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Meisen S, Schütte L, Balmayor E, Halbgebauer R, Huber-Lang M. TRAUMA AND THE ENTEROCYTE: DISTURBANCE OF COMMUNICATION AND DELINEATION. Shock 2025; 63:677-687. [PMID: 40239221 DOI: 10.1097/shk.0000000000002564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/18/2025]
Abstract
ABSTRACT The enterocyte as major building stone of the intestinal barrier plays a central role in maintaining cellular homeostasis and mediating host-environment interactions. Trauma, whether direct or remote, disrupts enterocyte function through complex mechanisms including impaired oxygen delivery, disturbed intercellular communication, and compromised nutrient uptake and metabolite clearance. These changes may lead to barrier dysfunction and altered repair mechanisms, facilitating systemic inflammation and remote organ injury. The failure of communication pathways-both within enterocytes and across epithelial networks-undermines coordinated responses to injury. Understanding these multifaceted perturbations reveals the enterocyte not merely as a passive victim but as an active participant in trauma-induced pathology. Emerging therapeutic strategies focus on enhancing mucosal repair via sealing agents, promoting epithelial proliferation, and restoring metabolic and signaling homeostasis. This review delineates the dynamic response of the enterocyte to trauma, highlighting opportunities for targeted interventions aimed at restoring intestinal integrity and function.
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Affiliation(s)
- Sophie Meisen
- Institute of Clinical and Experimental Trauma Immunology, Ulm University Medical Center, Ulm, Germany
| | - Lena Schütte
- Institute of Clinical and Experimental Trauma Immunology, Ulm University Medical Center, Ulm, Germany
| | - Elizabeth Balmayor
- Experimental Orthopaedics and Trauma Surgery, Department of Orthopaedics, Trauma and Reconstructive Surgery, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Aachen, Germany
| | - Rebecca Halbgebauer
- Institute of Clinical and Experimental Trauma Immunology, Ulm University Medical Center, Ulm, Germany
| | - Markus Huber-Lang
- Institute of Clinical and Experimental Trauma Immunology, Ulm University Medical Center, Ulm, Germany
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Beiter T, Erz G, Würden A, Nieß AM. Impact of moderate environmental heat stress during running exercise on circulating markers of gastrointestinal integrity in endurance athletes. Physiol Rep 2025; 13:e70305. [PMID: 40170530 PMCID: PMC11962213 DOI: 10.14814/phy2.70305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Revised: 03/21/2025] [Accepted: 03/23/2025] [Indexed: 04/03/2025] Open
Abstract
In the present study, we aimed to determine the effect of moderate ambient heat stress on exercise-provoked patterns of "leaky gut" biomarkers and stress markers in well-trained athletes. Eleven triathletes performed a strenuous 1-h treadmill run, both under normal ambient conditions (N, 18-21°C) as well as under moderate heat environmental conditions (H, 28-30°C). Core body temperature (Tc), heart rate (HR), and rating of perceived exertion (RPE) significantly increased under both conditions, with significantly higher values during and after the H run. We observed a significant main effect of acute exercise on circulating leukocyte numbers, release of cell-free human DNA (cfDNA) but not bacterial DNA (bacDNA), and on plasma levels of intestinal fatty-acid binding protein (I-FABP), lipopolysaccharide-binding protein (LBP), endotoxin (LPS), and D-lactate. Exercising under H conditions accelerated the mobilization of circulating neutrophils and lymphocytes, and significantly affected the release of cfDNA, D-lactate, I-FABP, creatinine, and blood potassium levels. Multiple correlation analysis revealed a significant association between Tc, max and exercise-provoked release of cfDNA (r = 0.583, p = 0.012) as well as with I-FABP (r = 0.554, p = 0.026). Our data indicate that acute exercising and heat stress may not only affect paracellular but also transcellular intestinal permeability.
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Affiliation(s)
- Thomas Beiter
- Department of Sports MedicineUniversity Hospital TübingenTübingenGermany
| | - Gunnar Erz
- Department of Sports MedicineUniversity Hospital TübingenTübingenGermany
| | - Anna Würden
- Department of Sports MedicineUniversity Hospital TübingenTübingenGermany
| | - Andreas M. Nieß
- Department of Sports MedicineUniversity Hospital TübingenTübingenGermany
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Grafver I, Edström M, Seilitz J, Axelsson B, Pirouzram A, Hörer TM, Nilsson KF. Intestinal Fatty Acid-Binding Protein as a Potential Biomarker for Gastrointestinal Complications after Complex Endovascular Aortic Surgery. Ann Vasc Surg 2024; 106:176-183. [PMID: 38815905 DOI: 10.1016/j.avsg.2024.03.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 03/20/2024] [Accepted: 03/21/2024] [Indexed: 06/01/2024]
Abstract
BACKGROUND This study aimed to investigate the association between intestinal fatty acid-binding protein (I-FABP), acute gastrointestinal injury (AGI) grade, and gastrointestinal (GI) complications after fenestrated or branched endovascular aortic aneurysm repair. METHODS A total of 17 patients undergoing endovascular aortic repair for thoracoabdominal, juxtarenal, suprarenal, or pararenal aneurysm between May 2017 and September 2018 were enrolled. Blood samples were collected preoperatively and during postoperative intensive care. The blood samples were analyzed for I-FABP with enzyme-linked immunosorbent assay. Gastrointestinal function was assessed according to the AGI grade every day during postoperative intensive care. RESULTS Higher concentrations of I-FABP at 24 hr and 48 hr correlated to higher AGI grade on postoperative days 1, 2, and 3 (P = 0.032 and P = 0.048, P = 0.040 and P = 0.018, and P = 0.012 and P = 0.016, respectively). Patients who developed a GI complication within 90 days postoperatively had a higher overall AGI grade than those who did not develop a GI complication (P < 0.001), as well as higher concentrations of I-FABP at 48 hrs (P = 0.019). Patients developing GI dysfunction (AGI grade ≥2) had a higher frequency of complications (P = 0.009) and longer length of stay in the intensive care unit (P = 0.008). CONCLUSIONS In patients undergoing endovascular aortic repair for complex aneurysm increased postoperative plasma I-FABP concentrations and postoperative GI dysfunction, evaluated using the AGI grade, were associated with GI complications, indicating that these measures may be useful in the postoperative management of these patients.
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Affiliation(s)
- Isabelle Grafver
- Faculty of Medicine and Health, Department of Cardiothoracic and Vascular Surgery, Örebro University, Örebro University Hospital, Örebro, Sweden; School of Medical Sciences, Örebro University, Örebro, Sweden.
| | - Måns Edström
- Faculty of Medicine and Health, Department of Anaesthesiology and Intensive Care, Örebro University, Örebro University Hospital, Örebro, Sweden
| | - Jenny Seilitz
- Faculty of Medicine and Health, Department of Cardiothoracic and Vascular Surgery, Örebro University, Örebro University Hospital, Örebro, Sweden
| | - Birger Axelsson
- Faculty of Medicine and Health, Department of Cardiothoracic and Vascular Surgery, Örebro University, Örebro University Hospital, Örebro, Sweden
| | - Artai Pirouzram
- Department of Cardiothoracic and Vascular Surgery, Faculty of Medicine and Health Science, Linköping University, University Hospital Linköping, Linköping, Sweden
| | - Tal M Hörer
- Faculty of Medicine and Health, Department of Cardiothoracic and Vascular Surgery, Örebro University, Örebro University Hospital, Örebro, Sweden
| | - Kristofer F Nilsson
- Faculty of Medicine and Health, Department of Cardiothoracic and Vascular Surgery, Örebro University, Örebro University Hospital, Örebro, Sweden; School of Medical Sciences, Örebro University, Örebro, Sweden
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Farbu BH, Lydersen S, Mohus RM, Ueland T, Mollnes TE, Klepstad P, Langeland H. The detrimental effects of intestinal injury mediated by inflammation are limited in cardiac arrest patients: A prospective cohort study. Resusc Plus 2024; 18:100639. [PMID: 38666252 PMCID: PMC11043872 DOI: 10.1016/j.resplu.2024.100639] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 03/21/2024] [Accepted: 04/04/2024] [Indexed: 04/28/2024] Open
Abstract
Background Ischaemic intestines could be a driver of critical illness through an inflammatory response. We have previously published reports on a biomarker for intestinal injury, plasma Intestinal Fatty Acid Binding Protein (IFABP), and inflammatory biomarkers after out-of-hospital cardiac arrest (OHCA). In this post-hoc study we explored the potential indirect effects of intestinal injury mediated through the inflammatory response on organ dysfunction and mortality. Methods We measured IFABP and twenty-one inflammatory biomarkers in 50 patients at admission to intensive care unit after OHCA. First, we stratified patients on median IFABP and compared biomarkers between "low" and "high" IFABP. Second, by causal mediation analysis, we assessed effects of IFABP through the two most important inflammatory biomarkers, interleukin (IL)-6 and terminal complement complex (TCC), on day two circulatory variables, Sequential Organ Failure Assessment (SOFA)-score, and 30-day mortality. Results Cytokines and complement activation were higher in the high IFABP group. In mediation analysis, patients on the 75th percentile of IFABP, compared to the 25th percentile, had 53% (95% CI, 33-74; p < 0.001) higher risk of dying, where 13 (95% CI, 3-23; p = 0.01) percentage points were mediated through an indirect effect of IL-6. Similarly, the indirect effect of IFABP through IL-6 on SOFA-score was significant, but smaller than potential other effects. Effects through IL-6 on circulatory variables, and all effects through TCC, were not statistically significant and/or small. Conclusion Effects of intestinal injury mediated through inflammation on organ dysfunction and mortality were limited. Small, but significant, effects through IL-6 were noted.Trial registration: ClinicalTrials.gov: NCT02648061.
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Affiliation(s)
- Bjørn Hoftun Farbu
- Department of Anaesthesiology and Intensive Care Medicine, St. Olav's University Hospital Trondheim, Norway
- Institute of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Norwegian Air Ambulance Foundation, Department of Research and Development, Oslo, Norway
| | - Stian Lydersen
- Regional Centre for Child and Youth Mental Health and Child Welfare, Department of Mental Health, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Randi Marie Mohus
- Department of Anaesthesiology and Intensive Care Medicine, St. Olav's University Hospital Trondheim, Norway
- Institute of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Thor Ueland
- Thrombosis Research Center (TREC), Division of Internal Medicine, University hospital of North Norway, Tromsø, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Research Institute of Internal Medicine, Oslo University Hospital (Rikshospitalet), Oslo, Norway
| | - Tom Eirik Mollnes
- Department of Immunology, Oslo University Hospital and University of Oslo, Oslo, Norway
- Research Laboratory, Nordland Hospital, Bodø, Norway
| | - Pål Klepstad
- Department of Anaesthesiology and Intensive Care Medicine, St. Olav's University Hospital Trondheim, Norway
- Institute of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Halvor Langeland
- Department of Anaesthesiology and Intensive Care Medicine, St. Olav's University Hospital Trondheim, Norway
- Institute of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
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Tyszko M, Lemańska-Perek A, Śmiechowicz J, Tomaszewska P, Biecek P, Gozdzik W, Adamik B. Citrulline, Intestinal Fatty Acid-Binding Protein and the Acute Gastrointestinal Injury Score as Predictors of Gastrointestinal Failure in Patients with Sepsis and Septic Shock. Nutrients 2023; 15:2100. [PMID: 37432225 DOI: 10.3390/nu15092100] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 04/23/2023] [Accepted: 04/25/2023] [Indexed: 07/12/2023] Open
Abstract
Gastrointestinal (GI) failure can be both a cause of sepsis and a consequence of the systemic pro-inflammatory response in sepsis. Changes in biomarkers of enterocyte damage, citrulline and I-FABP (intestinal fatty acid binding protein), may indicate altered intestinal permeability and damage. The study group consisted of patients with sepsis (N = 28) and septic shock (N = 30); the control group included patients without infection (N = 10). Blood samples were collected for citrulline and I-FABP and a 4-point AGI score (acute GI injury score) was calculated to monitor GI function on days 1, 3, 5, 7, and 10. Citrulline concentrations in the study group were lower than in the control. Lower values were also noted in septic patients with shock when compared to the non-shock group throughout the study period. I-FABP was higher in the septic shock group than in the sepsis group only on days 1 and 3. Citrulline was lower in patients with GI failure (AGI III) when compared to AGI I/II, reaching significance on days 7 (p = 0.034) and 10 (p = 0.015); moreover, a higher AGI score was associated with an increased 28 day mortality (p = 0.038). The results indicate that citrulline measurements, along with the AGI assessment, have clinical potential in monitoring GI function and integrity in sepsis.
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Affiliation(s)
- Maciej Tyszko
- Clinical Department of Anesthesiology and Intensive Therapy, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland
| | - Anna Lemańska-Perek
- Department of Chemistry and Immunochemistry, Wroclaw Medical University, M. Sklodowskiej-Curie 48/50, 50-369 Wroclaw, Poland
| | - Jakub Śmiechowicz
- Clinical Department of Anesthesiology and Intensive Therapy, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland
| | - Paulina Tomaszewska
- Faculty of Mathematics and Information Science, Warsaw University of Technology, Koszykowa 75, 00-662 Warsaw, Poland
| | - Przemyslaw Biecek
- Faculty of Mathematics and Information Science, Warsaw University of Technology, Koszykowa 75, 00-662 Warsaw, Poland
- Faculty of Mathematics, Informatics and Mechanics, University of Warsaw, Banacha 2, 02-097 Warsaw, Poland
| | - Waldemar Gozdzik
- Clinical Department of Anesthesiology and Intensive Therapy, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland
| | - Barbara Adamik
- Clinical Department of Anesthesiology and Intensive Therapy, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland
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Voth M, Verboket R, Henrich D, Marzi I. L-FABP and NGAL are novel biomarkers for detection of abdominal injury and hemorrhagic shock. Injury 2023; 54:1246-1256. [PMID: 36621362 DOI: 10.1016/j.injury.2023.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 12/15/2022] [Accepted: 01/01/2023] [Indexed: 01/04/2023]
Abstract
INTRODUCTION Delayed diagnosis of abdominal injuries and hemorrhagic shock leads to secondary complications and high late mortality in severely traumatized patients. The liver fatty acid-binding protein (L-FABP) is expressed in intestine, liver and kidney; the neutrophil gelatinase-associated lipocalin (NGAL) in colon and kidney. We hypothesized that l-FABP is an early biomarker for abdominal injury and hemorrhagic shock and that l-FABP and NGAL are specific markers for detection of liver and/or kidney injuries. PATIENTS AND METHODS Traumatized patients with an age ≥18 years and an abdominal injury (AISabd≥2), independently from Injury Severity Score (ISS), were prospectively included from 04/2018 to 05/2021. 68 patients had an abdominal injury ("Abd") and 10 patients had an abdominal injury with hemorrhagic shock ("HS Abd"). 41 patients without abdominal injury and hemorrhagic shock but with an ISS ≥ 25 ("noAbd") were included as control group. Four abdominal subgroups with isolated organ injuries were defined. Plasma l-FABP and NGAL levels were measured at admission (ER) and up to two days post-trauma. RESULTS All patient groups had a median ISS≥25. In ER, median l-FABP levels were significantly higher in "HS Abd" group (1209.2 ng/ml [IQR=575.2-1780.3]) compared to "noAbd" group (36.4 ng/ml [IQR=14.8-88.5]), and to "Abd" group (41.4 ng/ml [IQR=18.0-235.5]), p<0.001. In matched-pair-analysis l-FABP levels in the group "Abd" were significantly higher (108.3 ng/ml [IQR=31.4-540.9]) compared to "noAbd" (26.4 ng/ml [IQR=15.5-88.8]), p = 0.0016. l-FABP correlated significantly with clinical parameters of hemorrhagic shock; the optimal cut-off level of l-FABP for detection was 334.3 ng/ml (sensitivity: 90%, specificity: 78%). Median l-FABP-levels were significantly higher in patients with isolated liver or kidney injuries and correlated significantly with AST, ALT and creatinine value. Median NGAL levels in the ER were significantly higher in "HS Abd" group (115.9 ng/ml [IQR=90.6-163.8]) compared to "noAbd" group (58.5 ng/ml [IQR=41.0-89.6],p<0.001) and "Abd" group (70.5 ng/ml [IQR=53.3-115.5], p<0.05). The group "Abd" showed significant higher median NGAL levels compared to "noAbd", p = 0.019. NGAL levels correlated significantly with clinical parameters of hemorrhagic shock. CONCLUSION L-FABP and NGAL are novel biomarkers for detection of abdominal trauma and hemorrhagic shock. l-FABP may be a useful and promising parameter in diagnosis of liver and kidney injuries, NGAL failed to achieve the same.
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Affiliation(s)
- M Voth
- Department of Trauma, Hand and Reconstructive Surgery, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany.
| | - R Verboket
- Department of Trauma, Hand and Reconstructive Surgery, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany
| | - D Henrich
- Department of Trauma, Hand and Reconstructive Surgery, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany
| | - I Marzi
- Department of Trauma, Hand and Reconstructive Surgery, University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany
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de Jong WJJ, El Moumni M, Wendt KW, Nijsten MW, Hulscher JBF. Utility of liver and intestinal fatty acid-binding proteins in diagnosing intra-abdominal injury in adult trauma patients: prospective clinical trial. Br J Surg 2022; 109:796-799. [PMID: 35583155 PMCID: PMC10364720 DOI: 10.1093/bjs/znac117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Revised: 02/28/2022] [Accepted: 03/28/2022] [Indexed: 08/02/2023]
Affiliation(s)
- Willem J J de Jong
- Correspondence to: Willem J. J. de Jong, Department of Surgery UMCG, HPC BA20, Postbus 30.001, 9700 RB, Groningen, the Netherlands (e-mail: )
| | - Mostafa El Moumni
- Department of Surgery, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
| | - Klaus W Wendt
- Department of Surgery, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
| | - Maarten W Nijsten
- Department of Critical Care, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
| | - Jan B F Hulscher
- Department of Surgery, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands
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Vollrath JT, Klingebiel F, Bläsius F, Greven J, Bolierakis E, Nowak AJ, Simic M, Hildebrand F, Marzi I, Relja B. I-FABP as a Potential Marker for Intestinal Barrier Loss in Porcine Polytrauma. J Clin Med 2022; 11:jcm11154599. [PMID: 35956214 PMCID: PMC9369469 DOI: 10.3390/jcm11154599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 07/28/2022] [Accepted: 08/02/2022] [Indexed: 12/01/2022] Open
Abstract
Polytrauma and concomitant hemorrhagic shock can lead to intestinal damage and subsequent multiple organ dysfunction syndrome. The intestinal fatty acid-binding protein (I-FABP) is expressed in the intestine and appears quickly in the circulation after intestinal epithelial cell damage. This porcine animal study investigates the I-FABP dynamics in plasma and urine after polytrauma. Furthermore, it evaluates to what extent I-FABP can also act as a marker of intestinal damage in a porcine polytrauma model. Eight pigs (Sus scrofa) were subjected to polytrauma which consisted of lung contusion, tibial fracture, liver laceration, and hemorrhagic shock followed by blood and fluid resuscitation and fracture fixation with an external fixator. Eight sham animals were identically instrumented but not injured. Afterwards, intensive care treatment including mechanical ventilation for 72 h followed. I-FABP levels in blood and urine were determined by ELISA. In addition, immunohistological staining for I-FABP, active caspase-3 and myeloperoxidase were performed after 72 h. Plasma and urine I-FABP levels were significantly increased shortly after trauma. I-FABP expression in intestinal tissue showed significantly lower expression in polytraumatized animals vs. sham. Caspase-3 and myeloperoxidase expression in the immunohistological examination were significantly higher in the jejunum and ileum of polytraumatized animals compared to sham animals. This study confirms a loss of intestinal barrier after polytrauma which is indicated by increased I-FABP levels in plasma and urine as well as decreased I-FABP levels in immunohistological staining of the intestine.
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Affiliation(s)
- Jan Tilmann Vollrath
- Department of Trauma, Hand and Reconstructive Surgery, Goethe University, 60596 Frankfurt, Germany
| | - Felix Klingebiel
- Department of Trauma, Hand and Reconstructive Surgery, Goethe University, 60596 Frankfurt, Germany
- Department of Trauma, University of Zurich, Universitätsspital Zurich, 8091 Zurich, Switzerland
- Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto von Guericke University, 39120 Magdeburg, Germany
| | - Felix Bläsius
- Department of Trauma and Reconstructive Surgery, RWTH Aachen University, 52074 Aachen, Germany
| | - Johannes Greven
- Department of Trauma and Reconstructive Surgery, RWTH Aachen University, 52074 Aachen, Germany
| | - Eftychios Bolierakis
- Department of Trauma and Reconstructive Surgery, RWTH Aachen University, 52074 Aachen, Germany
| | - Aleksander J. Nowak
- Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto von Guericke University, 39120 Magdeburg, Germany
| | - Marija Simic
- Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto von Guericke University, 39120 Magdeburg, Germany
| | - Frank Hildebrand
- Department of Trauma and Reconstructive Surgery, RWTH Aachen University, 52074 Aachen, Germany
| | - Ingo Marzi
- Department of Trauma, Hand and Reconstructive Surgery, Goethe University, 60596 Frankfurt, Germany
| | - Borna Relja
- Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto von Guericke University, 39120 Magdeburg, Germany
- Correspondence:
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Abstract
To date, much of the focus of gut-brain axis research has been on gut microbiota regulation of anxiety and stress-related behaviors. Much less attention has been directed to potential connections between gut microbiota and compulsive behavior. Here, we discuss a potential link between gut barrier dysfunction and compulsive behavior that is mediated through "type 2" rather than "type 1" inflammation. We examine connections between compulsive behavior and type 2 inflammation in Tourette syndrome, obsessive-compulsive disorder, autism, addiction, and post-traumatic stress disorder. Next, we discuss potential connections between gut barrier dysfunction, type 2 inflammation, and compulsive behavior. We posit a potential mechanism whereby gut barrier dysfunction-associated type 2 inflammation may drive compulsive behavior through histamine regulation of dopamine neurotransmission. Finally, we discuss the possibility of exploiting the greater accessibility of the gut relative to the brain in identifying targets to treat compulsive behavior disorders.
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Sturm R, Haag F, Janicova A, Xu B, Vollrath JT, Bundkirchen K, Dunay IR, Neunaber C, Marzi I, Relja B. Acute alcohol consumption increases systemic endotoxin bioactivity for days in healthy volunteers-with reduced intestinal barrier loss in female. Eur J Trauma Emerg Surg 2022; 48:1569-1577. [PMID: 33839799 PMCID: PMC9192383 DOI: 10.1007/s00068-021-01666-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 04/01/2021] [Indexed: 02/05/2023]
Abstract
OBJECTIVE Trauma is the most common cause of death among young adults. Alcohol intoxication plays a significant role as a cause of accidents and as a potent immunomodulator of the post-traumatic response to tissue injury. Polytraumatized patients are frequently at risk to developing infectious complications, which may be aggravated by alcohol-induced immunosuppression. Systemic levels of integral proteins of the gastrointestinal tract such as syndecan-1 or intestinal fatty acid binding proteins (FABP-I) reflect the intestinal barrier function. The exact impact of acute alcohol intoxication on the barrier function and endotoxin bioactivity have not been clarified yet. METHODS 22 healthy volunteers received a precisely defined amount of alcohol (whiskey-cola) every 20 min over a period of 4 h to reach the calculated blood alcohol concentration (BAC) of 1‰. Blood samples were taken before alcohol drinking as a control, and after 2, 4, 6, 24 and 48 h after beginning with alcohol consumption. In addition, urine samples were collected. Intestinal permeability was determined by serum and urine values of FABP-I, syndecan-1, and soluble (s)CD14 as a marker for the endotoxin translocation via the intestinal barrier by ELISA. BAC was determined. RESULTS Systemic FABP-I was significantly reduced 2 h after the onset of alcohol drinking, and remained decreased after 4 h. However, at 6 h, FABP-I significantly elevated compared to previous measurements as well as to controls (p < 0.05). Systemic sCD14 was significantly elevated after 6, 24 and 48 h after the onset of alcohol consumption (p < 0.05). Systemic FABP-I at 2 h after drinking significantly correlated with the sCD14 concentration after 24 h indicating an enhanced systemic LPS bioactivity. Women showed significantly lower levels of syndecan-1 in serum and urine and urine for all time points until 6 h and lower FABP-I in the serum after 2 h. CONCLUSIONS Even relative low amounts of alcohol affect the immune system of healthy volunteers, although these changes appear minor in women. A potential damage to the intestinal barrier and presumed enhanced systemic endotoxin bioactivity after acute alcohol consumption is proposed, which represents a continuous immunological challenge for the organism and should be considered for the following days after drinking.
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Affiliation(s)
- Ramona Sturm
- Department of Trauma, Hand and Reconstructive Surgery, Goethe University, Frankfurt, Germany
| | - Florian Haag
- Department of Trauma, Hand and Reconstructive Surgery, Goethe University, Frankfurt, Germany
- Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto Von Guericke University, Magdeburg, Germany
| | - Andrea Janicova
- Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto Von Guericke University, Magdeburg, Germany
| | - Baolin Xu
- Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto Von Guericke University, Magdeburg, Germany
| | - Jan Tilmann Vollrath
- Department of Trauma, Hand and Reconstructive Surgery, Goethe University, Frankfurt, Germany
| | | | - Ildiko Rita Dunay
- Institute of Inflammation and Neurodegeneration, Otto Von Guericke University, Magdeburg, Germany
| | | | - Ingo Marzi
- Department of Trauma, Hand and Reconstructive Surgery, Goethe University, Frankfurt, Germany
| | - Borna Relja
- Department of Trauma, Hand and Reconstructive Surgery, Goethe University, Frankfurt, Germany.
- Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto Von Guericke University, Magdeburg, Germany.
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11
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Colonic perforation following major burns: Experience from a burns center and a systematic review. Burns 2021; 47:1241-1251. [PMID: 33980400 DOI: 10.1016/j.burns.2021.04.018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 04/07/2021] [Accepted: 04/18/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Major burns complicated by stress ulceration and perforation of the stomach or duodenum is a recognized clinical phenomenon. Colonic perforation in burns patients is not common, and the overall incidence, diagnosis, intervention undertaken and mortality is incompletely described in the literature. METHOD We performed a systematic review of the literature on severe burns resulting in colonic perforation during the initial admission period. Relevant studies from January 1975 to June 2020 were retrieved from MEDLINE and EMBASE databases. Patient demographics, co-morbidities, total body surface area (TBSA) and anatomical region of burn, site of colonic perforation and management, nutrition, sepsis and microbiology, length of stay and overall outcome were extracted. We present a case series of five burns patients who had colonic perforations in our Specialist Burns Center. RESULTS We identified 54 studies, of which nine (two case series and seven case reports) met the inclusion criteria. Colonic perforation following burns was most common in middle-aged male patients with a proportion of patients having a history of mental health issues. In most cases, the TBSA associated with a colonic perforation was ≥30% (11/16 patients, 69%). Perforations mainly affected the right side of the colon (12/16 patients, 75%), usually occurring after the second week of admission (13/16 patients, 81%). Right-sided colonic perforations were associated with an increased mortality rate compared to left-sided perforations (42% vs 25%). CONCLUSIONS The current literature is mainly limited to case series and case reports and confirms that colonic perforations in burns patients are rare. Colonic perforations are related to the systemic effect of burn injuries including sepsis and gastrointestinal stasis. We have identified patients who are at higher risk of developing colonic perforations and have described the common findings in these patients. Through greater awareness early diagnosis and prompt intervention may be achieved to improve outcomes and reduce associated morbidity and mortality.
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12
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Power N, Turpin W, Espin-Garcia O, Smith MI, Croitoru K. Serum Zonulin Measured by Commercial Kit Fails to Correlate With Physiologic Measures of Altered Gut Permeability in First Degree Relatives of Crohn's Disease Patients. Front Physiol 2021; 12:645303. [PMID: 33841181 PMCID: PMC8027468 DOI: 10.3389/fphys.2021.645303] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 02/26/2021] [Indexed: 12/22/2022] Open
Abstract
Intestinal epithelial cell tight junctions (TJs) contribute to the integrity of the intestinal barrier allowing for control of the physical barrier between external antigens or bacterial products and the internal environment. Zonula occludens-1 (ZO-1) is a protein that modulates intestinal TJs, and serum levels of ZO-1 has been suggested as a biomarker of disrupted barrier function in humans. Previous studies suggested that increased intestinal permeability was associated with evidence of TJ abnormalities. However, there is limited information on the serological measurement of ZO-1 and its relation to other tests of barrier function in healthy subjects. We investigated the correlation of serum ZO-1, with physiologic measures of intestinal permeability (as the ratio of the fractional excretion of lactulose-mannitol or LMR) in a cohort of 39 healthy FDRs of Crohn's disease (CD) patients. No significant correlation was found between LMR and ZO-1 levels (r2 = 0.004, P < 0.71), or intestinal fatty acid binding proteins (I-FABP) (r2 = 0.004, P < 0.71). In conclusion, our data show that ZO-1 and I-FABP are not a marker of gut permeability as defined by LMR.
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Affiliation(s)
- Namita Power
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, ON, Canada.,Department of Gastroenterology, Lunenfeld-Tanenbaum Research Institute, Toronto, ON, Canada
| | - Williams Turpin
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, ON, Canada.,Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Osvaldo Espin-Garcia
- Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
| | - Michelle I Smith
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, ON, Canada.,Department of Gastroenterology, Lunenfeld-Tanenbaum Research Institute, Toronto, ON, Canada
| | | | - Kenneth Croitoru
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, ON, Canada.,Department of Gastroenterology, Lunenfeld-Tanenbaum Research Institute, Toronto, ON, Canada.,Department of Medicine, University of Toronto, Toronto, ON, Canada
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13
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Strang SG, Breederveld RS, Cleffken BI, Verhofstad MHJ, Van Waes OJF, Van Lieshout EMM. Prevalence of intra-abdominal hypertension and markers for associated complications among severe burn patients: a multicenter prospective cohort study (BURNIAH study). Eur J Trauma Emerg Surg 2021; 48:1137-1149. [PMID: 33721051 PMCID: PMC9001214 DOI: 10.1007/s00068-021-01623-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 02/10/2021] [Indexed: 10/25/2022]
Abstract
PURPOSE Severely burned patients are at risk for intra-abdominal hypertension (IAH) and associated complications such as organ failure, abdominal compartment syndrome (ACS), and death. The aim of this study was to determine the prevalence of IAH among severely burned patients. The secondary aim was to determine the value of urinary intestinal fatty acid binding protein (I-FABP) as early marker for IAH-associated complications. METHODS A prospective observational study was performed in two burn centers in the Netherlands. Fifty-eight patients with burn injuries ≥ 15% of total body surface area (TBSA) were included. Intra-abdominal pressure (IAP) and urinary I-FABP, measured every 6 h during 72 h. Prevalence of IAH, new organ failure and ACS, and the value of urinary intestinal fatty acid binding protein (I-FABP) as early marker for IAH-associated complications were determined. RESULTS Thirty-one (53%) patients developed IAH, 17 (29%) patients developed new organ failure, but no patients developed ACS. Patients had burns of 29% (P25-P75 19-42%) TBSA. Ln-transformed levels of urinary I-FABP and IAP were inversely correlated with an estimate of - 0.06 (95% CI - 0.10 to - 0.02; p = 0.002). Maximal urinary I-FABP levels had a fair discriminatory ability for patients with IAH with an area under the ROC curve of 74% (p = 0.001). Urinary I-FABP levels had no predictive value for IAH or new organ failure in severe burn patients. CONCLUSIONS The prevalence of IAH among patients with ≥ 15% TBSA burned was 53%. None of the patients developed ACS. A relevant diagnostic or predictive value of I-FABP levels in identifying patients at risk for IAH-related complications, could not be demonstrated. LEVEL OF EVIDENCE Level III, epidemiologic and diagnostic prospective observational study.
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Affiliation(s)
- Steven G Strang
- Trauma Research Unit, Department of Surgery, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands
| | - Roelf S Breederveld
- Burn Center, Red Cross Hospital, Beverwijk, The Netherlands.,Department of Surgery, Leiden University Medical Centre, Leiden, The Netherlands
| | | | - Michael H J Verhofstad
- Trauma Research Unit, Department of Surgery, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands
| | - Oscar J F Van Waes
- Trauma Research Unit, Department of Surgery, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands
| | - Esther M M Van Lieshout
- Trauma Research Unit, Department of Surgery, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
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14
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Tang ML, Li YQ, Chen X, Lin H, Jiang ZC, Gu DL, Chen X, Tang CX, Xie ZQ. Co-Infection with Common Respiratory Pathogens and SARS-CoV-2 in Patients with COVID-19 Pneumonia and Laboratory Biochemistry Findings: A Retrospective Cross-Sectional Study of 78 Patients from a Single Center in China. Med Sci Monit 2021; 27:e929783. [PMID: 33388738 PMCID: PMC7789049 DOI: 10.12659/msm.929783] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND This retrospective study aimed to investigate co-infections with common respiratory pathogens and SARS-CoV-2 and laboratory biochemistry findings in patients with COVID-19 in the Zhuzhou area of China, in order to provide a reference for the disease assessment and clinical treatment of COVID-19. MATERIAL AND METHODS The clinical data of COVID-19 patients admitted to the hospital of Zhuzhou City from January 28 to March 15, 2020, as well as laboratory test results for respiratory pathogens and biochemical indicators, were collected to conduct correlation analyses. All patients were diagnosed based on fluorescence-based PCR assay for SARS-CoV-2. RESULTS Eleven of the 78 patients (14.1%) were co-infected with other respiratory pathogens, among which Mycoplasma pneumoniae (n=5, 45.5%) and respiratory syncytial virus (n=4, 36.4%) were the most frequent. There were 8 patients co-infected with 1 other pathogen and 3 patients co-infected with 2 other pathogens. Compared with mono-infected COVID-19 patients, patients with co-infections had significantly higher levels of procalcitonin (P=0.002). CONCLUSIONS The findings showed that Mycoplasma pneumonia and respiratory syncytial virus were the most common co-infections in patients with COVID-19 pneumonia. Increased levels of PCT in patients with COVID-19 pneumonia were associated with co-infection.
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Affiliation(s)
- Man-Ling Tang
- Laboratory Medicine Center, Zhuzhou Central Hospital, Zhuzhou, Hunan, China (mainland)
| | - Yue-Qiu Li
- Department of Hepatobiliary and Pancreatic Surgery, Zhuzhou Central Hospital, Zhuzhou, Hunan, China (mainland)
| | - Xiang Chen
- Laboratory Medicine Center, Zhuzhou Central Hospital, Zhuzhou, Hunan, China (mainland)
| | - Hui Lin
- Laboratory Medicine Center, Zhuzhou Central Hospital, Zhuzhou, Hunan, China (mainland)
| | - Zhong-Chun Jiang
- Department of Hepatobiliary and Pancreatic Surgery, Zhuzhou Central Hospital, Zhuzhou, Hunan, China (mainland)
| | - Dai-Li Gu
- Department of Hepatobiliary and Pancreatic Surgery, Zhuzhou Central Hospital, Zhuzhou, Hunan, China (mainland)
| | - Xun Chen
- Department of Hepatobiliary and Pancreatic Surgery, Zhuzhou Central Hospital, Zhuzhou, Hunan, China (mainland)
| | - Cai-Xi Tang
- Department of Hepatobiliary and Pancreatic Surgery, Zhuzhou Central Hospital, Zhuzhou, Hunan, China (mainland)
| | - Zhi-Qin Xie
- Department of Hepatobiliary and Pancreatic Surgery, Zhuzhou Central Hospital, Zhuzhou, Hunan, China (mainland)
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15
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Walrath T, Dyamenahalli KU, Hulsebus HJ, McCullough RL, Idrovo JP, Boe DM, McMahan RH, Kovacs EJ. Age-related changes in intestinal immunity and the microbiome. J Leukoc Biol 2020; 109:1045-1061. [PMID: 33020981 DOI: 10.1002/jlb.3ri0620-405rr] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2020] [Revised: 09/11/2020] [Accepted: 09/13/2020] [Indexed: 12/19/2022] Open
Abstract
The gastrointestinal (GI) tract is a vitally important site for the adsorption of nutrients as well as the education of immune cells. Homeostasis of the gut is maintained by the interplay of the intestinal epithelium, immune cells, luminal Ags, and the intestinal microbiota. The well-being of the gut is intrinsically linked to the overall health of the host, and perturbations to this homeostasis can have severe impacts on local and systemic health. One factor that causes disruptions in gut homeostasis is age, and recent research has elucidated how critical systems within the gut are altered during the aging process. Intestinal stem cell proliferation, epithelial barrier function, the gut microbiota, and the composition of innate and adaptive immune responses are all altered in advanced age. The aging population continues to expand worldwide, a phenomenon referred to as the "Silver Tsunami," and every effort must be made to understand how best to prevent and treat age-related maladies. Here, recent research about changes observed in the intestinal epithelium, the intestinal immune system, the microbiota, and how the aging gut interacts with and influences other organs such as the liver, lung, and brain are reviewed. Better understanding of these age-related changes and their impact on multi-organ interactions will aid the development of therapies to increase the quality of life for all aged individuals.
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Affiliation(s)
- Travis Walrath
- Department of Surgery, Division of GI, Trauma and Endocrine Surgery, and Burn Research Program, University of Colorado Denver, Aurora, Colorado, USA
| | - Kiran U Dyamenahalli
- Department of Surgery, Division of GI, Trauma and Endocrine Surgery, and Burn Research Program, University of Colorado Denver, Aurora, Colorado, USA
| | - Holly J Hulsebus
- Department of Surgery, Division of GI, Trauma and Endocrine Surgery, and Burn Research Program, University of Colorado Denver, Aurora, Colorado, USA.,Immunology Graduate Program, University of Colorado Denver, Aurora, Colorado, USA
| | - Rebecca L McCullough
- Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, Colorado, USA.,GI and Liver Innate Immune Program, University of Colorado Denver, Aurora, Colorado, USA
| | - Juan-Pablo Idrovo
- Department of Surgery, Division of GI, Trauma and Endocrine Surgery, and Burn Research Program, University of Colorado Denver, Aurora, Colorado, USA
| | - Devin M Boe
- Department of Surgery, Division of GI, Trauma and Endocrine Surgery, and Burn Research Program, University of Colorado Denver, Aurora, Colorado, USA.,Immunology Graduate Program, University of Colorado Denver, Aurora, Colorado, USA.,Medical Scientist Training Program, University of Colorado Denver, Aurora, Colorado, USA
| | - Rachel H McMahan
- Department of Surgery, Division of GI, Trauma and Endocrine Surgery, and Burn Research Program, University of Colorado Denver, Aurora, Colorado, USA
| | - Elizabeth J Kovacs
- Department of Surgery, Division of GI, Trauma and Endocrine Surgery, and Burn Research Program, University of Colorado Denver, Aurora, Colorado, USA.,Immunology Graduate Program, University of Colorado Denver, Aurora, Colorado, USA.,Medical Scientist Training Program, University of Colorado Denver, Aurora, Colorado, USA.,GI and Liver Innate Immune Program, University of Colorado Denver, Aurora, Colorado, USA
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16
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Chikina AS, Nadalin F, Maurin M, San-Roman M, Thomas-Bonafos T, Li XV, Lameiras S, Baulande S, Henri S, Malissen B, Lacerda Mariano L, Barbazan J, Blander JM, Iliev ID, Matic Vignjevic D, Lennon-Duménil AM. Macrophages Maintain Epithelium Integrity by Limiting Fungal Product Absorption. Cell 2020; 183:411-428.e16. [PMID: 32970988 PMCID: PMC7646275 DOI: 10.1016/j.cell.2020.08.048] [Citation(s) in RCA: 86] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Revised: 07/27/2020] [Accepted: 08/26/2020] [Indexed: 12/14/2022]
Abstract
The colon is primarily responsible for absorbing fluids. It contains a large number of microorganisms including fungi, which are enriched in its distal segment. The colonic mucosa must therefore tightly regulate fluid influx to control absorption of fungal metabolites, which can be toxic to epithelial cells and lead to barrier dysfunction. How this is achieved remains unknown. Here, we describe a mechanism by which the innate immune system allows rapid quality check of absorbed fluids to avoid intoxication of colonocytes. This mechanism relies on a population of distal colon macrophages that are equipped with "balloon-like" protrusions (BLPs) inserted in the epithelium, which sample absorbed fluids. In the absence of macrophages or BLPs, epithelial cells keep absorbing fluids containing fungal products, leading to their death and subsequent loss of epithelial barrier integrity. These results reveal an unexpected and essential role of macrophages in the maintenance of colon-microbiota interactions in homeostasis. VIDEO ABSTRACT.
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Affiliation(s)
- Aleksandra S Chikina
- Institut Curie, PSL Research University, CNRS UMR 144, F-75005 Paris, France; Institut Curie, PSL Research University, INSERM U932, F-75005 Paris, France
| | - Francesca Nadalin
- Institut Curie, PSL Research University, INSERM U932, F-75005 Paris, France
| | - Mathieu Maurin
- Institut Curie, PSL Research University, INSERM U932, F-75005 Paris, France
| | - Mabel San-Roman
- Institut Curie, PSL Research University, INSERM U932, F-75005 Paris, France
| | | | - Xin V Li
- Gastroenterology and Hepatology Division, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA
| | - Sonia Lameiras
- Institut Curie, PSL Research University, Next Generation Sequencing Facility, F-75005 Paris, France
| | - Sylvain Baulande
- Institut Curie, PSL Research University, Next Generation Sequencing Facility, F-75005 Paris, France
| | - Sandrine Henri
- Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, 13288 Marseille, France
| | - Bernard Malissen
- Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, 13288 Marseille, France; Centre d'Immunophénomique, Aix Marseille Université, INSERM, CNRS, 13288 Marseille, France
| | | | - Jorge Barbazan
- Institut Curie, PSL Research University, CNRS UMR 144, F-75005 Paris, France
| | - J Magarian Blander
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA
| | - Iliyan D Iliev
- Gastroenterology and Hepatology Division, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA
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17
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Strang SG, Habes QLM, Van der Hoven B, Tuinebreijer WE, Verhofstad MHJ, Pickkers P, Van Lieshout EMM, Van Waes OJF. Intestinal fatty acid binding protein as a predictor for intra-abdominal pressure-related complications in patients admitted to the intensive care unit; a prospective cohort study (I-Fabulous study). J Crit Care 2020; 63:211-217. [PMID: 32980233 DOI: 10.1016/j.jcrc.2020.08.023] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 08/24/2020] [Accepted: 08/30/2020] [Indexed: 11/16/2022]
Abstract
PURPOSE Critically ill patients are at risk for intra-abdominal hypertension (IAH) and related complications such as organ failure, abdominal compartment syndrome (ACS), and death. This study aimed to determine the value of urinary and serum intestinal fatty acid binding protein (I-FABP) levels as early marker for IAH-associated complications. METHODS A prospective observational study was conducted in two academic institutional mixed medical-surgical ICUs in the Netherlands. Adult patients admitted to the ICU with two or more risk factors for IAH (198) were included. Urinary and serum I-FABP and intra-abdominal pressure (IAP) were measured every six hours during 72 h. RESULTS Fifteen (8%) patients developed ACS and 74 (37%) developed new organ failure. I-FABP and IAP were positively correlated. Patients who developed ACS had higher median baseline levels of urinary I-FABP (235(P25-P75 85-1747)μg/g creat) than patients with IAH who did not develop ACS (87(P25-P75 33-246)μg/g, p = 0.037). With an odds ratio of 1.00, neither urinary nor serum I-FABP indicated increased risk for developing new organ failure or ACS. CONCLUSIONS A relevant diagnostic value of I-FABP levels for identifying individual patients at risk for intra-abdominal pressure related complications could not be demonstrated.
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Affiliation(s)
- Steven G Strang
- Trauma Research Unit, Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Quirine L M Habes
- Department of Intensive Care Medicine, Radboudumc, Nijmegen, the Netherlands
| | - Ben Van der Hoven
- Department of Intensive Care Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Wim E Tuinebreijer
- Trauma Research Unit, Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Michael H J Verhofstad
- Trauma Research Unit, Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Peter Pickkers
- Department of Intensive Care Medicine, Radboudumc, Nijmegen, the Netherlands
| | - Esther M M Van Lieshout
- Trauma Research Unit, Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
| | - Oscar J F Van Waes
- Trauma Research Unit, Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
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18
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Intestinal permeability in participants with thermal injury: A case series from a prospective, longitudinal study (HESTIA). BURNS OPEN 2020. [DOI: 10.1016/j.burnso.2020.05.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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19
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Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium through Activation of the Sweet Taste Receptor, T1R3. Nutrients 2020; 12:nu12061862. [PMID: 32580504 PMCID: PMC7353258 DOI: 10.3390/nu12061862] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 06/18/2020] [Accepted: 06/20/2020] [Indexed: 12/20/2022] Open
Abstract
The breakdown of the intestinal epithelial barrier and subsequent increase in intestinal permeability can lead to systemic inflammatory diseases and multiple-organ failure. Nutrition impacts the intestinal barrier, with dietary components such as gluten increasing permeability. Artificial sweeteners are increasingly consumed by the general public in a range of foods and drinks. The sweet taste receptor (T1R3) is activated by artificial sweeteners and has been identified in the intestine to play a role in incretin release and glucose transport; however, T1R3 has not been previously linked to intestinal permeability. Here, the intestinal epithelial cell line, Caco-2, was used to study the effect of commonly-consumed artificial sweeteners, sucralose, aspartame and saccharin, on permeability. At high concentrations, aspartame and saccharin were found to induce apoptosis and cell death in intestinal epithelial cells, while at low concentrations, sucralose and aspartame increased epithelial barrier permeability and down-regulated claudin 3 at the cell surface. T1R3 knockdown was found to attenuate these effects of artificial sweeteners. Aspartame induced reactive oxygen species (ROS) production to cause permeability and claudin 3 internalization, while sweetener-induced permeability and oxidative stress was rescued by the overexpression of claudin 3. Taken together, our findings demonstrate that the artificial sweeteners sucralose, aspartame, and saccharin exert a range of negative effects on the intestinal epithelium through the sweet taste receptor T1R3.
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20
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Novakovic M, Rout A, Kingsley T, Kirchoff R, Singh A, Verma V, Kant R, Chaudhary R. Role of gut microbiota in cardiovascular diseases. World J Cardiol 2020; 12:110-122. [PMID: 32431782 PMCID: PMC7215967 DOI: 10.4330/wjc.v12.i4.110] [Citation(s) in RCA: 110] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2019] [Revised: 03/03/2020] [Accepted: 03/12/2020] [Indexed: 02/06/2023] Open
Abstract
The human gut is colonized by a community of microbiota, primarily bacteria, that exist in a symbiotic relationship with the host. Intestinal microbiota-host interactions play a critical role in the regulation of human physiology. Deleterious changes to the composition of gut microbiota, referred to as gut dysbiosis, has been linked to the development and progression of numerous diseases, including cardiovascular disease (CVD). Imbalances in host-microbial interaction impair homeostatic mechanisms that regulate health and can activate multiple pathways leading to CVD risk factor progression. Most CVD risk factors, including aging, obesity, dietary patterns, and a sedentary lifestyle, have been shown to induce gut dysbiosis. Dysbiosis is associated with intestinal inflammation and reduced integrity of the gut barrier, which in turn increases circulating levels of bacterial structural components and microbial metabolites, including trimethylamine-N-oxide and short-chain fatty acids, that may facilitate the development of CVD. This article reviews the normal function and composition of the gut microbiome, mechanisms leading to the leaky gut syndrome, its mechanistic link to CVD and potential novel therapeutic approaches aimed towards restoring gut microbiome and CVD prevention. As CVD is the leading cause of deaths globally, investigating the gut microbiota as a locus of intervention presents a novel and clinically relevant avenue for future research.
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Affiliation(s)
- Marko Novakovic
- Department of Internal Medicine, Sinai Hospital of Baltimore, Baltimore, MD 21215, United States
| | - Amit Rout
- Department of Internal Medicine, Sinai Hospital of Baltimore, Baltimore, MD 21215, United States
| | - Thomas Kingsley
- Department of Internal Medicine, Division of Hospital Internal Medicine, Mayo Clinic, Rochester, MN 55905, United States
| | - Robert Kirchoff
- Department of Internal Medicine, Division of Hospital Internal Medicine, Mayo Clinic, Rochester, MN 55905, United States
| | - Amteshwar Singh
- Department of Internal Medicine, Division of Hospital Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
| | - Vipin Verma
- Department of Internal Medicine, Medical University of South Carolina/AnMed Campus, Charleston, SC 29425, United States
| | - Ravi Kant
- Division of Endocrinology, Diabetes and Nutrition, Medical University of South Carolina/Anmed Campus, Anderson, SC 29621, United States
| | - Rahul Chaudhary
- Department of Internal Medicine, Division of Hospital Internal Medicine, Mayo Clinic, Rochester, MN 55905, United States.
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21
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Voth M, Lustenberger T, Relja B, Marzi I. Is I-FABP not only a marker for the detection abdominal injury but also of hemorrhagic shock in severely injured trauma patients? World J Emerg Surg 2019; 14:49. [PMID: 31832083 PMCID: PMC6868704 DOI: 10.1186/s13017-019-0267-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Accepted: 09/26/2019] [Indexed: 12/18/2022] Open
Abstract
Background Hemorrhagic shock can lead to intestinal damage with subsequent hyperinflammation and multiple organ dysfunction syndrome (MODS). The intestinal fatty acid-binding protein (I-FABP) is solely expressed in the intestine and is released extracellulary after tissue damage. This study evaluates the validity of I-FABP as an early biomarker to detect hemorrhagic shock and abdominal injury. Patients and methods Severely injured patients with an Injury Severity Score (ISS) ≥ 16 points and an age ≥ 18 years, admitted from January 2010 to December 2016, were included. Overall, 26 patients retrospectively presented with hemorrhagic shock to the emergency room (ER): 8 patients without abdominal injury ("HS noAbd") and 18 patients with abdominal injury ("HS Abd"). Furthermore, 16 severely injured patients without hemorrhagic shock and without abdominal injury ("noHS noAbd") were retrospectively selected as controls. Plasma I-FABP levels were measured at admission to the ER and up to 3 days posttraumatic (d1-d3). Results Median I-FABP levels were significantly higher in the "HS Abd" group compared with the "HS noAbd" group (28,637.0 pg/ml [IQR = 6372.4-55,550.0] vs. 7292.3 pg/ml [IQR = 1282.5-11,159.5], p < 0.05). Furthermore, I-FABP levels of both hemorrhagic shock groups were significantly higher compared with the "noHS noAbd" group (844.4 pg/ml [IQR = 530.0-1432.9], p < 0.05). The time course of I-FABP levels showed a peak on the day of admission with a subsequent decline in the post-traumatic course. Furthermore, significant correlations between I-FABP levels and clinical parameters of hemorrhagic shock, such as hemoglobin, lactate value, systolic blood pressure (SBP), and shock index, were found.The optimal cut-off level of I-FABP for detection of hemorrhagic shock was 1761.9 pg/ml with a sensitivity of 85% and a specificity of 81%. Conclusion This study confirmed our previous observation that I-FABP might be used as a suitable early biomarker for the detection of abdominal injuries in general. In addition, I-FABP may also be a useful and a promising parameter in the diagnosis of hemorrhagic shock, because of reflecting low intestinal perfusion.
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Affiliation(s)
- Maika Voth
- Department of Trauma, Hand and Reconstructive Surgery, University Hospital, Goethe University Frankfurt, Theodor-Stern-Kai 7, D-60590 Frankfurt, Main, Germany
| | - Thomas Lustenberger
- Department of Trauma, Hand and Reconstructive Surgery, University Hospital, Goethe University Frankfurt, Theodor-Stern-Kai 7, D-60590 Frankfurt, Main, Germany
| | - Borna Relja
- Department of Trauma, Hand and Reconstructive Surgery, University Hospital, Goethe University Frankfurt, Theodor-Stern-Kai 7, D-60590 Frankfurt, Main, Germany
| | - Ingo Marzi
- Department of Trauma, Hand and Reconstructive Surgery, University Hospital, Goethe University Frankfurt, Theodor-Stern-Kai 7, D-60590 Frankfurt, Main, Germany
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22
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Elke G, Hartl WH, Kreymann KG, Adolph M, Felbinger TW, Graf T, de Heer G, Heller AR, Kampa U, Mayer K, Muhl E, Niemann B, Rümelin A, Steiner S, Stoppe C, Weimann A, Bischoff SC. Clinical Nutrition in Critical Care Medicine - Guideline of the German Society for Nutritional Medicine (DGEM). Clin Nutr ESPEN 2019; 33:220-275. [PMID: 31451265 DOI: 10.1016/j.clnesp.2019.05.002] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Accepted: 05/03/2019] [Indexed: 02/07/2023]
Abstract
PURPOSE Enteral and parenteral nutrition of adult critically ill patients varies in terms of the route of nutrient delivery, the amount and composition of macro- and micronutrients, and the choice of specific, immune-modulating substrates. Variations of clinical nutrition may affect clinical outcomes. The present guideline provides clinicians with updated consensus-based recommendations for clinical nutrition in adult critically ill patients who suffer from at least one acute organ dysfunction requiring specific drug therapy and/or a mechanical support device (e.g., mechanical ventilation) to maintain organ function. METHODS The former guidelines of the German Society for Nutritional Medicine (DGEM) were updated according to the current instructions of the Association of the Scientific Medical Societies in Germany (AWMF) valid for a S2k-guideline. According to the S2k-guideline classification, no systematic review of the available evidence was required to make recommendations, which, therefore, do not state evidence- or recommendation grades. Nevertheless, we considered and commented the evidence from randomized-controlled trials, meta-analyses and observational studies with adequate sample size and high methodological quality (until May 2018) as well as from currently valid guidelines of other societies. The liability of each recommendation was described linguistically. Each recommendation was finally validated and consented through a Delphi process. RESULTS In the introduction the guideline describes a) the pathophysiological consequences of critical illness possibly affecting metabolism and nutrition of critically ill patients, b) potential definitions for different disease phases during the course of illness, and c) methodological shortcomings of clinical trials on nutrition. Then, we make 69 consented recommendations for essential, practice-relevant elements of clinical nutrition in critically ill patients. Among others, recommendations include the assessment of nutrition status, the indication for clinical nutrition, the timing and route of nutrient delivery, and the amount and composition of substrates (macro- and micronutrients); furthermore, we discuss distinctive aspects of nutrition therapy in obese critically ill patients and those treated with extracorporeal support devices. CONCLUSION The current guideline provides clinicians with up-to-date recommendations for enteral and parenteral nutrition of adult critically ill patients who suffer from at least one acute organ dysfunction requiring specific drug therapy and/or a mechanical support device (e.g., mechanical ventilation) to maintain organ function. The period of validity of the guideline is approximately fixed at five years (2018-2023).
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Affiliation(s)
- Gunnar Elke
- Department of Anesthesiology and Intensive Care Medicine, University Medical Center Schleswig-Holstein, Campus Kiel, Arnold-Heller-Str. 3, Haus 12, 24105, Kiel, Germany.
| | - Wolfgang H Hartl
- Department of Surgery, University School of Medicine, Grosshadern Campus, Ludwig-Maximilian University, Marchioninistr. 15, 81377 Munich, Germany.
| | | | - Michael Adolph
- University Department of Anesthesiology and Intensive Care Medicine, University Hospital Tübingen, Hoppe-Seyler-Straße 3, 72076, Tübingen, Germany.
| | - Thomas W Felbinger
- Department of Anesthesiology, Critical Care and Pain Medicine, Neuperlach and Harlaching Medical Center, The Munich Municipal Hospitals Ltd, Oskar-Maria-Graf-Ring 51, 81737, Munich, Germany.
| | - Tobias Graf
- Medical Clinic II, University Heart Center Lübeck, University Medical Center Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.
| | - Geraldine de Heer
- Center for Anesthesiology and Intensive Care Medicine, Clinic for Intensive Care Medicine, University Hospital Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
| | - Axel R Heller
- Clinic for Anesthesiology and Surgical Intensive Care Medicine, University of Augsburg, Stenglinstrasse 2, 86156, Augsburg, Germany.
| | - Ulrich Kampa
- Clinic for Anesthesiology, Lutheran Hospital Hattingen, Bredenscheider Strasse 54, 45525, Hattingen, Germany.
| | - Konstantin Mayer
- Department of Internal Medicine, Justus-Liebig University Giessen, University of Giessen and Marburg Lung Center, Klinikstr. 36, 35392, Gießen, Germany.
| | - Elke Muhl
- Eichhörnchenweg 7, 23627, Gross Grönau, Germany.
| | - Bernd Niemann
- Department of Adult and Pediatric Cardiovascular Surgery, Giessen University Hospital, Rudolf-Buchheim-Str. 7, 35392, Gießen, Germany.
| | - Andreas Rümelin
- Clinic for Anesthesia and Surgical Intensive Care Medicine, HELIOS St. Elisabeth Hospital Bad Kissingen, Kissinger Straße 150, 97688, Bad Kissingen, Germany.
| | - Stephan Steiner
- Department of Cardiology, Pneumology and Intensive Care Medicine, St Vincenz Hospital Limburg, Auf dem Schafsberg, 65549, Limburg, Germany.
| | - Christian Stoppe
- Department of Intensive Care Medicine and Intermediate Care, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany.
| | - Arved Weimann
- Department of General, Visceral and Oncological Surgery, Klinikum St. Georg, Delitzscher Straße 141, 04129, Leipzig, Germany.
| | - Stephan C Bischoff
- Department for Nutritional Medicine, University of Hohenheim, Fruwirthstr. 12, 70599, Stuttgart, Germany.
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Okada K, Sekino M, Funaoka H, Sato S, Ichinomiya T, Murata H, Maekawa T, Nishikido M, Eishi K, Hara T. Intestinal fatty acid-binding protein levels in patients with chronic renal failure. J Surg Res 2018; 230:94-100. [PMID: 30100046 DOI: 10.1016/j.jss.2018.04.057] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Revised: 03/30/2018] [Accepted: 04/24/2018] [Indexed: 01/15/2023]
Abstract
BACKGROUND Intestinal fatty acid-binding protein (I-FABP), a biomarker of enterocyte injury, has been reported to be a diagnostic marker of intestinal ischemia and a prognostic marker in critically ill patients. However, the kinetics of I-FABP in renal failure patients is unknown. We sought to identify I-FABP levels in patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD) on hemodialysis (HD) and to identify the manner in which the I-FABP levels change. MATERIALS AND METHODS Adult patients who were admitted for elective cardiac surgery with either normal renal function (NRF), CKD, or ESKD on HD were enrolled. Serum I-FABP levels in NRF and CKD patients and in ESKD patients before and after HD were determined. RESULTS A total of 124 patients were evaluated: 47 NRF, 53 CKD, and 24 ESKD. The I-FABP levels of the CKD patients and pre-HD ESKD patients were significantly higher than those of the NRF patients (P = 0.018 and P <0.001, respectively). I-FABP levels were significantly negatively correlated with the estimated glomerular filtration rate in NRF and CKD patients (Spearman's ρ = -0.313, P = 0.002). In addition, I-FABP levels in ESKD patients were significantly lower after HD than those before HD (P <0.001). CONCLUSIONS I-FABP levels in CKD and pre-HD ESKD patients were significantly higher than those in NRF patients. In addition, I-FABP was significantly eliminated by HD in patients with ESKD. Clinicians and researchers should consider this aspect of I-FABP when using it as a diagnostic and prognostic marker in patients with renal insufficiency.
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Affiliation(s)
- Kyoko Okada
- Department of Anesthesiology, Nagasaki University Hospital, Nagasaki, Japan; Department of Anesthesiology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Motohiro Sekino
- Division of Intensive Care, Nagasaki University Hospital, Nagasaki, Japan.
| | | | - Shuntaro Sato
- Clinical Research Center, Nagasaki University Hospital, Nagasaki, Japan
| | - Taiga Ichinomiya
- Department of Anesthesiology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Hiroaki Murata
- Department of Anesthesiology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Takuji Maekawa
- Department of Anesthesiology, Nagasaki University Hospital, Nagasaki, Japan
| | - Masaharu Nishikido
- Department of Urology, National Hospital Organization Nagasaki Medical Center, Nagasaki, Japan
| | - Kiyoyuki Eishi
- Department of Cardiovascular Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Tetsuya Hara
- Department of Anesthesiology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
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24
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Schellekens DHSM, Hundscheid IHR, Leenarts CAJI, Grootjans J, Lenaerts K, Buurman WA, Dejong CHC, Derikx JPM. Human small intestine is capable of restoring barrier function after short ischemic periods. World J Gastroenterol 2017; 23:8452-8464. [PMID: 29358855 PMCID: PMC5752707 DOI: 10.3748/wjg.v23.i48.8452] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2017] [Revised: 08/08/2017] [Accepted: 08/15/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To assess intestinal barrier function during human intestinal ischemia and reperfusion (IR).
METHODS In a human experimental model, 6 cm of jejunum was selectively exposed to 30 min of ischemia (I) followed by 30 and 120 min of reperfusion (R). A sham procedure was also performed. Blood and tissue was sampled at all-time points. Functional barrier function was assessed using dual-sugar absorption tests with lactulose (L) and rhamnose (R). Plasma concentrations of citrulline, an amino acid described as marker for enterocyte function were measured as marker of metabolic enterocytes restoration. Damage to the epithelial lining was assessed by immunohistochemistry for tight junctions (TJs), by plasma marker for enterocytes damage (I-FABP) and analyzed by electron microscopy (EM) using lanthanum nitrate as an electrondense marker.
RESULTS Plasma L/R ratio’s were significantly increased after 30 min of ischemia (30I) followed by 30 min of reperfusion (30R) compared to control (0.75 ± 0.10 vs 0.20 ± 0.09, P < 0.05). At 120 min of reperfusion (120R), ratio’s normalized (0.17 ± 0.06) and were not significantly different from control. Plasma levels of I-FABP correlated with plasma L/R ratios measured at the same time points (correlation: 0.467, P < 0.01). TJs staining shows distortion of staining at 30I. An intact lining of TJs was again observed at 30I120R. Electron microscopy analysis revealed disrupted TJs after 30I with paracellular leakage of lanthanum nitrate, which restored after 30I120R. Furthermore, citrulline concentrations closely paralleled the histological perturbations during intestinal IR.
CONCLUSION This study directly correlates histological data with intestinal permeability tests, revealing that the human gut has the ability of to withstand short episodes of ischemia, with morphological and functional recovery of the intestinal barrier within 120 min of reperfusion.
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Affiliation(s)
- Dirk HSM Schellekens
- Department of Surgery, Maastricht University Medical Center, Maastricht 6200 MD, the Netherlands
- NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht 6200 MD, the Netherlands
| | - Inca HR Hundscheid
- Department of Surgery, Maastricht University Medical Center, Maastricht 6200 MD, the Netherlands
- NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht 6200 MD, the Netherlands
| | - Claire AJI Leenarts
- Department of Surgery, Maastricht University Medical Center, Maastricht 6200 MD, the Netherlands
- NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht 6200 MD, the Netherlands
| | - Joep Grootjans
- NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht 6200 MD, the Netherlands
- Department of Gastroenterology, Academic Medical Center, Amsterdam 1105 AZ, the Netherlands
| | - Kaatje Lenaerts
- Department of Surgery, Maastricht University Medical Center, Maastricht 6200 MD, the Netherlands
- NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht 6200 MD, the Netherlands
| | - Wim A Buurman
- NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht 6200 MD, the Netherlands
- MHeNs School of Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht 6200 MD, the Netherlands
| | - Cornelis HC Dejong
- Department of Surgery, Maastricht University Medical Center, Maastricht 6200 MD, the Netherlands
- NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht 6200 MD, the Netherlands
| | - Joep PM Derikx
- Department of Surgery, Maastricht University Medical Center, Maastricht 6200 MD, the Netherlands
- NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht 6200 MD, the Netherlands
- Pediatric Surgical Center of Amsterdam, Emma Children's Hospital Academic Medical Center and VU University Medical Center, Amsterdam 1100 DE, the Netherlands
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25
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Cummins G, Yung DE, Cox BF, Koulaouzidis A, Desmulliez MPY, Cochran S. Luminally expressed gastrointestinal biomarkers. Expert Rev Gastroenterol Hepatol 2017; 11:1119-1134. [PMID: 28849686 DOI: 10.1080/17474124.2017.1373017] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
A biomarker is a measurable indicator of normal biologic processes, pathogenic processes or pharmacological responses. The identification of a useful biomarker is challenging, with several hurdles to overcome before clinical adoption. This review gives a general overview of a range of biomarkers associated with inflammatory bowel disease or colorectal cancer along the gastrointestinal tract. Areas covered: These markers include those that are already clinically accepted, such as inflammatory markers such as faecal calprotectin, S100A12 (Calgranulin C), Fatty Acid Binding Proteins (FABP), malignancy markers such as Faecal Occult Blood, Mucins, Stool DNA, Faecal microRNA (miRNA), other markers such as Faecal Elastase, Faecal alpha-1-antitrypsin, Alpha2-macroglobulin and possible future markers such as microbiota, volatile organic compounds and pH. Expert commentary: There are currently a few biomarkers that have been sufficiently validated for routine clinical use at present such as FC. However, many of these biomarkers continue to be limited in sensitivity and specificity for various GI diseases. Emerging biomarkers have the potential to improve diagnosis and monitoring but further study is required to determine efficacy and validate clinical utility.
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Affiliation(s)
- Gerard Cummins
- a Institute of Sensors, Signals and Systems, School of Engineering and Physical Sciences , Heriot-Watt University , Edinburgh , UK
| | - Diana E Yung
- b The Royal Infirmary of Edinburgh , Endoscopy Unit , Edinburgh , UK
| | - Ben F Cox
- c School of Medicine , University of Dundee , Dundee , UK
| | | | - Marc P Y Desmulliez
- a Institute of Sensors, Signals and Systems, School of Engineering and Physical Sciences , Heriot-Watt University , Edinburgh , UK
| | - Sandy Cochran
- d Medical and Industrial Ultrasonics, School of Engineering , University of Glasgow , Glasgow , UK
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26
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Sekino M, Funaoka H, Sato S, Okada K, Inoue H, Yano R, Matsumoto S, Ichinomiya T, Higashijima U, Matsumoto S, Hara T. Intestinal fatty acid-binding protein level as a predictor of 28-day mortality and bowel ischemia in patients with septic shock: A preliminary study. J Crit Care 2017; 42:92-100. [PMID: 28710988 DOI: 10.1016/j.jcrc.2017.07.012] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2017] [Revised: 06/30/2017] [Accepted: 07/06/2017] [Indexed: 02/06/2023]
Abstract
PURPOSE We sought to evaluate the levels of intestinal fatty acid-binding protein (I-FABP), a biomarker of enterocyte injury, as a predictor of 28-day mortality and bowel ischemia in septic shock patients. MATERIAL AND METHODS In this preliminary prospective observational study, 57 adult septic shock patients under mechanical ventilation were enrolled. Serum I-FABP levels and prognostic biomarkers were recorded upon intensive care unit (ICU) admission. RESULTS The overall 28-day mortality rate of participants was 23% (13/57). Non-survivors displayed significantly higher lactate (p=0.009), I-FABP (p=0.012), and N-terminal pro-B-type natriuretic peptide (p=0.039) levels compared to survivors. Only I-FABP was associated with 28-day mortality (odds ratio, 1.036; 95% confidence interval, 1.003-1.069; p=0.031) in a multiple logistic regression analysis adjusted for the Acute Physiology and Chronic Health Evaluation II score. When divided into low and high I-FABP groups based on the optimum cut-off value of 19.0ng/mL for predicting 28-day mortality, high-I-FABP patients had a significantly higher incidence of non-occlusive mesenteric ischemia (NOMI) (2% [1/43] vs 29% [4/14]; p=0.011). CONCLUSIONS I-FABP level at ICU admission can serve as a predictor of 28-day mortality in septic shock patients and is associated with the incidence of NOMI.
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Affiliation(s)
- Motohiro Sekino
- Division of Intensive Care, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
| | - Hiroyuki Funaoka
- DS Pharma Biomedical Co., Ltd., 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan.
| | - Shuntaro Sato
- Clinical Research Center, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
| | - Kyoko Okada
- Department of Anesthesiology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
| | - Haruka Inoue
- Division of Intensive Care, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
| | - Rintaro Yano
- Division of Intensive Care, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
| | - Sojiro Matsumoto
- Division of Intensive Care, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
| | - Taiga Ichinomiya
- Department of Anesthesiology, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
| | - Ushio Higashijima
- Division of Intensive Care, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
| | - Shuhei Matsumoto
- Division of Intensive Care, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
| | - Tetsuya Hara
- Department of Anesthesiology, Nagasaki University Graduate School of Biomedical Science, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
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27
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Matsumoto S, Sekine K, Funaoka H, Funabiki T, Shimizu M, Hayashida K, Kitano M. Early diagnosis of hollow viscus injury using intestinal fatty acid-binding protein in blunt trauma patients. Medicine (Baltimore) 2017; 96:e6187. [PMID: 28272208 PMCID: PMC5348156 DOI: 10.1097/md.0000000000006187] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
A delay in diagnosing hollow viscus injury (HVI) causes an increase in mortality and morbidity. HVI remains a challenge to diagnose, and there is no specific diagnostic biomarker for HVI. We evaluated the utility of intestinal fatty acid-binding protein (I-FABP) in diagnosing HVI in blunt trauma patients. Within a 5-year period, 93 consecutive patients with clinically suspected HVI at our trauma center were prospectively enrolled. The diagnostic performance of I-FABP for HVI was compared with that of other various parameters (physical, laboratory, and radiographic findings). HVI was diagnosed in 13 patients (14%), and non-HVI was diagnosed in 80 patients (86%). The level of I-FABP was significantly higher in patients with HVI than in those with non-HVI (P = 0.014; area under the curve, 0.71). The sensitivity, specificity, positive predictive value, and negative predictive value were 76.9%, 70.0%, 29.4%, and 94.9%, respectively (P = 0.003). However, all other biomarkers were not significantly different between the groups. Presence of extraluminal air, bowel wall thickening on computed tomography (CT), and peritonitis signs were significantly higher in patients with HVI (P < 0.05). Of 49 patients (52.7%) who had a negative I-FABP and negative peritonitis signs, none developed HVI (sensitivity, 100%; negative predictive value, 100%). This is the first study that demonstrated the diagnostic value of a biomarker for HVI. I-FABP has a higher negative predictive value compared to traditional diagnostic tests. Although the accuracy of I-FABP alone was insufficient, the combination of I-FABP and other findings can enhance diagnostic ability.
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Affiliation(s)
- Shokei Matsumoto
- Department of Trauma and Emergency Surgery, Saiseikai Yokohamashi Tobu Hospital, Yokohama, Japan
| | - Kazuhiko Sekine
- Department of Emergency Medicine, Saiseikai Central Hospital, Minato-ku, Tokyo, Japan
| | | | - Tomohiro Funabiki
- Department of Trauma and Emergency Surgery, Saiseikai Yokohamashi Tobu Hospital, Yokohama, Japan
| | - Masayuki Shimizu
- Department of Trauma and Emergency Surgery, Saiseikai Yokohamashi Tobu Hospital, Yokohama, Japan
| | - Kei Hayashida
- Department of Trauma and Emergency Surgery, Saiseikai Yokohamashi Tobu Hospital, Yokohama, Japan
| | - Mitsuhide Kitano
- Department of Trauma and Emergency Surgery, Saiseikai Yokohamashi Tobu Hospital, Yokohama, Japan
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28
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Circulating intestinal fatty acid-binding protein (I-FABP) levels in acute decompensated heart failure. Clin Biochem 2017; 50:491-495. [PMID: 28232029 DOI: 10.1016/j.clinbiochem.2017.02.014] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2017] [Revised: 02/17/2017] [Accepted: 02/18/2017] [Indexed: 01/10/2023]
Abstract
BACKGROUND Venous congestion has become increasingly recognized as a potential contributor to end-organ dysfunction in heart failure. Elevated I-FABP, which is excreted specifically from damaged intestinal epithelial cells, has been found in patients with abdominal hypertension and intestinal ischemia. We hypothesize that elevated intestinal fatty acid-binding protein (I-FABP) levels would identify patients with more advanced heart failure who have venous and intestinal congestion. METHODS Baseline serum I-FABP levels were measured in 69 acute decompensated heart failure (ADHF) patients admitted to the intensive care unit for invasive hemodynamic monitoring and tailored medical therapy. Comprehensive echocardiography examinations were performed in all study patients, and clinical outcomes (death, cardiac transplant or left ventricular assist device placement) were assessed. RESULTS The median circulating I-FABP level was 853pg/ml (interquartile range: 533 to 1448pg/ml). Age, gender, race, and baseline comorbidities were comparable between patients with low and high I-FABP levels. Although there were no significant correlations between I-FABP levels and invasively-measured hemodynamic parameters nor echocardiographic parameters, patients with higher I-FABP levels (≥853g/ml) had significantly worse clinical outcomes compared to those with lower I-FABP levels (<853pg/ml, P=0.025). CONCLUSION Circulating I-FABP levels had no association with invasively-measured hemodynamic parameters, but were associated with adverse clinical outcomes in patients with ADHF with systolic dysfunction.
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29
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Abu Faddan NH, Sherif TMK, Mohammed OA, Nasif KA, El Gezawy EM. Intestinal barrier integrity and function in infants with cholestasis. Intest Res 2017; 15:118-123. [PMID: 28239322 PMCID: PMC5323301 DOI: 10.5217/ir.2017.15.1.118] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2016] [Revised: 09/08/2016] [Accepted: 09/09/2016] [Indexed: 12/30/2022] Open
Abstract
Background/Aims The safety of the human body is maintained by effective monitoring of the mucosal surface integrity and protection against potentially harmful compounds. This function of the gut called intestinal barrier function can be affected by cholestasis and the absence of bile in the intestinal lumen. We aimed to determine whether the gut barrier integrity is impaired in infants with cholestasis by evaluation of the intestinal fatty acid binding proteins (I-FABP) and ileal bile acid binding protein (I-BABP) as markers of intestinal epithelial cell damage and plasma D-lactate level as a marker of gut wall permeability. Methods This case-control study included 53 infants with cholestasis and 29 controls. Serum levels of I-FABP, I-BABP, and D-lactate were measured in all subjects. Results Both groups of patients with neonatal hepatitis and biliary atresia showed significantly higher levels of I-FABP and I-BABP than the controls. There were no differences in the serum D-lactate level between the cases and controls. There was no difference between the two groups of patients (I and II) regarding any of the parameters studied. No significant correlations between serum levels of I-FABP, I-BABP, or D-lactate and total or direct bilirubin levels were found in the cholestatic infants. Conclusions The intestinal epithelial barrier integrity is breached nearly in all parts of the intestine in infants with cholestasis. Further research is recommended to determine the impact of this finding on the management of these infants. The relationship between physical intestinal barrier damage and its functional failure remains subject for further research.
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Affiliation(s)
- Nagla H Abu Faddan
- Department of Pediatrics, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Tahra M K Sherif
- Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Omnia A Mohammed
- Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Khalid A Nasif
- Department of Biochemistry, Faculty of Medicine, Minya University, Minya, Egypt
| | - Ebtesam M El Gezawy
- Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt
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30
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Milić L, Grigorov I, Krstić S, Ćeranić MS, Jovanović B, Stevanović J, Peško P. Serum Level of HMGB1 Protein and Inflammatory Markers in Patients with Secondary Peritonitis: Time Course and the Association with Clinical Status. J Med Biochem 2017; 36:44-53. [PMID: 28680349 PMCID: PMC5471659 DOI: 10.1515/jomb-2016-0016] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2016] [Accepted: 04/12/2016] [Indexed: 01/09/2023] Open
Abstract
Background Intra-abdominal infection in secondary peritonitis drives as excessive production of inflammatory mediators and the development of systemic inflammatory response syndrome (SIRS) or sepsis. Finding a specific marker to distinguish SIRS from sepsis would be of immense clinical importance for the therapeutic approach. It is assumed that high-mobility group box 1 protein (HMGB1) could be such a marker. In this study, we examined the time course changes in the blood levels of HMGB1, C-reactive protein (CRP), procalcitonin (PCT) and serum amyloid A (SAA) in patients with secondary peritonitis who developed SIRS or sepsis. Methods In our study, we evaluated 100 patients with diffuse secondary peritonitis who developed SIRS or sepsis (SIRS and SEPSIS group) and 30 patients with inguinal hernia as a control group. Serum levels of HMGB1, CRP, PCT, and SAA were determined on admission in all the patients, and monitored daily in patients with peritonitis until discharge from hospital. Results Preoperative HMGB1, CRP, PCT and SAA levels were statistically highly significantly increased in patients with peritonitis compared to patients with inguinal hernia, and significantly higher in patients with sepsis compared to those with SIRS. All four inflammatory markers changed significantly during the follow-up. It is interesting that the patterns of change of HMGB1 and SAA over time were distinctive for SIRS and SEPSIS groups. Conclusions HMGB1 and SAA temporal patterns might be useful in distinguishing sepsis from noninfectious SIRS in secondary peritonitis.
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Affiliation(s)
- Ljiljana Milić
- Clinic for Emergency Surgery, Emergency Center, University Clinical Center of Serbia, School of Medicine, University of Belgrade, Serbia
| | - Ilijana Grigorov
- Department of Molecular Biology, Institute for Biological Research, Belgrade, Serbia
| | - Slobodan Krstić
- Clinic for Emergency Surgery, Emergency Center, University Clinical Center of Serbia, School of Medicine, University of Belgrade, Serbia
| | - Miljan S Ćeranić
- Clinic for Digestive Surgery, University Clinical Center of Belgrade, School of Medicine, University of Belgrade, Serbia
| | - Bojan Jovanović
- Center for Anesthesiology, Emergency Center, University Clinical Center of Serbia, School of Medicine, University of Belgrade, Serbia
| | - Jelena Stevanović
- Department of Molecular Biology, Institute for Biological Research, Belgrade, Serbia
| | - Predrag Peško
- Clinic for Digestive Surgery, University Clinical Center of Belgrade, School of Medicine, University of Belgrade, Serbia
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Acute intestinal damage following severe burn correlates with the development of multiple organ dysfunction syndrome: A prospective cohort study. Burns 2016; 43:824-829. [PMID: 28040364 DOI: 10.1016/j.burns.2016.10.015] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2016] [Revised: 10/12/2016] [Accepted: 10/14/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND Severely burned patients occasionally suffer intestinal ischemia leading to a fatal outcome, and the gut is considered a "motor" driving the development of multiple organ failure. However, in clinical settings, it has been difficult to assess acute intestinal damage following burn and its consequence to patient outcome. Intestinal fatty acid binding protein (I-FABP) is a known biomarker for diagnosing intestinal ischemia/damage. This study aimed to assess the extent of intestinal damage using serial I-FABP measurements following severe burn and to clarify the association between intestinal damage and the development of organ dysfunctions. METHODS Patients aged >15years old who suffered burn over 20% total body surface area (TBSA) were enrolled in this prospective cohort study. Patients with cardiac arrest on admission or who were transferred >24h after injury were excluded. Patients with chemical burn were also excluded. Burn size and Acute Physiology and Chronic Health Evaluation II (APACHE II) score were recorded at the time of patient enrollment. I-FABP was measured on admission and at 1, 4, 7, 14, and 30days following injury. Other biomarkers such as lactate, lactate dehydrogenase (LDH), creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase, amylase, and creatinine (Cre) were also measured at the same time points as I-FABP. We also evaluated the serial change in Sequential Organ Failure Assessment (SOFA) score. RESULTS The study included 32 patients. Serum I-FABP level on the day of admission was significantly increased in the patients compared with healthy controls. Increased I-FABP levels were normalized at 4days after injury. The serum level of I-FABP on the day of admission correlated with %TBSA (III) and APACHE II score. A high I-FABP level on admission was associated with the subsequent development of multiple organ dysfunction. The increase in I-FABP level also correlated with increases of AST, LDH, and CK levels. CONCLUSIONS Serum level of I-FABP on admission day does not correlate with burn size, but with the deep burn area. The gut might be a crucial target organ following severe burn, and gut damage could have an important role in the development of multiple organ dysfunction.
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Abstract
PURPOSE OF REVIEW Gut barrier failure is associated with bacterial translocation, systemic inflammation, and is presumed to be associated with the development of multiple organ dysfunction syndrome. As the gut barrier function is carried out by a monolayer of enterocytes, a minimum requirement is the integrity of the enterocytes, and controlled paracellular permeability between adjacent enterocytes. Many factors can cause critically ill patients to lose gut barrier function by a mechanism of enterocyte damage; for example, small bowel ischemia or hypoxia, sepsis, systemic inflammatory response syndrome, or absence of enteral feeding. RECENT FINDINGS Two enterocyte biomarkers may help the intensivist to identify enterocyte damage and dysfunction, namely plasma citrulline, a biomarker of functional enterocyte mass, and plasma or urinary intestinal fatty acid-binding protein, a marker of enterocyte damage. This review focuses on results obtained with these biomarkers in the context of critical care, in particular: prevalence of enterocyte biomarker abnormalities; mechanisms associated with enterocyte damage and dysfunction; link with systemic inflammation, bacterial translocation, and clinical intestinal dysfunction; prognostic value of enterocyte biomarkers. Lastly, we also review the limits of these biomarkers. SUMMARY Enterocyte biomarkers may help the intensivist to identify patients presenting with intestinal damage, and who are at risk of bacterial translocation and systemic inflammatory response syndrome, as well as those with decreased enterocyte function, at risk of malabsorption. Enterocyte biomarkers should be interpreted with caution in the critically ill and should be interpreted within the overall clinical context of the patient.
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Elbaradey GF, Elshmaa NS, Hodeib H. The effect of atrial natriuretic peptide infusion on intestinal injury in septic shock. J Anaesthesiol Clin Pharmacol 2016; 32:470-475. [PMID: 28096577 PMCID: PMC5187611 DOI: 10.4103/0970-9185.194778] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND AND AIMS The aim of this study is to assess the effect of atrial natriuretic peptide (ANP) on intestinal ischemia-reperfusion injury in septic shock. MATERIAL AND METHODS A prospective randomized controlled, observer-blinded study was carried out in surgical Intensive Care Unit (ICU), University Hospital. Forty adult patients in septic shock were randomly divided into two groups, control group (Group C) received normal saline and ANP group (Group A) patients received ANP in the form of 1.5 mg vial added to 250 ml solvent in plastic bag (1 ml = 6 micg) given at 2 mcg/kg intravenous bolus over 1 min followed by 0.01 mcg/kg/min for 24 h. The primary outcome measurements were blood marker of intestinal hypoperfusion in form of intestinal fatty acid binding protein (I-FABP), malondialdehyde (MDA), myloperoxidase enzyme activity (MPO), protein carbonyl (PC), and glutathione peroxidase activity (GPA) measured before start of ANP infusion, 6 h, 12 h, and 24 h after start of infusion. The secondary outcome measurements were the duration of noradrenaline infusion, duration of ICU stay, hospital mortality rate, and complications related to ANP. RESULTS In comparison with Group C, Group A showed a significant decrease (P < 0.05) in serum level of MPO, MDA, PC, and I-FABP, with a significant increase (P < 0.05) in serum level of GPA, 6 h, 12 h, and 24 h after the start of ANP infusion. There was significant decrease (P < 0.05) in mean duration of noradrenaline infusion, the length of ICU stay and mortality rate in Group A in comparison with Group C. In Group A, seven patients had mean arterial blood pressure < 65 mmHg but respond to volume resuscitation, three patients serum sodium was 125-130 mmol/L. CONCLUSION In cases of septic shock, concomitant administration of ANP with noradrenaline may have a protective effect against intestinal injury through a decrease in the level of intestinal hypoperfusion owing to its anti-inflammatory and antioxidant effect.
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Affiliation(s)
- Ghada F. Elbaradey
- Department of Anesthesia and Surgical ICU, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Nagat Sayed Elshmaa
- Department of Anesthesia and Surgical ICU, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Hossam Hodeib
- Department of Clinical Pathology, Faculty of Medicine, Tanta University, Tanta, Egypt
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Intestinal Permeability in Inflammatory Bowel Disease: Pathogenesis, Clinical Evaluation, and Therapy of Leaky Gut. Mediators Inflamm 2015; 2015:628157. [PMID: 26582965 PMCID: PMC4637104 DOI: 10.1155/2015/628157] [Citation(s) in RCA: 481] [Impact Index Per Article: 48.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2015] [Accepted: 09/21/2015] [Indexed: 12/13/2022] Open
Abstract
The pathogenesis of inflammatory bowel disease (IBD) is multifactorial with data suggesting the role of a disturbed interaction between the gut and the intestinal microbiota. A defective mucosal barrier may result in increased intestinal permeability which promotes the exposition to luminal content and triggers an immunological response that promotes intestinal inflammation. IBD patients display several defects in the many specialized components of mucosal barrier, from the mucus layer composition to the adhesion molecules that regulate paracellular permeability. These alterations may represent a primary dysfunction in Crohn's disease, but they may also perpetuate chronic mucosal inflammation in ulcerative colitis. In clinical practice, several studies have documented that changes in intestinal permeability can predict IBD course. Functional tests, such as the sugar absorption tests or the novel imaging technique using confocal laser endomicroscopy, allow an in vivo assessment of gut barrier integrity. Antitumor necrosis factor-α (TNF-α) therapy reduces mucosal inflammation and restores intestinal permeability in IBD patients. Butyrate, zinc, and some probiotics also ameliorate mucosal barrier dysfunction but their use is still limited and further studies are needed before considering permeability manipulation as a therapeutic target in IBD.
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Early Detection of Junctional Adhesion Molecule-1 (JAM-1) in the Circulation after Experimental and Clinical Polytrauma. Mediators Inflamm 2015; 2015:463950. [PMID: 26556956 PMCID: PMC4628652 DOI: 10.1155/2015/463950] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2015] [Revised: 07/28/2015] [Accepted: 07/29/2015] [Indexed: 01/31/2023] Open
Abstract
Severe tissue trauma-induced systemic inflammation is often accompanied by evident or occult blood-organ barrier dysfunctions, frequently leading to multiple organ dysfunction. However, it is unknown whether specific barrier molecules are shed into the circulation early after trauma as potential indicators of an initial barrier dysfunction. The release of the barrier molecule junctional adhesion molecule-1 (JAM-1) was investigated in plasma of C57BL/6 mice 2 h after experimental mono- and polytrauma as well as in polytrauma patients (ISS ≥ 18) during a 10-day period. Correlation analyses were performed to indicate a linkage between JAM-1 plasma concentrations and organ failure. JAM-1 was systemically detected after experimental trauma in mice with blunt chest trauma as a driving force. Accordingly, JAM-1 was reduced in lung tissue after pulmonary contusion and JAM-1 plasma levels significantly correlated with increased protein levels in the bronchoalveolar lavage as a sign for alveolocapillary barrier dysfunction. Furthermore, JAM-1 was markedly released into the plasma of polytrauma patients as early as 4 h after the trauma insult and significantly correlated with severity of disease and organ dysfunction (APACHE II and SOFA score). The data support an early injury- and time-dependent appearance of the barrier molecule JAM-1 in the circulation indicative of a commencing trauma-induced barrier dysfunction.
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Hovens IB, van Leeuwen BL, Nyakas C, Heineman E, van der Zee EA, Schoemaker RG. Prior infection exacerbates postoperative cognitive dysfunction in aged rats. Am J Physiol Regul Integr Comp Physiol 2015; 309:R148-59. [PMID: 25972458 DOI: 10.1152/ajpregu.00002.2015] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2015] [Accepted: 05/07/2015] [Indexed: 01/07/2023]
Abstract
Older patients may experience persisting postoperative cognitive dysfunction (POCD), which is considered to largely depend on surgery-induced (neuro)inflammation. We hypothesize that inflammatory events before surgery could predispose patients to POCD. When part of our aged rats developed Mycoplasma pulmonis, this presented the unique opportunity to investigate whether a pulmonary infection before surgery influences surgery-induced neuroinflammation and POCD. Male 18-mo-old Wistar rats that had recovered from an active mycoplasma infection (infection) and control rats (healthy) were subjected to abdominal surgery and jugular vein catheterization under general anesthesia (surgery) or remained naïve (control). In postoperative week 2, behavioral tests were performed to assess cognitive performance and exploratory behavior. The acute systemic inflammatory response was investigated by measuring plasma IL-6 and IL-12. In the hippocampus, prefrontal cortex and striatum, microglial activity, neurogenesis, and concentrations of IL-6, IL-12, IL1B, and brain-derived neurotropic factor on postoperative day 14 were determined. Rats still showed signs of increased neuroinflammatory activity, as well as cognitive and behavioral changes, 3 wk after the symptoms of infection had subsided. Rats that had experienced infection before surgery exhibited a more generalized and exacerbated postoperative cognitive impairment compared with healthy surgery rats, as well as a prolonged increase in systemic cytokine levels and increased microglial activation in the hippocampus and prefrontal cortex. These findings support the hypothesis that an infection before surgery under general anesthesia exacerbates POCD. Future studies are necessary to determine whether the found effects are aging specific and to investigate the magnitude and time course of this effect in a controlled manner.
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Affiliation(s)
- Iris B Hovens
- Department of Neurobiology, GELIFES, University of Groningen, Groningen, The Netherlands; Department of Surgery and Surgical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; and
| | - Barbara L van Leeuwen
- Department of Surgery and Surgical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; and
| | - Csaba Nyakas
- Department of Neurobiology, GELIFES, University of Groningen, Groningen, The Netherlands; Behavioral Physiology Research Unite, Department of Morphology and Physiology, Health Science Faculty, Semmelweis University, Budapest, Hungary
| | - Erik Heineman
- Department of Surgery and Surgical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; and
| | - Eddy A van der Zee
- Department of Neurobiology, GELIFES, University of Groningen, Groningen, The Netherlands
| | - Regien G Schoemaker
- Department of Neurobiology, GELIFES, University of Groningen, Groningen, The Netherlands
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de Jong W, Cleveringa A, Greijdanus B, Meyer P, Heineman E, Hulscher J. The effect of acute alcohol intoxication on gut wall integrity in healthy male volunteers; a randomized controlled trial. Alcohol 2015; 49:65-70. [PMID: 25559494 DOI: 10.1016/j.alcohol.2014.09.033] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2014] [Revised: 09/13/2014] [Accepted: 09/18/2014] [Indexed: 10/24/2022]
Abstract
The aim of the study is to determine the effect of acute alcohol consumption on enterocytes. Chronic alcohol consumption has been known to induce a decrease in gut wall integrity in actively drinking alcoholics and patients with alcohol-induced liver disease. Data on the extent of the damage induced by acute alcohol consumption in healthy human beings is scarce. Studies show that heavy incidental alcohol consumption is a growing problem in modern society. Data on this matter may provide insights into the consequences of this behavior for healthy individuals. In a randomized clinical trial in crossover design, 15 healthy volunteers consumed water one day and alcohol the other. One blood sample was collected pre-consumption, five every hour post-consumption, and one after 24 h. Intestinal fatty acid binding protein (I-FABP) was used as a marker for enterocyte damage. Liver fatty acid binding protein (L-FABP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT) were used as markers for hepatocyte damage. Lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14) were used as a measure of translocation. Interleukin-6 (IL-6) was used to assess the acute inflammatory response to endotoxemia. Alcohol consumption caused a significant increase in serum I- and L-FABP levels, compared to water consumption. Levels increased directly post-consumption and decreased to normal levels within 4 h. LBP, sCD14, and IL-6 levels were not significantly higher in the alcohol group. Moderate acute alcohol consumption immediately damages the enterocyte but does not seem to cause endotoxemia.
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Strang SG, Van Waes OJF, Van der Hoven B, Ali S, Verhofstad MHJ, Pickkers P, Van Lieshout EMM. Intestinal fatty acid binding protein as a marker for intra-abdominal pressure-related complications in patients admitted to the intensive care unit; study protocol for a prospective cohort study (I-Fabulous study). Scand J Trauma Resusc Emerg Med 2015; 23:6. [PMID: 25591785 PMCID: PMC4324026 DOI: 10.1186/s13049-015-0088-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2014] [Accepted: 01/05/2015] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) have detrimental effects on all organ systems and are associated with increased morbidity and mortality in critically ill patients admitted to an intensive care unit. Intra-bladder measurement of the intra-abdominal pressure (IAP) is currently the gold standard. However, IAH is not always indicative of intestinal ischemia, which is an early and rapidly developing complication. Sensitive biomarkers for intestinal ischemia are needed to be able to intervene before damage becomes irreversible. Gut wall integrity loss, including epithelial cell disruption and tight junctions breakdown, is an early event in intestinal damage. Intestinal Fatty Acid Binding Protein (I-FABP) is excreted in urine and blood specifically from damaged intestinal epithelial cells. Claudin-3 is a specific protein which is excreted in urine following disruption of intercellular tight junctions. This study aims to investigate if I-FABP and Claudin-3 can be used as a diagnostic tool for identifying patients at risk for IAP-related complications. METHODS/DESIGN In a multicenter, prospective cohort study 200 adult patients admitted to the intensive care unit with at least two risk factors for IAH as defined by the World Society of the Abdominal Compartment Syndrome (WSACS) will be included. Patients in whom an intra-bladder IAP measurement is contra-indicated or impossible and patients with inflammatory bowel diseases that may affect I-FABP levels will be excluded. The IAP will be measured using an intra-bladder technique. During the subsequent 72 hours, the IAP measurement will be repeated every six hours. At these time points, a urine and serum sample will be collected for measurement of I-FABP and Claudin-3 levels. Clinical outcome of patients during their stay at the intensive care unit will be monitored using the Sequential Organ Failure Assessment (SOFA) score. DISCUSSION Successful completion of this trial will provide evidence on the eventual role of the biomarkers I-FABP and Claudin-3 in predicting the risk of IAP-associated adverse outcome. This may aid early (surgical) intervention. TRIAL REGISTRATION The trial is registered at the Netherlands Trial Register (NTR4638).
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Adam N, Sorensen V, Skinner R. Not all intestinal traumatic injuries are the same: a comparison of surgically treated blunt vs. penetrating injuries. Injury 2015; 46:115-8. [PMID: 25088986 DOI: 10.1016/j.injury.2014.07.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2014] [Revised: 07/02/2014] [Accepted: 07/11/2014] [Indexed: 02/02/2023]
Abstract
PURPOSE Traumatic intestinal injuries are less common with blunt compared to penetrating mechanisms of trauma and blunt injuries are often associated with diagnostic delays. The purpose of this study is to evaluate differences in the characteristics and outcomes between blunt and penetrating intestinal injuries to facilitate insight into optimal recognition and management. METHODS A retrospective analysis of trauma admissions from January 2009 to June 2011 was performed. Patient demographics, ISS, early shock, injury type, timing to OR, blood loss and transfusions, surgical management, infections, EC fistulas, enteric leaks, LOS and mortality were compared. RESULTS Demographics - There was 3866 blunt admissions and 966 penetrating admissions to our level II trauma centre (Total n=4832) during this interval. The final study group comprised n=131 patients treated for intestinal injuries. Blunt n=54 (BI) vs. penetrating (PI) n=77. Age was similar between the groups: (BI 34 SD 12 vs. PI 30 SD 12). Comorbid conditions were similar as were ED hypotension and blood transfusions. Blunt mechanisms had higher ISS; BI (20 SD 14) vs. PI (16 SD 12), p=0.08 and organ specific injury scales were higher in blunt injuries. Operative Management - Time to operation was higher in BI: (500 SD 676min vs. PI 110 SD 153min, p=0.01). The use of an open abdomen technique was higher for BI: n=19 (35%) vs. PI: n=5 (6%), p=<0.001, as well as delayed intestinal repair in damage control cases. Outcomes - Anastomotic leaks were more prevalent in BI: n=4 (7%) vs. PI: n=2 (3%), p=0.38. Enteric fistulas were: (BI n=8 (15%), vs. PI n=2 (3%), p=0.02). Surgical site infections and other nosocomial infections were: (BI n=11 (20%) vs. PI n=4 (5%), p=0.02), (BI n=11 (20%) vs. PI n=2 (3%), p=0.002), respectively. Hospital and ICU LOS was: (BI=20 SD 14 vs. PI=11 SD 11, p=0.001), (BI=10 SD 10 vs. PI=5 SD 5, p=0.01) respectively. These differences were reflected in higher hospital charges in BI. CONCLUSIONS Blunt and penetrating intestinal injury patterns have high injury severity. Significant operative delays occurred in the blunt injury group as well as, anastomotic failures, enteric fistulas, nosocomial infections, and higher cost. These features underscore the complexity of blunt injury patterns and warrant vigilant injury recognition to improve outcomes.
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Affiliation(s)
- Nadir Adam
- Department of Surgery, Kern Medical Center, Bakersfield, CA, United States
| | - Victor Sorensen
- Department of Surgery, Kern Medical Center, Bakersfield, CA, United States
| | - Ruby Skinner
- Department of Surgery, Kern Medical Center, Bakersfield, CA, United States.
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Intestinal permeability--a new target for disease prevention and therapy. BMC Gastroenterol 2014; 14:189. [PMID: 25407511 PMCID: PMC4253991 DOI: 10.1186/s12876-014-0189-7] [Citation(s) in RCA: 1208] [Impact Index Per Article: 109.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Accepted: 10/17/2014] [Indexed: 02/06/2023] Open
Abstract
Data are accumulating that emphasize the important role of the intestinal barrier and intestinal permeability for health and disease. However, these terms are poorly defined, their assessment is a matter of debate, and their clinical significance is not clearly established. In the present review, current knowledge on mucosal barrier and its role in disease prevention and therapy is summarized. First, the relevant terms 'intestinal barrier' and 'intestinal permeability' are defined. Secondly, the key element of the intestinal barrier affecting permeability are described. This barrier represents a huge mucosal surface, where billions of bacteria face the largest immune system of our body. On the one hand, an intact intestinal barrier protects the human organism against invasion of microorganisms and toxins, on the other hand, this barrier must be open to absorb essential fluids and nutrients. Such opposing goals are achieved by a complex anatomical and functional structure the intestinal barrier consists of, the functional status of which is described by 'intestinal permeability'. Third, the regulation of intestinal permeability by diet and bacteria is depicted. In particular, potential barrier disruptors such as hypoperfusion of the gut, infections and toxins, but also selected over-dosed nutrients, drugs, and other lifestyle factors have to be considered. In the fourth part, the means to assess intestinal permeability are presented and critically discussed. The means vary enormously and probably assess different functional components of the barrier. The barrier assessments are further hindered by the natural variability of this functional entity depending on species and genes as well as on diet and other environmental factors. In the final part, we discuss selected diseases associated with increased intestinal permeability such as critically illness, inflammatory bowel diseases, celiac disease, food allergy, irritable bowel syndrome, and--more recently recognized--obesity and metabolic diseases. All these diseases are characterized by inflammation that might be triggered by the translocation of luminal components into the host. In summary, intestinal permeability, which is a feature of intestinal barrier function, is increasingly recognized as being of relevance for health and disease, and therefore, this topic warrants more attention.
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Babu D, Motterlini R, Lefebvre RA. CO and CO-releasing molecules (CO-RMs) in acute gastrointestinal inflammation. Br J Pharmacol 2014; 172:1557-73. [PMID: 24641722 DOI: 10.1111/bph.12632] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2013] [Revised: 01/30/2014] [Accepted: 02/05/2014] [Indexed: 12/13/2022] Open
Abstract
Carbon monoxide (CO) is enzymatically generated in mammalian cells alongside the liberation of iron and the production of biliverdin and bilirubin. This occurs during the degradation of haem by haem oxygenase (HO) enzymes, a class of ubiquitous proteins consisting of constitutive and inducible isoforms. The constitutive HO2 is present in the gastrointestinal tract in neurons and interstitial cells of Cajal and CO released from these cells might contribute to intestinal inhibitory neurotransmission and/or to the control of intestinal smooth muscle cell membrane potential. On the other hand, increased expression of the inducible HO1 is now recognized as a beneficial response to oxidative stress and inflammation. Among the products of haem metabolism, CO appears to contribute primarily to the antioxidant and anti-inflammatory effects of the HO1 pathway explaining the studies conducted to exploit CO as a possible therapeutic agent. This article reviews the effects and, as far as known today, the mechanism(s) of action of CO administered either as CO gas or via CO-releasing molecules in acute gastrointestinal inflammation. We provide here a comprehensive overview on the effect of CO in experimental in vivo models of post-operative ileus, intestinal injury during sepsis and necrotizing enterocolitis. In addition, we will analyse the in vitro data obtained so far on the effect of CO on intestinal epithelial cell lines exposed to cytokines, considering the important role of the intestinal mucosa in the pathology of gastrointestinal inflammation.
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Affiliation(s)
- D Babu
- Heymans Institute of Pharmacology, Ghent University, Gent, Belgium
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Enterocyte damage in critically ill patients is associated with shock condition and 28-day mortality. Crit Care Med 2013; 41:2169-76. [PMID: 23782971 DOI: 10.1097/ccm.0b013e31828c26b5] [Citation(s) in RCA: 90] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Small bowel dysfunction in critically ill patients is frequent, underdiagnosed, and associated with poor prognosis. Intestinal fatty acid-binding protein is a marker of enterocyte damage, and plasma citrulline concentration is a marker of functional enterocyte mass. Primary objective was to identify factors associated with intestinal fatty acid-binding protein in critically ill patients. Secondary objectives were to study factors associated with plasma citrulline concentration and its correlation with intestinal fatty acid-binding protein. DESIGN Prospective observational study. SETTING ICU in a University Hospital PATIENTS Critically ill patients 18 years old or older with an expected length of ICU stay 48 hours or more, without pregnancy, chronic small bowel disease, or chronic renal failure. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Plasma intestinal fatty acid-binding protein and citrulline concentrations, and variables relating to prognosis and treatment, were measured at admission to the ICU. One hundred and three patients were included. Intestinal fatty acid-binding protein elevation at admission to the ICU was associated with catecholamine support, higher lactate concentration, higher Sequential Organ Failure Assessment score, and higher international normalized ratio (all p≤0.001). Plasma citrulline concentration less than or equal to 10 μmol/L at admission to the ICU was associated with higher intra-abdominal pressure, higher plasma C reactive protein concentration, and more frequent antibiotic use (all p≤0.005). There was no correlation between plasma levels of intestinal fatty acid-binding protein and citrulline. At ICU admission, Sequential Organ Failure Assessment score≥12, plasma citrulline≤12.2 μmol/L, and plasma intestinal fatty acid-binding protein concentration≥355 pg/mL were all independently associated with 28-day mortality (odds ratio, 4.39 [1.48-13.03]; odds ratio, 5.17 [1.59-16.86]; and odds ratio, 4.46 [1.35-14.74], respectively). CONCLUSIONS In critically ill patients, enterocyte damage is frequent, and it is significantly associated with shock and 28-day mortality. The link between intestinal fatty acid-binding protein and plasma citrulline concentrations in critically ill patients needs to be further evaluated.
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Continuous administration of enteral lipid- and protein-rich nutrition limits inflammation in a human endotoxemia model. Crit Care Med 2013; 41:1258-65. [PMID: 23388517 DOI: 10.1097/ccm.0b013e31827c0a17] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE An overzealous inflammatory response is an important cause of morbidity and mortality in surgical, trauma, and critically ill patients. Enteral administration of lipid-rich nutrition was previously shown to attenuate inflammation and reduce organ damage via a cholecystokinin-1 receptor-mediated vagovagal reflex in animal studies. The current preclinical study investigates the immunomodulatory potential of a custom-made enteral nutrition during systemic inflammation in man. DESIGN Double-blind, randomized controlled trial. SETTING Intensive care research unit. SUBJECTS Male volunteers. INTERVENTIONS After an overnight fast, 18 healthy male subjects received an IV bolus of Escherichia coli lipopolysaccharide (2 ng/kg). Subjects in the fasted group (n = 6) were deprived of food throughout the study, while subjects in the intervention groups were fed either custom-made lipid- and protein-rich nutrition (n = 6) or isocaloric control nutrition (n = 6) via nasojejunal tube, starting 1 hour prior to lipopolysaccharide administration until 6 hours afterward. MEASUREMENTS AND MAIN RESULTS Bolus lipopolysaccharide administration resulted in a marked inflammatory response. Continuous postpyloric administration of nutrition significantly increased plasma cholecystokinin levels throughout the lipopolysaccharide-induced inflammatory response. Lipid- and protein-rich nutrition attenuated circulating levels of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6 and the interleukin-1 receptor antagonist compared with control nutrition (all p < 0.05) and fasted subjects (all p < 0.05). In additional, lipid- and protein-rich nutrition augmented the anti-inflammatory response, reflected by increased plasma levels of interleukin-10 compared with fasted subjects (p < 0.0001). CONCLUSIONS The current preclinical study expands the immunomodulating effects of enteral nutrition as previously observed in rodents to man. Continuous administration of enteral nutrition resulted in a rapid anti-inflammatory effect. Furthermore, enrichment of the nutritional composition with lipid and protein was shown to enhance the anti-inflammatory potential. Therefore, continuous enteral administration of lipid- and protein-rich nutrition is a promising intervention to modulate the immune response in the early course of systemic inflammation in man.
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Wu BG, Peng TC, Tsai PS, Wang TY, Jeng MJ, Huang CJ. High-lipid enteral nutrition could partially mitigate inflammation but not lung injury in hemorrhagic shock rats. J Surg Res 2013; 184:997-1005. [PMID: 23622726 DOI: 10.1016/j.jss.2013.03.085] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2012] [Revised: 03/05/2013] [Accepted: 03/27/2013] [Indexed: 01/13/2023]
Abstract
BACKGROUND Loss of gut barrier function is crucial in mediating lung injury induced by hemorrhagic shock/resuscitation (HS). High-lipid enteral nutrition (HL) can preserve gut barrier function. We hypothesized that HL could also mitigate HS-induced lung injury. MATERIALS AND METHODS Forty-eight adult male rats were randomly assigned to one of four experimental groups: HS; HS-HL; Sham; Sham-HL. HS was induced by blood drawing and mean blood pressure was maintained at 40-45 mmHg for 120 min followed by resuscitation with re-infusion of exsanguinated blood/saline mixtures. HL gavage was performed at 45 min before blood drawing and at the end of resuscitation. RESULTS Intestinal permeability of the HS group was significantly higher than that of the Sham group (P < 0.001). Pulmonary concentrations of malondialdehyde (lipid peroxidation) and inflammatory molecules, including prostaglandin E2, tumor necrosis factor-α, interleukin-6, and macrophage inflammatory protein-2, of the HS group were significantly higher than those of the Sham group. Histologic analyses, including histopathology, wet/dry weight ratio, and neutrophil infiltration revealed moderate lung injury in the HS group. In contrast, intestinal permeability (P < 0.001) and pulmonary concentrations of tumor necrosis factor-α and macrophage inflammatory protein-2 (P = 0.021 and 0.01) of the HS-HL group were significantly lower than those of the HS group. However, pulmonary concentrations of malondialdehyde, prostaglandin E2, and interleukin-6 of the HS-HL and HS groups were comparable. Moreover, histologic analyses also revealed moderate lung injury in the HS-HL group. CONCLUSIONS High-lipid enteral nutrition significantly mitigated gut barrier loss and partially mitigated lung inflammation but not oxidation and lung injury in hemorrhagic shock/resuscitation rats.
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Affiliation(s)
- Bor-Gang Wu
- Department of Surgery, Buddhist Tzu Chi General Hospital, Taipei Branch, Taipei, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan; Institute of Emergency and Critical Care Medicine, National Yang-Ming University, Taipei, Taiwan
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van Wijck K, Pennings B, van Bijnen AA, Senden JMG, Buurman WA, Dejong CHC, van Loon LJC, Lenaerts K. Dietary protein digestion and absorption are impaired during acute postexercise recovery in young men. Am J Physiol Regul Integr Comp Physiol 2013; 304:R356-61. [DOI: 10.1152/ajpregu.00294.2012] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Previously, we demonstrated that exercise can cause small intestinal injury, leading to loss of gut barrier function. The functional consequences of such exercise-induced intestinal injury on subsequent food digestion and absorption are unclear. The present study determined the impact of resistance-type exercise on small intestinal integrity and in vivo dietary protein digestion and absorption kinetics. Twenty-four young males ingested 20 g specifically produced intrinsically l-[1-13C]phenylalanine-labeled protein at rest or after performing a single bout of resistance-type exercise. Continuous intravenous infusions with l-[ring-2H5]phenylalanine were employed, and blood samples were collected regularly to assess in vivo protein digestion and absorption kinetics and to quantify plasma levels of intestinal fatty-acid binding protein (I-FABP) as a measure of small intestinal injury. Plasma I-FABP levels were increased after exercise by 35%, reaching peak values of 344 ± 53 pg/ml compared with baseline 254 ± 31 pg/ml ( P < 0.05). In resting conditions, I-FABP levels remained unchanged. Dietary protein digestion and absorption rates were reduced during postexercise recovery when compared with resting conditions ( P < 0.001), with average peak exogenous phenylalanine appearance rates of 0.18 ± 0.04 vs. 0.23 ± 0.03 mmol phenylalanine·kg lean body mass−1·min−1, respectively. Plasma I-FABP levels correlated with in vivo rates of dietary protein digestion and absorption ( r S = −0.57, P < 0.01). Resistance-type exercise induces small intestinal injury in healthy, young men, causing impairments in dietary protein digestion and absorption kinetics during the acute postexercise recovery phase. To the best of our knowledge, this is first evidence that shows that exercise attenuates dietary protein digestion and absorption kinetics during acute postexercise recovery.
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Affiliation(s)
- Kim van Wijck
- Top Institute Food and Nutrition, Wageningen, the Netherlands
- Department of Surgery, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands; and
| | - Bart Pennings
- Top Institute Food and Nutrition, Wageningen, the Netherlands
- Department of Human Movement Sciences, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Annemarie A. van Bijnen
- Department of Human Movement Sciences, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Joan M. G. Senden
- Department of Human Movement Sciences, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Wim A. Buurman
- Top Institute Food and Nutrition, Wageningen, the Netherlands
- Department of Surgery, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands; and
| | - Cornelis H. C. Dejong
- Top Institute Food and Nutrition, Wageningen, the Netherlands
- Department of Surgery, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands; and
| | - Luc J. C. van Loon
- Top Institute Food and Nutrition, Wageningen, the Netherlands
- Department of Human Movement Sciences, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Kaatje Lenaerts
- Top Institute Food and Nutrition, Wageningen, the Netherlands
- Department of Surgery, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands; and
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Andrade BB, Hullsiek KH, Boulware DR, Rupert A, French MA, Ruxrungtham K, Montes ML, Price H, Barreiro P, Audsley J, Sher A, Lewin SR, Sereti I. Biomarkers of inflammation and coagulation are associated with mortality and hepatitis flares in persons coinfected with HIV and hepatitis viruses. J Infect Dis 2013; 207:1379-88. [PMID: 23335804 DOI: 10.1093/infdis/jit033] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) and/or hepatitis B virus (HBV) coinfection with human immunodeficiency virus (HIV) has a greater risk of mortality than either HCV or HBV infection alone and is frequently associated with hepatitis flares after antiretroviral therapy (ART) initiation. METHODS We performed a retrospective cohort study of 287 HIV-positive persons coinfected with HBV and/or HCV (70 had HBV coinfection only, 207 had HCV coninfection only, and 10 had HBV and HCV coinfections) who had pre-ART plasma samples evaluated for biomarkers associated with death (within 4 years) and/or hepatitis flare (within 4 months) after ART initiation. A predictive biomarker risk score was calculated. RESULTS Forty-eight deaths and 50 hepatitis flares occurred. Nonsurvivors were older, had more prior AIDS-defining events, and had higher pre-ART triglycerides and aspartate transaminase levels. Detectable hyaluronic acid and higher d-dimer, interleukin 6, interleukin 8, and soluble CD14 levels were associated with death in univariate models and with a composite biomarker risk score. The risk of hepatitis flares was higher with HBV coinfection only (24.3%) and with HBV and HCV coinfection (50%) than with HCV coinfection only (13.5%). Higher levels of alanine transaminase and interleukin 10 were also associated with hepatitis flares. CONCLUSIONS Among HIV-positive patients coinfected with HBV and/or HCV who are initiating ART, biomarkers of inflammation and coagulation are associated with an increased risk of death, whereas HBV coinfection and higher pre-ART interleukin 10 levels are associated with hepatitis flares.
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Zahs A, Bird MD, Ramirez L, Turner JR, Choudhry MA, Kovacs EJ. 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. [PMID: 22790598 PMCID: PMC3468533 DOI: 10.1152/ajpgi.00157.2012] [Citation(s) in RCA: 79] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Laboratory evidence suggests that intestinal permeability is elevated following either binge ethanol exposure or burn injury alone, and this barrier dysfunction is further perturbed when these insults are combined. We and others have previously reported a rise in both systemic and local proinflammatory cytokine production in mice after the combined insult. Knowing that long myosin light-chain kinase (MLCK) is important for epithelial barrier maintenance and can be activated by proinflammatory cytokines, we examined whether inhibition of MLCK alleviated detrimental intestinal responses seen after ethanol exposure and burn injury. To accomplish this, mice were given vehicle or a single binge ethanol exposure followed by a sham or dorsal scald burn injury. Following injury, one group of mice received membrane permeant inhibitor of MLCK (PIK). At 6 and 24 h postinjury, bacterial translocation and intestinal levels of proinflammatory cytokines were measured, and changes in tight junction protein localization and total intestinal morphology were analyzed. Elevated morphological damage, ileal IL-1β and IL-6 levels, and bacterial translocation were seen in mice exposed to ethanol and burn injury relative to either insult alone. This increase was not seen in mice receiving PIK after injury. Ethanol-exposed and burn-injured mice had reduced zonula occludens protein-1 and occludin localization to the tight junction relative to sham-injured mice. However, the observed changes in junctional complexes were not seen in our PIK-treated mice following the combined insult. These data suggest that MLCK activity may promote morphological and inflammatory responses in the ileum following ethanol exposure and burn injury.
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Affiliation(s)
- Anita Zahs
- 2 Molecular and Cellular Biochemistry Program, ,3Burn and Shock Trauma Institute, and ,4Alcohol Research Program, Loyola University, Medical Center, Maywood, Illinois; and
| | - Melanie D. Bird
- 1Department of Surgery, ,3Burn and Shock Trauma Institute, and ,4Alcohol Research Program, Loyola University, Medical Center, Maywood, Illinois; and
| | - Luis Ramirez
- 1Department of Surgery, ,3Burn and Shock Trauma Institute, and
| | - Jerrold R. Turner
- 5Department of Pathology, The University of Chicago, Chicago, Illinois
| | - Mashkoor A. Choudhry
- 1Department of Surgery, ,3Burn and Shock Trauma Institute, and ,4Alcohol Research Program, Loyola University, Medical Center, Maywood, Illinois; and
| | - Elizabeth J. Kovacs
- 1Department of Surgery, ,2 Molecular and Cellular Biochemistry Program, ,3Burn and Shock Trauma Institute, and ,4Alcohol Research Program, Loyola University, Medical Center, Maywood, Illinois; and
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Grimaldi D, Guivarch E, Neveux N, Fichet J, Pène F, Marx JS, Chiche JD, Cynober L, Mira JP, Cariou A. Markers of intestinal injury are associated with endotoxemia in successfully resuscitated patients. Resuscitation 2012; 84:60-5. [PMID: 22743354 DOI: 10.1016/j.resuscitation.2012.06.010] [Citation(s) in RCA: 90] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2011] [Revised: 05/29/2012] [Accepted: 06/05/2012] [Indexed: 01/15/2023]
Abstract
AIMS Gut dysfunction is suspected to play a major role in the pathophysiology of post-resuscitation disease through an increase in intestinal permeability and endotoxin release. However this dysfunction often remains occult and is poorly investigated. The aim of this pilot study was to explore intestinal failure biomarkers in post-cardiac arrest patients and to correlate them with endotoxemia. METHODS Following resuscitation after cardiac arrest, 21 patients were prospectively studied. Urinary intestinal fatty acid-binding protein (IFABP), which marks intestinal permeability, plasma citrulline, which reflects the functional enterocyte mass, and whole blood endotoxin were measured at admission, days 1-3 and 6. We explored the kinetics of release and the relationship between IFABP, citrulline and endotoxin values. RESULTS IFABP was extremely high at admission and normalized at D3 (6668 pg/mL vs 39 pg/mL, p=0.01). Lowest median of citrulline (N=20-40 μmol/L) was attained at D2 (11 μmol/L at D2 vs 24 μmol/L at admission, p=0.01) and tended to normalize at D6 (21 μmol/L). During ICU stay, 86% of patients presented a detectable endotoxemia. Highest endotoxin level was positively correlated with highest IFABP level (R(2)=0.31, p=0.01) and was inversely correlated with lowest plasma citrulline levels (R(2)=0.55, p<0.001). Endotoxin levels increased between admission and D2 in patients with post-resuscitation shock, whereas it decreases in patients with no shock (median +0.33 EU vs -0.19 EU, p=0.03). Highest endotoxin level was positively correlated with D3 SOFA score (R(2)=0.45, p=0.004). CONCLUSION Biomarkers of intestinal injury are altered after cardiac arrest and are associated with endotoxemia. This could worsen post-resuscitation shock and organ failure.
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Affiliation(s)
- D Grimaldi
- Medical Intensive Care Unit, Groupe Hospitalier Broca Cochin Hotel-Dieu, AP-HP, 27 rue du Faubourg Saint Jacques, 75679 Paris Cedex 14, France
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Snoek SA, Dhawan S, van Bree SH, Cailotto C, van Diest SA, Duarte JM, Stanisor OI, Hilbers FW, Nijhuis L, Koeman A, van den Wijngaard RM, Zuurbier CJ, Boeckxstaens GE, de Jonge WJ. Mast cells trigger epithelial barrier dysfunction, bacterial translocation and postoperative ileus in a mouse model. Neurogastroenterol Motil 2012; 24:172-84, e91. [PMID: 22122661 DOI: 10.1111/j.1365-2982.2011.01820.x] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Abdominal surgery involving bowel manipulation commonly results in inflammation of the bowel wall, which leads to impaired intestinal motility and postoperative ileus (POI). Mast cells have shown to play a key role in the pathogenesis of POI in mouse models and human studies. We studied whether mast cells contribute to the pathogenesis of POI by eliciting intestinal barrier dysfunction. METHODS C57BL/6 mice, and two mast cell-deficient mutant mice Kit(W/W-v) , and Kit(W-sh/W-sh) underwent laparotomy (L) or manipulation of the small bowel (IM). Postoperative inflammatory infiltrates and cytokine production were assessed. Epithelial barrier function was determined in Ussing chambers, by measuring transport of luminal particles to the vena mesenterica, and by assessing bacterial translocation. KEY RESULTS In WT mice, IM resulted in pro-inflammatory cytokine and chemokine production, and neutrophil extravasation to the manipulated bowel wall. This response to IM was reduced in mast cell-deficient mice. IM caused epithelial barrier dysfunction in WT mice, but not in the two mast cell-deficient strains. IM resulted in a decrease in mean arterial pressure in both WT and mast cell-deficient mice, indicating that impaired barrier function was not explained by tissue hypoperfusion, but involved mast cell mediators. CONCLUSIONS & INFERENCES Mast cell activation during abdominal surgery causes epithelial barrier dysfunction and inflammation of the muscularis externa of the bowel. The impairment of the epithelial barrier likely contributes to the pathogenesis of POI. Our data further underscore that mast cells are bona fide cellular targets to ameliorate POI.
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Affiliation(s)
- S A Snoek
- Tytgat Institute for Liver and Intestinal Research, Academic Medical Centre, Amsterdam, The Netherlands
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