins SP-A and SP-D Ameliorate Pneumonia Severity and Intestinal Injury in a Murine Model of Staphylococcus Aureus Pneumonia Shock 2016 8 46 2 164 72 This study demonstrates that Surfactant proteins SP-A and SP-D play an important role in mediating gut epithelial apoptosis in Staphylococcus aureus pneumonia, as sepsis-induced cell death is increased after knocking out these proteins 26849628
  45. [48]Tilg H Cani PD Mayer EA Gut microbiome and liver diseases Gut 2016 10 8 27802157
  46. [49]Andrade-Oliveira V Amano MT Correa-Costa M Gut Bacteria Products Prevent AKI Induced by Ischemia-Reperfusion J Am Soc Nephrol 2015 8 26 8 1877 88 25589612 PMC4520159
  47. [50]Khoury T Tzukert K Abel R The gut-kidney axis in chronic renal failure: A new potential target for therapy Hemodial Int 2016 9 16 27634464
  48. Kennedy PJ Cryan JF Dinan TG Clarke G Kynurenine pathway metabolism and the microbiota-gut-brain axis Neuropharmacology 2017 1 112 Pt B 399 412 This paper reviews the connections between the gut microbiome and the brain. While not focused on critical care, this is outlines an axis that is frequently overlooked and could have significant clinical importance 27392632

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Authors
Meng, M., Klingensmith, N. J., & Coopersmith, C. M.
Affiliations
  • Shandong University (CN)
  • Emory University (US)
Corresponding author
Coopersmith, Craig M.
ORCID
Venue
Current Opinion in Critical Care
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2017-04
Volume
23
Issue
2
Pages
143-148
ISSN
  • 1070-5295 (ISSN-L)
  • 1531-7072
DOI
10.1097/mcc.0000000000000386
PMC
PMC5373099
OpenAlex
W2573440234
Cited by
166
References
3
Citations by year
2026: 11 · 2025: 18 · 2024: 16 · 2023: 18 · 2022: 20 · 2021: 23 · 2020: 27 · 2019: 20 · 2018: 9 · 2017: 4
FWCI
2.18
Type
journal article
Language
en
Open access
Locations
  • Current Opinion in Critical Care (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of General Medical Sciences (R01GM072808, R01GM113228, R01GM109779, R01GM104323, T32GM095442)
Topics
  • Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
  • Health Sciences › Nursing › Nutrition and Dietetics › Clinical Nutrition and Gastroenterology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Keywords
intestinal barrier dysfunction, multiple organ failure, organ failure, critical illness, intestinal permeability, epithelial apoptosis, commensal microbiota, microbial virulence, gut dysbiosis, comorbidities, systemic inflammation
MeSH terms
Humans, Intestinal Mucosa, Multiple Organ Failure, Critical Illness, Sepsis, Gastrointestinal Tract, Microbiota

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