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Oami T, Yamamoto A, Ishida S, Kondo K, Hata N, Oshima T. Critical Care Nutrition from a Metabolic Point of View: A Narrative Review. Nutrients 2025; 17:1352. [PMID: 40284216 PMCID: PMC12029973 DOI: 10.3390/nu17081352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2025] [Revised: 04/08/2025] [Accepted: 04/14/2025] [Indexed: 04/29/2025] Open
Abstract
Background: Critical illness induces profound metabolic alterations, characterized by a hypermetabolic state, insulin resistance, protein catabolism, and gut barrier dysfunction, which contribute to increased morbidity and mortality. Emerging evidence highlights the role of the gut microbiome and its metabolites in modulating systemic inflammation and immune responses during critical illness. This narrative review explores the metabolic evolution of critically ill patients, the impact of gut dysbiosis on disease progression, and the potential role of nutrition in modulating metabolism and improving patient outcomes. Methods: A comprehensive literature search was conducted across PubMed and Google Scholar for articles published up to February 2025. Search terms included "critical illness", "metabolism", "gut microbiota", "nutrition", and related keywords. Articles published in English addressing metabolic alterations, microbiome changes, and nutritional strategies in critically ill patients were included. After screening for eligibility, relevant articles were synthesized to outline current knowledge and identify gaps. Results: Metabolic changes in critical illness progress through distinct phases, from catabolism-driven hypermetabolism to gradual recovery. Gut dysbiosis, characterized by a loss of microbial diversity and increased gut permeability, contributes to systemic inflammation and organ dysfunction. Nutritional strategies, including enteral nutrition, probiotics, prebiotics, and metabolomics-driven interventions, may help restore microbial balance, preserve gut barrier integrity, and modulate immune and metabolic responses. Future nutrition therapy should focus on metabolic modulation rather than solely addressing nutrient deficits. Conclusions: Advances in gut microbiome research and metabolomics offer new avenues for personalized nutrition strategies tailored to the metabolic demands of critically ill patients. Integrating these approaches may improve clinical and functional recovery while mitigating the long-term consequences of critical illness.
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Affiliation(s)
- Takehiko Oami
- Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, Chiba 260-8677, Japan; (T.O.)
| | - Akiyuki Yamamoto
- Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, Chiba 260-8677, Japan; (T.O.)
| | - Shigenobu Ishida
- Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, Chiba 260-8677, Japan; (T.O.)
| | - Kengo Kondo
- Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, Chiba 260-8677, Japan; (T.O.)
| | - Nanami Hata
- Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, Chiba 260-8677, Japan; (T.O.)
| | - Taku Oshima
- Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, Chiba 260-8677, Japan; (T.O.)
- Institute for Advanced Academic Research, Chiba University, Chiba 263-8522, Japan
- Research Institute of Disaster Medicine, Chiba University, Chiba 263-8522, Japan
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Oami T, Shimazui T, Yumoto T, Otani S, Hayashi Y, Coopersmith CM. Gut integrity in intensive care: alterations in host permeability and the microbiome as potential therapeutic targets. J Intensive Care 2025; 13:16. [PMID: 40098052 PMCID: PMC11916345 DOI: 10.1186/s40560-025-00786-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2025] [Accepted: 02/21/2025] [Indexed: 03/19/2025] Open
Abstract
BACKGROUND The gut has long been hypothesized to be the "motor" of critical illness, propagating inflammation and playing a key role in multiple organ dysfunction. However, the exact mechanisms through which impaired gut integrity potentially contribute to worsened clinical outcome remain to be elucidated. Critical elements of gut dysregulation including intestinal hyperpermeability and a perturbed microbiome are now recognized as potential therapeutic targets in critical care. MAIN BODY The gut is a finely tuned ecosystem comprising ~ 40 trillion microorganisms, a single cell layer intestinal epithelia that separates the host from the microbiome and its products, and the mucosal immune system that actively communicates in a bidirectional manner. Under basal conditions, these elements cooperate to maintain a finely balanced homeostasis benefitting both the host and its internal microbial community. Tight junctions between adjacent epithelial cells selectively transport essential molecules while preventing translocation of pathogens. However, critical illness disrupts gut barrier function leading to increased gut permeability, epithelial apoptosis, and immune activation. This disruption is further exacerbated by a shift in the microbiome toward a "pathobiome" dominated by pathogenic microbes with increased expression of virulence factors, which intensifies systemic inflammation and accelerates organ dysfunction. Research has highlighted several potential therapeutic targets to restore gut integrity in the host, including the regulation of epithelial cell function, modulation of tight junction proteins, and inhibition of epithelial apoptosis. Additionally, microbiome-targeted therapies, such as prebiotics, probiotics, fecal microbiota transplantation, and selective decontamination of the digestive tract have also been extensively investigated to promote restoration of gut homeostasis in critically ill patients. Future research is needed to validate the potential efficacy of these interventions in clinical settings and to determine if the gut can be targeted in an individualized fashion. CONCLUSION Increased gut permeability and a disrupted microbiome are common in critical illness, potentially driving dysregulated systemic inflammation and organ dysfunction. Therapeutic strategies to modulate gut permeability and restore the composition of microbiome hold promise as novel treatments for critically ill patients.
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Affiliation(s)
- Takehiko Oami
- Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, 101 Woodruff Circle, Suite WMB 5105, Atlanta, GA, 30322, USA
- Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Takashi Shimazui
- Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, 101 Woodruff Circle, Suite WMB 5105, Atlanta, GA, 30322, USA
- Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Tetsuya Yumoto
- Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, 101 Woodruff Circle, Suite WMB 5105, Atlanta, GA, 30322, USA
- Department of Emergency, Critical Care and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Shunsuke Otani
- Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, 101 Woodruff Circle, Suite WMB 5105, Atlanta, GA, 30322, USA
- Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Yosuke Hayashi
- Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, 101 Woodruff Circle, Suite WMB 5105, Atlanta, GA, 30322, USA
- Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Craig M Coopersmith
- Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, 101 Woodruff Circle, Suite WMB 5105, Atlanta, GA, 30322, USA.
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Derman ID, Moses JC, Rivera T, Ozbolat IT. Understanding the cellular dynamics, engineering perspectives and translation prospects in bioprinting epithelial tissues. Bioact Mater 2025; 43:195-224. [PMID: 39386221 PMCID: PMC11462153 DOI: 10.1016/j.bioactmat.2024.09.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 09/04/2024] [Accepted: 09/18/2024] [Indexed: 10/12/2024] Open
Abstract
The epithelium is one of the important tissues in the body as it plays a crucial barrier role serving as a gateway into and out of the body. Most organs in the body contain an epithelial tissue component, where the tightly connected, organ-specific epithelial cells organize into cysts, invaginations, or tubules, thereby performing distinct to endocrine or exocrine secretory functions. Despite the significance of epithelium, engineering functional epithelium in vitro has remained a challenge due to it is special architecture, heterotypic composition of epithelial tissues, and most importantly, difficulty in attaining the apico-basal and planar polarity of epithelial cells. Bioprinting has brought a paradigm shift in fabricating such apico-basal polarized tissues. In this review, we provide an overview of epithelial tissues and provide insights on recapitulating their cellular arrangement and polarization to achieve epithelial function. We describe the different bioprinting techniques that have been successful in engineering polarized epithelium, which can serve as in vitro models for understanding homeostasis and studying diseased conditions. We also discuss the different attempts that have been investigated to study these 3D bioprinted engineered epithelium for preclinical use. Finally, we highlight the challenges and the opportunities that need to be addressed for translation of 3D bioprinted epithelial tissues towards paving way for personalized healthcare in the future.
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Affiliation(s)
- Irem Deniz Derman
- Engineering Science and Mechanics Department, Penn State University, University Park, PA, 16802, USA
- The Huck Institutes of the Life Sciences, Penn State University, University Park, PA, 16802, USA
| | - Joseph Christakiran Moses
- Engineering Science and Mechanics Department, Penn State University, University Park, PA, 16802, USA
- The Huck Institutes of the Life Sciences, Penn State University, University Park, PA, 16802, USA
| | - Taino Rivera
- Biomedical Engineering Department, Penn State University, University Park, PA, 16802, USA
| | - Ibrahim T. Ozbolat
- Engineering Science and Mechanics Department, Penn State University, University Park, PA, 16802, USA
- The Huck Institutes of the Life Sciences, Penn State University, University Park, PA, 16802, USA
- Biomedical Engineering Department, Penn State University, University Park, PA, 16802, USA
- Materials Research Institute, Penn State University, University Park, PA, 16802, USA
- Cancer Institute, Penn State University, University Park, PA, 16802, USA
- Neurosurgery Department, Penn State University, University Park, PA, 16802, USA
- Department of Medical Oncology, Cukurova University, Adana, 01330, Turkey
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Sinder SB, Sharma SV, Shirvaikar IS, Pradhyumnan H, Patel SH, Cabeda Diaz I, Perez GG, Bramlett HM, Raval AP. Impact of menopause-associated frailty on traumatic brain injury. Neurochem Int 2024; 176:105741. [PMID: 38621511 DOI: 10.1016/j.neuint.2024.105741] [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] [Received: 02/03/2024] [Revised: 04/01/2024] [Accepted: 04/09/2024] [Indexed: 04/17/2024]
Abstract
Navigating menopause involves traversing a complex terrain of hormonal changes that extend far beyond reproductive consequences. Menopausal transition is characterized by a decrease in estradiol-17β (E2), and the impact of menopause resonates not only in the reproductive system but also through the central nervous system, musculoskeletal, and gastrointestinal domains. As women undergo menopausal transition, they become more susceptible to frailty, amplifying the risk and severity of injuries, including traumatic brain injury (TBI). Menopause triggers a cascade of changes leading to a decline in muscle mass, accompanied by diminished tone and excitability, thereby restricting the availability of irisin, a crucial hormone derived from muscles. Concurrently, bone mass undergoes reduction, culminating in the onset of osteoporosis and altering the dynamics of osteocalcin, a hormone originating from bones. The diminishing levels of E2 during menopause extend their influence on the gut microbiota, resulting in a reduction in the availability of tyrosine, tryptophan, and serotonin metabolites, affecting neurotransmitter synthesis and function. Understanding the interplay between menopause, frailty, E2 decline, and the intricate metabolisms of bone, gut, and muscle is imperative when unraveling the nuances of TBI after menopause. The current review underscores the significance of accounting for menopause-associated frailty in the incidence and consequences of TBI. The review also explores potential mechanisms to enhance gut, bone, and muscle health in menopausal women, aiming to mitigate frailty and improve TBI outcomes.
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Affiliation(s)
- Sophie B Sinder
- Peritz Scheinberg Cerebral Vascular Disease Research Laboratory (CVDRL), Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Sabrina V Sharma
- Peritz Scheinberg Cerebral Vascular Disease Research Laboratory (CVDRL), Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Isha S Shirvaikar
- Peritz Scheinberg Cerebral Vascular Disease Research Laboratory (CVDRL), Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Hari Pradhyumnan
- Peritz Scheinberg Cerebral Vascular Disease Research Laboratory (CVDRL), Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Shahil H Patel
- Peritz Scheinberg Cerebral Vascular Disease Research Laboratory (CVDRL), Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Indy Cabeda Diaz
- Peritz Scheinberg Cerebral Vascular Disease Research Laboratory (CVDRL), Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Gina G Perez
- Peritz Scheinberg Cerebral Vascular Disease Research Laboratory (CVDRL), Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Helen M Bramlett
- Department of Neurological Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA; The Miami Project to Cure Paralysis, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA; Bruce W. Carter Department of Veterans Affairs Medical Center, Miami, FL, USA
| | - Ami P Raval
- Peritz Scheinberg Cerebral Vascular Disease Research Laboratory (CVDRL), Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA; Bruce W. Carter Department of Veterans Affairs Medical Center, Miami, FL, USA
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Quispe-Medina K, Pacheco-Aranibar J, Mamani-Ruelas A, Gamez-Bernabé C, Zapana-Begazo R, Paz-Aliaga I, Villanueva Salas J, Bernabé-Ortiz JC. Characterization of Pulmonary Bacteriobiota in Critically Ill Patients in Southern Peru through Next-Generation Sequencing Technology. Curr Issues Mol Biol 2023; 45:10041-10055. [PMID: 38132473 PMCID: PMC10742510 DOI: 10.3390/cimb45120627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 11/24/2023] [Indexed: 12/23/2023] Open
Abstract
Sequence variation in the 16S gene is widely used to characterize diverse microbial communities. This was the first pilot study carried out in our region where the pulmonary microbiota of critically ill patients was investigated and analyzed, with the aim of finding a specific profile for these patients that can be used as a diagnostic marker. An study of critical patients mechanically ventilated for non-respiratory indications, in a polyvalent intensive care unit, was carried out; samplee were extracted by endotracheal aspiration and subsequently the microbiota was characterized through Next-Generation Sequencing Technology (NGS). The predominant phyla among the critically ill patients were Proteobacteria, Firmicutes and Bacteroidata. In the surviving patients group, the predominant phyla were Proteobacteria, Bacteroidata and Firmicutes, in the group of deceased patients thy were Firmicutes, Proteobacteria, and Bacteroidata. We found a decrease in commensal bacteria in deceased patients and a progressive increase in in-hospital germs.
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Affiliation(s)
- Katherine Quispe-Medina
- Post-Graduate School, Universidad Católica de Santa María, Urb. San José s/n, Umacollo, Arequipa 04013, Peru; (K.Q.-M.); (R.Z.-B.); (J.V.S.)
| | - Jani Pacheco-Aranibar
- Department of Molecular Biology, Instituto de Biotecnología del ADN Uchumayo, Arequipa 04400, Peru;
| | - Angel Mamani-Ruelas
- Emergency and Critical Care Department, Hospital Nacional Carlos Alberto Seguín Escobedo—EsSalud, Calle Peral s/n, Arequipa 04001, Peru;
| | - Carlos Gamez-Bernabé
- Human Medicine School, Faculty of Health Sciences, Universidad Nacional Jorge Basadre Grohmann, Av. Miraflores s/n, Tacna 23001, Peru;
| | - Rosemary Zapana-Begazo
- Post-Graduate School, Universidad Católica de Santa María, Urb. San José s/n, Umacollo, Arequipa 04013, Peru; (K.Q.-M.); (R.Z.-B.); (J.V.S.)
| | - Ivan Paz-Aliaga
- Department of Pharmacy, Biochemistry and Biotechnology, Universidad Católica de Santa María, Urb. San José s/n, Umacollo, Arequipa 04013, Peru;
| | - Jose Villanueva Salas
- Post-Graduate School, Universidad Católica de Santa María, Urb. San José s/n, Umacollo, Arequipa 04013, Peru; (K.Q.-M.); (R.Z.-B.); (J.V.S.)
| | - Julio C. Bernabé-Ortiz
- Post-Graduate School, Universidad Católica de Santa María, Urb. San José s/n, Umacollo, Arequipa 04013, Peru; (K.Q.-M.); (R.Z.-B.); (J.V.S.)
- Department of Molecular Biology, Instituto de Biotecnología del ADN Uchumayo, Arequipa 04400, Peru;
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Tian Y, Dhara S, Barrett CD, Richman AP, Brahmbhatt TS. Antibiotic use in acute mesenteric ischemia: a review of the evidence and call to action. Thromb J 2023; 21:39. [PMID: 37041639 PMCID: PMC10088293 DOI: 10.1186/s12959-023-00486-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Accepted: 04/03/2023] [Indexed: 04/13/2023] Open
Abstract
Acute mesenteric ischemia (AMI) is a life-threatening condition with a high mortality rate. The standard practice after making the diagnosis includes aggressive resuscitation, anticoagulation, followed by revascularization and resection of necrotic bowel. The role of empiric antibiotics in the management of AMI is not well defined in the literature. This review article aims to examine our current understanding on this matter, based on bench research and clinical studies. It is demonstrated in animal study model that the ischemia/reperfusion (I/R) injury damages intestinal epithelium, and subsequently lead to barrier dysfunction, a condition that can support bacterial translocation through a complex interplay between the intestinal epithelium, the intestinal immune system and the intestine's endogenous bacterial population. Based on this mechanism, it is possible that the use of antibiotics may help mitigate the consequences of I/R injury, which is examined in few animal studies. In clinical practice, many guidelines support the use of prophylactic antibiotics, based on a meta-analysis of randomized control trials (RCTs) demonstrating the benefit of antibiotics in multi-organ dysfunction syndrome. However, there is no direct reference to AMI in this meta-analysis. Most clinical studies that focus on AMI and mentions the use of antibiotics are retrospective and single institution, and very few comments on the role of antibiotics in their discussions. We conclude that there is limited evidence in literature to support the use of prophylactic antibiotic in AMI to improve outcome. More clinical studies with high level of evidence and basic science research are needed to improve our understanding on this topic and ultimately help build a better clinical pathway for patients with AMI.
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Affiliation(s)
- Yuqian Tian
- Division of Acute Care Surgery and Surgical Critical Care, Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA
| | - Sanjeev Dhara
- Division of Vascular Surgery, Department of Surgery, Emory University, Atlanta, GA, USA
| | - Christopher D Barrett
- Division of Acute Care Surgery and Surgical Critical Care, Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA
| | - Aaron P Richman
- Divisions of Trauma and Acute Care Surgery and Surgical Critical Care, Department of Surgery, Boston University Medical Center, Boston University School of Medicine, Boston, MA, USA
| | - Tejal S Brahmbhatt
- Divisions of Trauma and Acute Care Surgery and Surgical Critical Care, Department of Surgery, Boston University Medical Center, Boston University School of Medicine, Boston, MA, USA.
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Abstract
PURPOSE OF REVIEW Study of organ crosstalk in critical illness has uncovered complex biological communication between different organ systems, but the role of microbiota in organ crosstalk has received limited attention. We highlight the emerging understanding of the gut-lung axis, and how the largest biomass of the human body in the gut may affect lung physiology in critical illness. RECENT FINDINGS Disruption of healthy gut microbial communities and replacement by disease-promoting pathogens (pathobiome) generates a maladaptive transmitter of messages from the gut to the lungs, connected via the portal venous and the mesenteric lymphatic systems. Gut barrier impairment allows for microbial translocation (living organisms or cellular fragments) to the lungs. Host-microbiota interactions in the gut mucosa can also impact lung physiology through microbial metabolite secretion or host-derived messengers (hormones, cytokines or immune cells). Clinical examples like the prevention of ventilator-associated pneumonia by selective decontamination of the digestive tract show that the gut-lung axis can be manipulated therapeutically. SUMMARY A growing body of evidence supports the pathophysiological relevance of the gut-lung axis, yet we are only at the brink of understanding the therapeutic and prognostic relevance of the gut microbiome, metabolites and host-microbe interactions in critical illness.
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Affiliation(s)
- Sridesh Nath
- Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine
| | - Georgios D Kitsios
- Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine
- Acute Lung Injury Center of Excellence
- Center for Medicine and the Microbiome, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Lieuwe D J Bos
- Intensive Care
- Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Amsterdam University Medical Centers, location AMC, University of Amsterdam, Amsterdam, The Netherlands
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Huang R, Lu Y, Jin M, Liu Y, Zhang M, Xian S, Chang Z, Wang L, Zhang W, Lu J, Tong X, Wang S, Zhu Y, Huang J, Jiang L, Gu M, Huang Z, Wu M, Ji S. A bibliometric analysis of the role of microbiota in trauma. Front Microbiol 2023; 14:1091060. [PMID: 36819034 PMCID: PMC9932281 DOI: 10.3389/fmicb.2023.1091060] [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: 11/06/2022] [Accepted: 01/09/2023] [Indexed: 02/05/2023] Open
Abstract
Introduction Over the last several decades, the gut microbiota has been implicated in the formation and stabilization of health, as well as the development of disease. With basic and clinical experiments, scholars are gradually understanding the important role of gut microbiota in trauma, which may offer novel ideas of treatment for trauma patients. In this study, we purposed to summarize the current state and access future trends in gut microbiota and trauma research. Methods We retrieved relevant documents and their published information from the Web of Science Core Collection (WoSCC). Bibliometrix package was responsible for the visualized analysis. Results Totally, 625 documents were collected and the number of annual publications kept increasing, especially from 2016. China published the most documents while the USA had the highest local citations. The University of Colorado and Food & Function are respectively the top productive institution and journal, as PLOS One is the most local cited journal. With the maximum number of articles and local citations, Deitch EA is supported to be the most contributive author. Combining visualized analysis of keywords and documents and literature reading, we recognized two key topics: bacteria translocation in trauma and gut microbiota's effect on inflammation in injury, especially in nervous system injury. Discussion The impact of gut microbiota on molecular and pathological mechanism of inflammation is the focus now. In addition, the experiments of novel therapies based on gut microbiota's impact on trauma are being carried out. We hope that this study can offer a birds-eye view of this field and promote the gradual improvement of it.
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Affiliation(s)
- Runzhi Huang
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, China,Research Unit of Key Techniques for Treatment of Burns and Combined Burns and Trauma Injury, Chinese Academy of Medical Sciences, Beijing, China
| | - Yuwei Lu
- Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Minghao Jin
- Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yifan Liu
- Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Mengyi Zhang
- Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shuyuan Xian
- Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhengyan Chang
- Department of Pathology, Shanghai Tenth People's Hospital, Tongji University of Medicine, Shanghai, China
| | - Lei Wang
- Beijing Genomics Institute (BGI), Shenzhen, China
| | - Wei Zhang
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, China,Research Unit of Key Techniques for Treatment of Burns and Combined Burns and Trauma Injury, Chinese Academy of Medical Sciences, Beijing, China
| | - Jianyu Lu
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, China,Research Unit of Key Techniques for Treatment of Burns and Combined Burns and Trauma Injury, Chinese Academy of Medical Sciences, Beijing, China
| | - Xirui Tong
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, China,Research Unit of Key Techniques for Treatment of Burns and Combined Burns and Trauma Injury, Chinese Academy of Medical Sciences, Beijing, China
| | - Siqiao Wang
- Tongji University School of Medicine, Shanghai, China
| | - Yushu Zhu
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, China,Research Unit of Key Techniques for Treatment of Burns and Combined Burns and Trauma Injury, Chinese Academy of Medical Sciences, Beijing, China
| | - Jie Huang
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, China,Research Unit of Key Techniques for Treatment of Burns and Combined Burns and Trauma Injury, Chinese Academy of Medical Sciences, Beijing, China
| | - Luofeng Jiang
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, China,Research Unit of Key Techniques for Treatment of Burns and Combined Burns and Trauma Injury, Chinese Academy of Medical Sciences, Beijing, China
| | - Minyi Gu
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, China,Research Unit of Key Techniques for Treatment of Burns and Combined Burns and Trauma Injury, Chinese Academy of Medical Sciences, Beijing, China
| | - Zongqiang Huang
- Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China,*Correspondence: Zongqiang Huang ✉
| | - Minjuan Wu
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, China,Research Unit of Key Techniques for Treatment of Burns and Combined Burns and Trauma Injury, Chinese Academy of Medical Sciences, Beijing, China,Minjuan Wu ✉
| | - Shizhao Ji
- Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, China,Research Unit of Key Techniques for Treatment of Burns and Combined Burns and Trauma Injury, Chinese Academy of Medical Sciences, Beijing, China,Shizhao Ji ✉
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Pape HC, Moore EE, McKinley T, Sauaia A. Pathophysiology in patients with polytrauma. Injury 2022; 53:2400-2412. [PMID: 35577600 DOI: 10.1016/j.injury.2022.04.009] [Citation(s) in RCA: 57] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 04/13/2022] [Indexed: 02/02/2023]
Abstract
The pathophysiology after polytrauma represents a complex network of interactions. While it was thought for a long time that the direct and indirect effects of hypoperfusion are most relevant due to the endothelial permeability changes, it was discovered that the innate immune response to trauma is equally important in modifying the organ response. Recent multi center studies provided a "genetic storm" theory, according to which certain neutrophil changes are activated at the time of injury. However, a second hit phenomenon can be induced by activation of certain molecules by direct organ injury, or pathogens (damage associated molecular patterns, DAMPS - pathogen associated molecular patterns, PAMPS). The interactions between the four pathogenetic cycles (of shock, coagulopathy, temperature loss and soft tissue injuries) and cross-talk between coagulation and inflammation have also been identified as important modifiers of the clinical status. In a similar fashion, overzealous surgeries and their associated soft tissue injury and blood loss can induce secondary worsening of the patient condition. Therefore, staged surgeries in certain indications represent an important alternative, to allow for performing a "safe definitive surgery" strategy for major fractures. The current review summarizes all these situations in a detailed fashion.
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Affiliation(s)
- H-C Pape
- Department of Trauma, University Hospital Zurich, University of Zurich, Raemistrasse 100, 8091 Zurich, Switzerland.
| | - E E Moore
- Department of Surgery, Ernest E Moore Shock Trauma Center at Denver Health, University of Colorado, Aurora, CO, USA.
| | - T McKinley
- Department of Orthopaedics, Indiana University, 200 Hawkins Dr, Iowa City, IA 52242, USA.
| | - A Sauaia
- Schools of Public Health and Medicine, University of Colorado, Aurora, Colorado, USA.
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Emodin Ameliorates Intestinal Dysfunction by Maintaining Intestinal Barrier Integrity and Modulating the Microbiota in Septic Mice. Mediators Inflamm 2022; 2022:5026103. [PMID: 35677734 PMCID: PMC9168211 DOI: 10.1155/2022/5026103] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 03/26/2022] [Accepted: 04/21/2022] [Indexed: 12/12/2022] Open
Abstract
Sepsis-induced inflammatory response leads to intestinal damage and secondary bacterial translocation, causing systemic infections and eventually death. Emodin is a natural anthraquinone derivative in many plants with promising bioactivities. However, the effects and mechanisms of emodin on sepsis-induced intestinal dysfunctions have not been well clarified yet. We found that emodin treatment suppressed the inflammatory response in the intestines of septic mice. Intestinal barrier function was also improved by emodin through enhancing ZO-1 and occludin expression, which prevented the secondary translocation of Escherichia coli. By proteome microarray investigation, JNK2 was identified as a direct target of emodin. In vitro study also showed that emodin inhibited LPS-induced inflammatory response in intestinal epithelial cells. Nuclear factors including NF-κB and AP-1 were further identified as downstream effectors of JNK2. Bioinformatic analysis based on 16s rRNA gene sequencing illustrated that emodin treatment significantly increased the alpha- and beta-diversity of gut microbiota in septic mice. Moreover, data according to functional prediction showed that emodin decreased the abundance of potential pathogenic bacteria in gut. Our findings have shown that emodin treatment prevented inflammatory induced barrier dysfunction and decreased the potential pathogenicity of lumen bacteria, reducing the hazard of lumen bacterial translocation during sepsis.
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Zhan L, Pu J, Zheng J, Hang S, Pang L, Dai M, Ji C. Tetrastigma hemsleyanum Diels et Gilg ameliorates lipopolysaccharide induced sepsis via repairing the intestinal mucosal barrier. Biomed Pharmacother 2022; 148:112741. [PMID: 35217279 DOI: 10.1016/j.biopha.2022.112741] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 02/15/2022] [Accepted: 02/17/2022] [Indexed: 11/02/2022] Open
Abstract
OBJECTIVE Sepsis causes excessive systemic inflammation and leads to multiple organ dysfunction syndrome (MODS). The intestine plays a key role in the occurrence and development of sepsis. Tetrastigma hemsleyanum Diels et Gilg (San ye qing, SYQ), a precious Chinese medicine, has been widely used for centuries due to its high traditional value, such as a remarkable anti-inflammatory effect. However, the role of SYQ in intestinal permeability during the development of sepsis needs to be discovered. METHODS Mice were intraperitoneally injected with lipopolysaccharide (LPS) to simulate intestinal mucosal barrier function damage in sepsis. Pathological section, inflammatory cytokines, tight junctions, cell apoptosis, and intestinal flora were detected to evaluate the protective effect of SYQ on intestinal mucosal barrier injury in LPS-induced septic mice. RESULTS The results showed that SYQ treatment obviously attenuated LPS-induced intestinal injury and reduced the production of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6). Besides, SYQ also up-regulated the expressions of tight junctions, including Zonula occludens 1 (ZO-1), Claudin-5, and Occludin along with a decreased in the levels of myosin light chain kinase (MLCK) and myosin light chain (MLC). In addition, SYQ down-regulated the expression of Bax/Bcl2 as well as that of cleaved caspase-3 to prevent the cells from undergoing apoptosis. Further, SYQ restored the diversity of the intestinal flora, increased the abundance of Firmicutes, and decreased the abundance of Bacteroidota. CONCLUSIONS The study indicated that SYQ exerted its protective effect on intestinal mucosal barrier injury in LPS-induced septic mice by reducing inflammatory response, improving the tight junction protein expression, inhibiting cell apoptosis, and adjusting the intestinal flora structure.
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Affiliation(s)
- Lianghui Zhan
- Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310014, China; Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, Zhejiang 310014, China
| | - Jinbao Pu
- Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310014, China; Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, Zhejiang 310014, China
| | - Jingru Zheng
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310014, China
| | - Suni Hang
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310014, China
| | - Lisha Pang
- Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310014, China
| | - Muhua Dai
- Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310014, China
| | - Chunlian Ji
- Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310014, China.
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12
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Rahman S, Ghiboub M, Donkers JM, van de Steeg E, van Tol EAF, Hakvoort TBM, de Jonge WJ. The Progress of Intestinal Epithelial Models from Cell Lines to Gut-On-Chip. Int J Mol Sci 2021; 22:ijms222413472. [PMID: 34948271 PMCID: PMC8709104 DOI: 10.3390/ijms222413472] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 12/07/2021] [Accepted: 12/13/2021] [Indexed: 12/12/2022] Open
Abstract
Over the past years, several preclinical in vitro and ex vivo models have been developed that helped to understand some of the critical aspects of intestinal functions in health and disease such as inflammatory bowel disease (IBD). However, the translation to the human in vivo situation remains problematic. The main reason for this is that these approaches fail to fully reflect the multifactorial and complex in vivo environment (e.g., including microbiota, nutrition, and immune response) in the gut system. Although conventional models such as cell lines, Ussing chamber, and the everted sac are still used, increasingly more sophisticated intestinal models have been developed over the past years including organoids, InTESTine™ and microfluidic gut-on-chip. In this review, we gathered the most recent insights on the setup, advantages, limitations, and future perspectives of most frequently used in vitro and ex vivo models to study intestinal physiology and functions in health and disease.
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Affiliation(s)
- Shafaque Rahman
- Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, 1105 BK Amsterdam, The Netherlands; (S.R.); (M.G.); (T.B.M.H.)
| | - Mohammed Ghiboub
- Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, 1105 BK Amsterdam, The Netherlands; (S.R.); (M.G.); (T.B.M.H.)
- Department of Pediatric Gastroenterology and Nutrition, Amsterdam University Medical Centers, Emma Children’s Hospital, 1105 AZ Amsterdam, The Netherlands
| | - Joanne M. Donkers
- The Netherlands Organization for Applied Scientific Research (TNO), 3704 HE Zeist, The Netherlands; (J.M.D.); (E.v.d.S.); (E.A.F.v.T.)
| | - Evita van de Steeg
- The Netherlands Organization for Applied Scientific Research (TNO), 3704 HE Zeist, The Netherlands; (J.M.D.); (E.v.d.S.); (E.A.F.v.T.)
| | - Eric A. F. van Tol
- The Netherlands Organization for Applied Scientific Research (TNO), 3704 HE Zeist, The Netherlands; (J.M.D.); (E.v.d.S.); (E.A.F.v.T.)
| | - Theodorus B. M. Hakvoort
- Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, 1105 BK Amsterdam, The Netherlands; (S.R.); (M.G.); (T.B.M.H.)
| | - Wouter J. de Jonge
- Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, 1105 BK Amsterdam, The Netherlands; (S.R.); (M.G.); (T.B.M.H.)
- Department of Surgery, University of Bonn, 53113 Bonn, Germany
- Correspondence:
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McClave SA. Can feeding strategies alter immune signaling and gut sepsis in critical illness? JPEN J Parenter Enteral Nutr 2021; 45:66-73. [PMID: 34477220 DOI: 10.1002/jpen.2260] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 08/19/2021] [Accepted: 08/31/2021] [Indexed: 11/06/2022]
Abstract
The insult necessitating admission to the intensive care unit propels the patient along a course involving increasing oxidative stress, immune dysregulation, and adverse outcomes. As the largest immune organ with the greatest microbial burden, the gastrointestinal tract may change the speed and direction the patient follows along this pathway. The gut's influence is mediated by a complex process of cross-talk immune signaling between the intestinal epithelium, the liver, and the microbiome. Agents which invoke this response vary from mitochondrial DNA, inflammatory cytokines, and bacterial organisms to short chain fatty acids and bile salts. The site of action of these agents again varies widely from Pattern Recognition Receptors, G protein receptors, and Farnesoid X receptors in the gut and liver to transcriptional factors in epithelial cells, hepatocytes, macrophages, and neutrophils. While the initial focus of response may be local within the gastrointestinal tract and liver, the process extends in a systemic manner to affect immune tissue and various organs at distant sites. The gut can modulate this cross-talk signaling through numerous strategies in design of nutritional therapy. The physiologic response to luminal nutrients and short chain fatty acids, and more novel approaches like use phosphorylated polyethylene glycol, bovine serum-derived immunoglobulin, and specialized pro-resolving molecules may help slow disease progression and even reverse the patient's course toward one of health and recovery. The optimal benefit to be derived from nutritional therapy may have more to do with the degree to which immune cross-talk signaling can be modified by such innovative strategies. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Stephen A McClave
- Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Louisville School of Medicine
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14
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Mauser M, Kruger D, Pather S, Plani F. Trauma results in immune cell-induced intestinal epithelial damage with subsequently increased sepsis rate. J Trauma Acute Care Surg 2021; 90:565-573. [PMID: 33264268 DOI: 10.1097/ta.0000000000003043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND The detrimental effect of trauma on the immune system has been a subject of interest for decades. The gut-associated lymphoid tissue (GALT) of the bowel that encompasses different lymphocyte subpopulations may be an important pillar of human immunity in the context of trauma. Neither the short-term histological trauma-induced changes in the GALT nor its impact on the outcome after trauma surgery has been investigated. METHODS This prospective, longitudinal proof-of-concept study included patients who required damage-control surgery after abdominal gunshot wounds with small bowel involvement. Bowel specimens were obtained during the index and relook operations, and the T-lymphocytic quantity therein was analyzed via immunohistochemistry. We scrutinized how the lymphocyte structure and numbers of the GALT altered, and whether the extent and nature of these changes had an impact on the postoperative outcome with regard to septic and surgical complications. RESULTS A total of 31 damage-control patients were recruited for the study. The main histological changes between the index and relook specimen was a shift of CD8+ T cells from the lamina propria (LP) into the epithelium and a decrease of T lymphocytes in the LP. The significant increase of the intraepithelial CD8+ T cells was associated with a more extensive enterocyte apoptosis, and correlated significantly, positively with the number of postoperative septic complications. CONCLUSION Our data support that trauma induces an immune cell-driven impairment of the intestinal epithelium, as well as an increased apoptosis of lymphocytes in the LP, which is associated with a worse clinical outcome. The underlying mechanism suggests that a therapeutic approach to minimize apoptosis in the intestine may impact the outcome of severely injured trauma patients. LEVEL OF EVIDENCE Therapeutic/care/management, level lV.
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Affiliation(s)
- Martin Mauser
- From the Department of Surgery, Faculty of Health Sciences (M.M., D.K.), Chris Hani Baragwanath Academic Hospital, University of the Witwatersrand Medical School, Parktown, Johannesburg; National Health Laboratory Service, School of Pathology (S.P.), Chris Hani Baragwanath Academic Hospital, Faculty of Health Sciences, University of the Witwatersrand, Gauteng (S.P.); and Faculty of Health Sciences (F.P.), Chris Hani Baragwanath Academic Hospital, University of the Witwatersrand Medical School, Parktown, Johannesburg, South Africa
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15
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Ma Y, Yang X, Chatterjee V, Wu MH, Yuan SY. The Gut-Lung Axis in Systemic Inflammation. Role of Mesenteric Lymph as a Conduit. Am J Respir Cell Mol Biol 2021; 64:19-28. [PMID: 32877613 DOI: 10.1165/rcmb.2020-0196tr] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Emerging evidence shows that after injury or infection, the mesenteric lymph acts as a conduit for gut-derived toxic factors to enter the blood circulation, causing systemic inflammation and acute lung injury. Neither the cellular and molecular identity of lymph factors nor their mechanisms of action have been well understood and thus have become a timely topic of investigation. This review will first provide a summary of background knowledge on gut barrier and mesenteric lymphatics, followed by a discussion focusing on the current understanding of potential injurious factors in the lymph and their mechanistic contributions to lung injury. We also examine lymph factors with antiinflammatory properties as well as the bidirectional nature of the gut-lung axis in inflammation.
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Affiliation(s)
- Yonggang Ma
- Department of Molecular Pharmacology and Physiology, and
| | - Xiaoyuan Yang
- Department of Molecular Pharmacology and Physiology, and
| | | | - Mack H Wu
- Department of Surgery, University of South Florida Morsani College of Medicine, Tampa, Florida
| | - Sarah Y Yuan
- Department of Molecular Pharmacology and Physiology, and.,Department of Surgery, University of South Florida Morsani College of Medicine, Tampa, Florida
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16
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de Jager P, Smith O, Pool R, Bolon S, Richards GA. Review of the pathophysiology and prognostic biomarkers of immune dysregulation after severe injury. J Trauma Acute Care Surg 2021; 90:e21-e30. [PMID: 33075024 DOI: 10.1097/ta.0000000000002996] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Affiliation(s)
- Pieter de Jager
- From the Department of Anaesthesiology (P.d.J., O.S., S.B.), School of Clinical Medicine, University of the Witwatersrand, Johannesburg; Department of Haematology (R.P.), National Health Laboratory Service, University of Pretoria, Pretoria; and Division of Critical Care (G.A.R.), School of Clinical Medicine, University of the Witwatersrand, Johannesburg, South Africa
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17
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Longhitano Y, Zanza C, Thangathurai D, Taurone S, Kozel D, Racca F, Audo A, Ravera E, Migneco A, Piccioni A, Franceschi F. Gut Alterations in Septic Patients: A Biochemical Literature Review. Rev Recent Clin Trials 2021; 15:289-297. [PMID: 32781963 DOI: 10.2174/1574887115666200811105251] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2020] [Revised: 06/04/2020] [Accepted: 06/19/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Sepsis is a life-threatening organ dysfunction with high mortality and morbidity rate and with the disease progression many alterations are observed in different organs. The gastrointestinal tract is often damaged during sepsis and septic shock and main symptoms are related to increased permeability, bacterial translocation and malabsorption. These intestinal alterations can be both cause and effect of sepsis. OBJECTIVE The aim of this review is to analyze different pathways that lead to intestinal alteration in sepsis and to explore the most common methods for intestinal permeability measurement and, at the same time to evaluate if their use permit to identify patients at high risk of sepsis and eventually to estimate the prognosis. MATERIAL AND METHODS The peer-reviewed articles analyzed were selected from PubMed databases using the keywords "sepsis" "gut alteration", "bowel permeability", "gut alteration", "bacterial translocation", "gut permeability tests", "gut inflammation". Among the 321 papers identified, 190 articles were selected, after title - abstract examination and removing the duplicates and studies on pediatric population,only 105 articles relating to sepsis and gut alterations were analyzed. RESULTS Integrity of the intestinal barrier plays a key role in the preventing of bacterial translocation and gut alteration related to sepsis. It is obvious that this dysfunction of the small intestine can have serious consequences and the early identification of patients at risk - to develop malabsorption or already malnourished - is very recommended to increase the survivor rate. Until now, in critical patients, the dosage of citrullinemia is easily applied test in clinical setting, in fact, it is relatively easy to administer and allows to accurately assess the functionality of enterocytes. CONCLUSION The sepsis can have an important impact on the gastrointestinal function. In addition, the alteration of the permeability can become a source of systemic infection. At the moment, biological damage markers are not specific, but the dosage of LPS, citrulline, lactulose/mannitol test, FABP and fecal calprotectin are becoming an excellent alternative with high specificity and sensitivity.
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Affiliation(s)
- Yaroslava Longhitano
- Department of Anesthesia and Critical Care Medicine, St. Antonio and Biagio and Cesare Arrigo Hospital, Alessandria, Italy
| | - Christian Zanza
- Department of Anesthesia and Critical Care Medicine, St. Antonio and Biagio and Cesare Arrigo Hospital, Alessandria, Italy
| | - Duraiyah Thangathurai
- Department of Anesthesiology, Keck Medical School of University of Southern California, Los Angeles, United States
| | - Samanta Taurone
- Department of Sensory Organs, Sapienza University of Rome, Rome, Italy
| | - Daniela Kozel
- Department of Anesthesia and Critical Care Medicine, St. Antonio and Biagio and Cesare Arrigo Hospital, Alessandria, Italy
| | - Fabrizio Racca
- Department of Anesthesia and Critical Care Medicine, St. Antonio and Biagio and Cesare Arrigo Hospital, Alessandria, Italy
| | - Andrea Audo
- Department of Anesthesia and Critical Care Medicine, St. Antonio and Biagio and Cesare Arrigo Hospital, Alessandria, Italy
| | - Enrico Ravera
- Department of Emergency, Anesthesia and Critical Care, Michele and Pietro Ferrero Hospital, Verduno, Italy
| | - Alessio Migneco
- Department of Anesthesiology and Emergency Sciences,, Policlinico Gemelli/IRCCS - Catholic University of Sacred Heart, Rome, Italy
| | - Andrea Piccioni
- Department of Anesthesiology and Emergency Sciences,, Policlinico Gemelli/IRCCS - Catholic University of Sacred Heart, Rome, Italy
| | - Francesco Franceschi
- Department of Anesthesiology and Emergency Sciences,, Policlinico Gemelli/IRCCS - Catholic University of Sacred Heart, Rome, Italy
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18
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Clements TW, Tolonen M, Ball CG, Kirkpatrick AW. Secondary Peritonitis and Intra-Abdominal Sepsis: An Increasingly Global Disease in Search of Better Systemic Therapies. Scand J Surg 2021; 110:139-149. [PMID: 33406974 DOI: 10.1177/1457496920984078] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Secondary peritonitis and intra-abdominal sepsis are a global health problem. The life-threatening systemic insult that results from intra-abdominal sepsis has been extensively studied and remains somewhat poorly understood. While local surgical therapy for perforation of the abdominal viscera is an age-old therapy, systemic therapies to control the subsequent systemic inflammatory response are scarce. Advancements in critical care have led to improved outcomes in secondary peritonitis. The understanding of the effect of secondary peritonitis on the human microbiome is an evolving field and has yielded potential therapeutic targets. This review of secondary peritonitis discusses the history, classification, pathophysiology, diagnosis, treatment, and future directions of the management of secondary peritonitis. Ongoing clinical studies in the treatment of secondary peritonitis and the open abdomen are discussed.
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Affiliation(s)
- T W Clements
- Foothills Medical Centre, Department of Critical Care Medicine and Surgery, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - M Tolonen
- HUS Helsinki University Hospital, Helsinki, Finland
| | - C G Ball
- Foothills Medical Centre, Department of Critical Care Medicine and Surgery, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - A W Kirkpatrick
- Foothills Medical Centre, Department of Critical Care Medicine and Surgery, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.,Canadian Forces Medical Services, University of Calgary, Calgary, AB, Canada
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19
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Kirkpatrick AW, Hamilton DR, McKee JL, MacDonald B, Pelosi P, Ball CG, Roberts D, McBeth PB, Cocolini F, Ansaloni L, Peireira B, Sugrue M, Campbell MR, Kimball EJ, Malbrain MLNG, Roberts D. Do we have the guts to go? The abdominal compartment, intra-abdominal hypertension, the human microbiome and exploration class space missions. Can J Surg 2020. [PMID: 33278908 DOI: 10.1503/cjs.019219] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Abstract
Humans are destined to explore space, yet critical illness and injury may be catastrophically limiting for extraterrestrial travel. Humans are superorganisms living in symbiosis with their microbiomes, whose genetic diversity dwarfs that of humans. Symbiosis is critical and imbalances are associated with disease, occurring within hours of serious illness and injury. There are many characteristics of space flight that negatively influence the microbiome, especially deep space itself, with its increased radiation and absence of gravity. Prolonged weightlessness causes many physiologic changes that are detrimental; some resemble aging and will adversely affect the ability to tolerate critical illness or injury and subsequent treatment. Critical illness-induced intra-abdominal hypertension (IAH) may induce malperfusion of both the viscera and microbiome, with potentially catastrophic effects. Evidence from animal models confirms profound IAH effects on the gut, namely ischemia and disruption of barrier function, mechanistically linking IAH to resultant organ dysfunction. Therefore, a pathologic dysbiome, space-induced immune dysfunction and a diminished cardiorespiratory reserve with exacerbated susceptibility to IAH, imply that a space-deconditioned astronaut will be vulnerable to IAH-induced gut malperfusion. This sets the stage for severe gut ischemia and massive biomediator generation in an astronaut with reduced cardiorespiratory/immunological capacity. Fortunately, experiments in weightless analogue environments suggest that IAH may be ameliorated by conformational abdominal wall changes and a resetting of thoracoabdominal mechanics. Thus, review of the interactions of physiologic changes with prolonged weightlessness and IAH is required to identify appropriate questions for planning exploration class space surgical care.
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Affiliation(s)
- Andrew W Kirkpatrick
- From the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Departments of Medicine and Engineering, University of Calgary, Calgary, Alta. (Kirkpatrick, Hamilton, McKee); the Departments of Critical Care Medicine and Medicine, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alta. (MacDonald); the Department of Surgical Sciences and Integrated Diagnostics, University of Genoa; Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy (Pelosi); Regional Trauma Services; Departments of Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (Ball); the Division of Vascular and Endovascular Surgery, Department of Surgery, University of Ottawa, Ottawa, Ont. (Roberts); the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Regional Trauma Services; Foothills Medical Centre; Departments of Engineering, Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (McBeth); the Departments of Trauma and Emergency Surgery, Pisa University Hospital, Pisa, Italy (Cocolini); the Departments of General, Emergency and Trauma Surgery, Bufalini Hospital, Cesena, Italy (Ansaloni); the Division of Trauma Surgery, University of Campinas, Campinas, São Paulo, Brazil (Peireira); the Department of Surgery, Letterkenny University Hospital, Letterkenny, Donegal, Ireland (Sugrue); the Paris Regional Medical Centre, Paris, Texas, United States (Campbell); the Departments of Surgery and Critical Care, Network Development and Telehealth, University of Utah, Salt Lake City, US (Kimball); the Faculties of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium (Malbrain)
| | - Douglas R Hamilton
- From the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Departments of Medicine and Engineering, University of Calgary, Calgary, Alta. (Kirkpatrick, Hamilton, McKee); the Departments of Critical Care Medicine and Medicine, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alta. (MacDonald); the Department of Surgical Sciences and Integrated Diagnostics, University of Genoa; Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy (Pelosi); Regional Trauma Services; Departments of Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (Ball); the Division of Vascular and Endovascular Surgery, Department of Surgery, University of Ottawa, Ottawa, Ont. (Roberts); the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Regional Trauma Services; Foothills Medical Centre; Departments of Engineering, Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (McBeth); the Departments of Trauma and Emergency Surgery, Pisa University Hospital, Pisa, Italy (Cocolini); the Departments of General, Emergency and Trauma Surgery, Bufalini Hospital, Cesena, Italy (Ansaloni); the Division of Trauma Surgery, University of Campinas, Campinas, São Paulo, Brazil (Peireira); the Department of Surgery, Letterkenny University Hospital, Letterkenny, Donegal, Ireland (Sugrue); the Paris Regional Medical Centre, Paris, Texas, United States (Campbell); the Departments of Surgery and Critical Care, Network Development and Telehealth, University of Utah, Salt Lake City, US (Kimball); the Faculties of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium (Malbrain)
| | - Jessica L McKee
- From the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Departments of Medicine and Engineering, University of Calgary, Calgary, Alta. (Kirkpatrick, Hamilton, McKee); the Departments of Critical Care Medicine and Medicine, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alta. (MacDonald); the Department of Surgical Sciences and Integrated Diagnostics, University of Genoa; Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy (Pelosi); Regional Trauma Services; Departments of Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (Ball); the Division of Vascular and Endovascular Surgery, Department of Surgery, University of Ottawa, Ottawa, Ont. (Roberts); the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Regional Trauma Services; Foothills Medical Centre; Departments of Engineering, Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (McBeth); the Departments of Trauma and Emergency Surgery, Pisa University Hospital, Pisa, Italy (Cocolini); the Departments of General, Emergency and Trauma Surgery, Bufalini Hospital, Cesena, Italy (Ansaloni); the Division of Trauma Surgery, University of Campinas, Campinas, São Paulo, Brazil (Peireira); the Department of Surgery, Letterkenny University Hospital, Letterkenny, Donegal, Ireland (Sugrue); the Paris Regional Medical Centre, Paris, Texas, United States (Campbell); the Departments of Surgery and Critical Care, Network Development and Telehealth, University of Utah, Salt Lake City, US (Kimball); the Faculties of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium (Malbrain)
| | - Braedon MacDonald
- From the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Departments of Medicine and Engineering, University of Calgary, Calgary, Alta. (Kirkpatrick, Hamilton, McKee); the Departments of Critical Care Medicine and Medicine, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alta. (MacDonald); the Department of Surgical Sciences and Integrated Diagnostics, University of Genoa; Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy (Pelosi); Regional Trauma Services; Departments of Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (Ball); the Division of Vascular and Endovascular Surgery, Department of Surgery, University of Ottawa, Ottawa, Ont. (Roberts); the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Regional Trauma Services; Foothills Medical Centre; Departments of Engineering, Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (McBeth); the Departments of Trauma and Emergency Surgery, Pisa University Hospital, Pisa, Italy (Cocolini); the Departments of General, Emergency and Trauma Surgery, Bufalini Hospital, Cesena, Italy (Ansaloni); the Division of Trauma Surgery, University of Campinas, Campinas, São Paulo, Brazil (Peireira); the Department of Surgery, Letterkenny University Hospital, Letterkenny, Donegal, Ireland (Sugrue); the Paris Regional Medical Centre, Paris, Texas, United States (Campbell); the Departments of Surgery and Critical Care, Network Development and Telehealth, University of Utah, Salt Lake City, US (Kimball); the Faculties of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium (Malbrain)
| | - Paolo Pelosi
- From the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Departments of Medicine and Engineering, University of Calgary, Calgary, Alta. (Kirkpatrick, Hamilton, McKee); the Departments of Critical Care Medicine and Medicine, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alta. (MacDonald); the Department of Surgical Sciences and Integrated Diagnostics, University of Genoa; Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy (Pelosi); Regional Trauma Services; Departments of Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (Ball); the Division of Vascular and Endovascular Surgery, Department of Surgery, University of Ottawa, Ottawa, Ont. (Roberts); the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Regional Trauma Services; Foothills Medical Centre; Departments of Engineering, Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (McBeth); the Departments of Trauma and Emergency Surgery, Pisa University Hospital, Pisa, Italy (Cocolini); the Departments of General, Emergency and Trauma Surgery, Bufalini Hospital, Cesena, Italy (Ansaloni); the Division of Trauma Surgery, University of Campinas, Campinas, São Paulo, Brazil (Peireira); the Department of Surgery, Letterkenny University Hospital, Letterkenny, Donegal, Ireland (Sugrue); the Paris Regional Medical Centre, Paris, Texas, United States (Campbell); the Departments of Surgery and Critical Care, Network Development and Telehealth, University of Utah, Salt Lake City, US (Kimball); the Faculties of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium (Malbrain)
| | - Chad G Ball
- From the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Departments of Medicine and Engineering, University of Calgary, Calgary, Alta. (Kirkpatrick, Hamilton, McKee); the Departments of Critical Care Medicine and Medicine, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alta. (MacDonald); the Department of Surgical Sciences and Integrated Diagnostics, University of Genoa; Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy (Pelosi); Regional Trauma Services; Departments of Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (Ball); the Division of Vascular and Endovascular Surgery, Department of Surgery, University of Ottawa, Ottawa, Ont. (Roberts); the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Regional Trauma Services; Foothills Medical Centre; Departments of Engineering, Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (McBeth); the Departments of Trauma and Emergency Surgery, Pisa University Hospital, Pisa, Italy (Cocolini); the Departments of General, Emergency and Trauma Surgery, Bufalini Hospital, Cesena, Italy (Ansaloni); the Division of Trauma Surgery, University of Campinas, Campinas, São Paulo, Brazil (Peireira); the Department of Surgery, Letterkenny University Hospital, Letterkenny, Donegal, Ireland (Sugrue); the Paris Regional Medical Centre, Paris, Texas, United States (Campbell); the Departments of Surgery and Critical Care, Network Development and Telehealth, University of Utah, Salt Lake City, US (Kimball); the Faculties of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium (Malbrain)
| | - Derek Roberts
- From the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Departments of Medicine and Engineering, University of Calgary, Calgary, Alta. (Kirkpatrick, Hamilton, McKee); the Departments of Critical Care Medicine and Medicine, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alta. (MacDonald); the Department of Surgical Sciences and Integrated Diagnostics, University of Genoa; Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy (Pelosi); Regional Trauma Services; Departments of Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (Ball); the Division of Vascular and Endovascular Surgery, Department of Surgery, University of Ottawa, Ottawa, Ont. (Roberts); the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Regional Trauma Services; Foothills Medical Centre; Departments of Engineering, Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (McBeth); the Departments of Trauma and Emergency Surgery, Pisa University Hospital, Pisa, Italy (Cocolini); the Departments of General, Emergency and Trauma Surgery, Bufalini Hospital, Cesena, Italy (Ansaloni); the Division of Trauma Surgery, University of Campinas, Campinas, São Paulo, Brazil (Peireira); the Department of Surgery, Letterkenny University Hospital, Letterkenny, Donegal, Ireland (Sugrue); the Paris Regional Medical Centre, Paris, Texas, United States (Campbell); the Departments of Surgery and Critical Care, Network Development and Telehealth, University of Utah, Salt Lake City, US (Kimball); the Faculties of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium (Malbrain)
| | - Paul B McBeth
- From the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Departments of Medicine and Engineering, University of Calgary, Calgary, Alta. (Kirkpatrick, Hamilton, McKee); the Departments of Critical Care Medicine and Medicine, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alta. (MacDonald); the Department of Surgical Sciences and Integrated Diagnostics, University of Genoa; Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy (Pelosi); Regional Trauma Services; Departments of Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (Ball); the Division of Vascular and Endovascular Surgery, Department of Surgery, University of Ottawa, Ottawa, Ont. (Roberts); the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Regional Trauma Services; Foothills Medical Centre; Departments of Engineering, Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (McBeth); the Departments of Trauma and Emergency Surgery, Pisa University Hospital, Pisa, Italy (Cocolini); the Departments of General, Emergency and Trauma Surgery, Bufalini Hospital, Cesena, Italy (Ansaloni); the Division of Trauma Surgery, University of Campinas, Campinas, São Paulo, Brazil (Peireira); the Department of Surgery, Letterkenny University Hospital, Letterkenny, Donegal, Ireland (Sugrue); the Paris Regional Medical Centre, Paris, Texas, United States (Campbell); the Departments of Surgery and Critical Care, Network Development and Telehealth, University of Utah, Salt Lake City, US (Kimball); the Faculties of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium (Malbrain)
| | - Federico Cocolini
- From the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Departments of Medicine and Engineering, University of Calgary, Calgary, Alta. (Kirkpatrick, Hamilton, McKee); the Departments of Critical Care Medicine and Medicine, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alta. (MacDonald); the Department of Surgical Sciences and Integrated Diagnostics, University of Genoa; Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy (Pelosi); Regional Trauma Services; Departments of Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (Ball); the Division of Vascular and Endovascular Surgery, Department of Surgery, University of Ottawa, Ottawa, Ont. (Roberts); the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Regional Trauma Services; Foothills Medical Centre; Departments of Engineering, Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (McBeth); the Departments of Trauma and Emergency Surgery, Pisa University Hospital, Pisa, Italy (Cocolini); the Departments of General, Emergency and Trauma Surgery, Bufalini Hospital, Cesena, Italy (Ansaloni); the Division of Trauma Surgery, University of Campinas, Campinas, São Paulo, Brazil (Peireira); the Department of Surgery, Letterkenny University Hospital, Letterkenny, Donegal, Ireland (Sugrue); the Paris Regional Medical Centre, Paris, Texas, United States (Campbell); the Departments of Surgery and Critical Care, Network Development and Telehealth, University of Utah, Salt Lake City, US (Kimball); the Faculties of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium (Malbrain)
| | - Luca Ansaloni
- From the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Departments of Medicine and Engineering, University of Calgary, Calgary, Alta. (Kirkpatrick, Hamilton, McKee); the Departments of Critical Care Medicine and Medicine, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alta. (MacDonald); the Department of Surgical Sciences and Integrated Diagnostics, University of Genoa; Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy (Pelosi); Regional Trauma Services; Departments of Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (Ball); the Division of Vascular and Endovascular Surgery, Department of Surgery, University of Ottawa, Ottawa, Ont. (Roberts); the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Regional Trauma Services; Foothills Medical Centre; Departments of Engineering, Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (McBeth); the Departments of Trauma and Emergency Surgery, Pisa University Hospital, Pisa, Italy (Cocolini); the Departments of General, Emergency and Trauma Surgery, Bufalini Hospital, Cesena, Italy (Ansaloni); the Division of Trauma Surgery, University of Campinas, Campinas, São Paulo, Brazil (Peireira); the Department of Surgery, Letterkenny University Hospital, Letterkenny, Donegal, Ireland (Sugrue); the Paris Regional Medical Centre, Paris, Texas, United States (Campbell); the Departments of Surgery and Critical Care, Network Development and Telehealth, University of Utah, Salt Lake City, US (Kimball); the Faculties of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium (Malbrain)
| | - Bruno Peireira
- From the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Departments of Medicine and Engineering, University of Calgary, Calgary, Alta. (Kirkpatrick, Hamilton, McKee); the Departments of Critical Care Medicine and Medicine, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alta. (MacDonald); the Department of Surgical Sciences and Integrated Diagnostics, University of Genoa; Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy (Pelosi); Regional Trauma Services; Departments of Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (Ball); the Division of Vascular and Endovascular Surgery, Department of Surgery, University of Ottawa, Ottawa, Ont. (Roberts); the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Regional Trauma Services; Foothills Medical Centre; Departments of Engineering, Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (McBeth); the Departments of Trauma and Emergency Surgery, Pisa University Hospital, Pisa, Italy (Cocolini); the Departments of General, Emergency and Trauma Surgery, Bufalini Hospital, Cesena, Italy (Ansaloni); the Division of Trauma Surgery, University of Campinas, Campinas, São Paulo, Brazil (Peireira); the Department of Surgery, Letterkenny University Hospital, Letterkenny, Donegal, Ireland (Sugrue); the Paris Regional Medical Centre, Paris, Texas, United States (Campbell); the Departments of Surgery and Critical Care, Network Development and Telehealth, University of Utah, Salt Lake City, US (Kimball); the Faculties of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium (Malbrain)
| | - Michael Sugrue
- From the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Departments of Medicine and Engineering, University of Calgary, Calgary, Alta. (Kirkpatrick, Hamilton, McKee); the Departments of Critical Care Medicine and Medicine, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alta. (MacDonald); the Department of Surgical Sciences and Integrated Diagnostics, University of Genoa; Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy (Pelosi); Regional Trauma Services; Departments of Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (Ball); the Division of Vascular and Endovascular Surgery, Department of Surgery, University of Ottawa, Ottawa, Ont. (Roberts); the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Regional Trauma Services; Foothills Medical Centre; Departments of Engineering, Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (McBeth); the Departments of Trauma and Emergency Surgery, Pisa University Hospital, Pisa, Italy (Cocolini); the Departments of General, Emergency and Trauma Surgery, Bufalini Hospital, Cesena, Italy (Ansaloni); the Division of Trauma Surgery, University of Campinas, Campinas, São Paulo, Brazil (Peireira); the Department of Surgery, Letterkenny University Hospital, Letterkenny, Donegal, Ireland (Sugrue); the Paris Regional Medical Centre, Paris, Texas, United States (Campbell); the Departments of Surgery and Critical Care, Network Development and Telehealth, University of Utah, Salt Lake City, US (Kimball); the Faculties of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium (Malbrain)
| | - Mark R Campbell
- From the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Departments of Medicine and Engineering, University of Calgary, Calgary, Alta. (Kirkpatrick, Hamilton, McKee); the Departments of Critical Care Medicine and Medicine, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alta. (MacDonald); the Department of Surgical Sciences and Integrated Diagnostics, University of Genoa; Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy (Pelosi); Regional Trauma Services; Departments of Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (Ball); the Division of Vascular and Endovascular Surgery, Department of Surgery, University of Ottawa, Ottawa, Ont. (Roberts); the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Regional Trauma Services; Foothills Medical Centre; Departments of Engineering, Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (McBeth); the Departments of Trauma and Emergency Surgery, Pisa University Hospital, Pisa, Italy (Cocolini); the Departments of General, Emergency and Trauma Surgery, Bufalini Hospital, Cesena, Italy (Ansaloni); the Division of Trauma Surgery, University of Campinas, Campinas, São Paulo, Brazil (Peireira); the Department of Surgery, Letterkenny University Hospital, Letterkenny, Donegal, Ireland (Sugrue); the Paris Regional Medical Centre, Paris, Texas, United States (Campbell); the Departments of Surgery and Critical Care, Network Development and Telehealth, University of Utah, Salt Lake City, US (Kimball); the Faculties of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium (Malbrain)
| | - Edward J Kimball
- From the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Departments of Medicine and Engineering, University of Calgary, Calgary, Alta. (Kirkpatrick, Hamilton, McKee); the Departments of Critical Care Medicine and Medicine, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alta. (MacDonald); the Department of Surgical Sciences and Integrated Diagnostics, University of Genoa; Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy (Pelosi); Regional Trauma Services; Departments of Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (Ball); the Division of Vascular and Endovascular Surgery, Department of Surgery, University of Ottawa, Ottawa, Ont. (Roberts); the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Regional Trauma Services; Foothills Medical Centre; Departments of Engineering, Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (McBeth); the Departments of Trauma and Emergency Surgery, Pisa University Hospital, Pisa, Italy (Cocolini); the Departments of General, Emergency and Trauma Surgery, Bufalini Hospital, Cesena, Italy (Ansaloni); the Division of Trauma Surgery, University of Campinas, Campinas, São Paulo, Brazil (Peireira); the Department of Surgery, Letterkenny University Hospital, Letterkenny, Donegal, Ireland (Sugrue); the Paris Regional Medical Centre, Paris, Texas, United States (Campbell); the Departments of Surgery and Critical Care, Network Development and Telehealth, University of Utah, Salt Lake City, US (Kimball); the Faculties of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium (Malbrain)
| | - Manu L N G Malbrain
- From the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Departments of Medicine and Engineering, University of Calgary, Calgary, Alta. (Kirkpatrick, Hamilton, McKee); the Departments of Critical Care Medicine and Medicine, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alta. (MacDonald); the Department of Surgical Sciences and Integrated Diagnostics, University of Genoa; Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy (Pelosi); Regional Trauma Services; Departments of Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (Ball); the Division of Vascular and Endovascular Surgery, Department of Surgery, University of Ottawa, Ottawa, Ont. (Roberts); the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Regional Trauma Services; Foothills Medical Centre; Departments of Engineering, Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (McBeth); the Departments of Trauma and Emergency Surgery, Pisa University Hospital, Pisa, Italy (Cocolini); the Departments of General, Emergency and Trauma Surgery, Bufalini Hospital, Cesena, Italy (Ansaloni); the Division of Trauma Surgery, University of Campinas, Campinas, São Paulo, Brazil (Peireira); the Department of Surgery, Letterkenny University Hospital, Letterkenny, Donegal, Ireland (Sugrue); the Paris Regional Medical Centre, Paris, Texas, United States (Campbell); the Departments of Surgery and Critical Care, Network Development and Telehealth, University of Utah, Salt Lake City, US (Kimball); the Faculties of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium (Malbrain)
| | - Derek Roberts
- From the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Departments of Medicine and Engineering, University of Calgary, Calgary, Alta. (Kirkpatrick, Hamilton, McKee); the Departments of Critical Care Medicine and Medicine, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alta. (MacDonald); the Department of Surgical Sciences and Integrated Diagnostics, University of Genoa; Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy (Pelosi); Regional Trauma Services; Departments of Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (Ball); the Division of Vascular and Endovascular Surgery, Department of Surgery, University of Ottawa, Ottawa, Ont. (Roberts); the Tele-Mentored Ultrasound Supported Medical Interventions (TMUSMI) Research Group Collaborators; Regional Trauma Services; Foothills Medical Centre; Departments of Engineering, Surgery and Critical Care Medicine, University of Calgary, Calgary, Alta. (McBeth); the Departments of Trauma and Emergency Surgery, Pisa University Hospital, Pisa, Italy (Cocolini); the Departments of General, Emergency and Trauma Surgery, Bufalini Hospital, Cesena, Italy (Ansaloni); the Division of Trauma Surgery, University of Campinas, Campinas, São Paulo, Brazil (Peireira); the Department of Surgery, Letterkenny University Hospital, Letterkenny, Donegal, Ireland (Sugrue); the Paris Regional Medical Centre, Paris, Texas, United States (Campbell); the Departments of Surgery and Critical Care, Network Development and Telehealth, University of Utah, Salt Lake City, US (Kimball); the Faculties of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium (Malbrain)
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Erbil Y, Berber E, Seven R, Çaliş A, Eminoğlu L, Koçak M, Bilgiç L. The Effect of Intestinal Transit Time on Bacterial Translocation. Acta Chir Belg 2020. [DOI: 10.1080/00015458.1998.12098425] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Affiliation(s)
- Y. Erbil
- Departments of Surgery, University of Istanbul, Istanbul School of Medicine, Turkey
| | - E. Berber
- Departments of Surgery, University of Istanbul, Istanbul School of Medicine, Turkey
| | - R. Seven
- Departments of Surgery, University of Istanbul, Istanbul School of Medicine, Turkey
| | - A. Çaliş
- Departments of Surgery, University of Istanbul, Istanbul School of Medicine, Turkey
| | - L. Eminoğlu
- Departments of Nuclear Medicine, University of Istanbul, Istanbul School of Medicine, Turkey
| | - M. Koçak
- Departments of Nuclear Medicine, University of Istanbul, Istanbul School of Medicine, Turkey
| | - L. Bilgiç
- Departments of Pathology, University of Istanbul, Istanbul School of Medicine, Turkey
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Stewart RH. A Modern View of the Interstitial Space in Health and Disease. Front Vet Sci 2020; 7:609583. [PMID: 33251275 PMCID: PMC7674635 DOI: 10.3389/fvets.2020.609583] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Accepted: 10/14/2020] [Indexed: 12/15/2022] Open
Abstract
Increases in the volume of the interstitial space are readily recognized clinically as interstitial edema formation in the loose connective tissue of skin, mucosa, and lung. However, the contents and the hydrostatic pressure of this interstitial fluid can be very difficult to determine even in experimental settings. These difficulties have long obscured what we are beginning to appreciate is a dynamic milieu that is subject to both intrinsic and extrinsic regulation. This review examines current concepts regarding regulation of interstitial volume, pressure, and flow and utilizes that background to address three major topics of interest that impact IV fluid administration. The first of these started with the discovery that excess dietary salt can be stored non-osmotically in the interstitial space with minimal impact on vascular volume and pressures. This led to the hypothesis that, along with the kidney, the interstitial space plays an active role in the long-term regulation of blood pressure. Second, it now appears that hypovolemic shock leads to systemic inflammatory response syndrome principally through the entry of digestive enzymes into the intestinal interstitial space and the subsequent progression of enzymes and inflammatory agents through the mesenteric lymphatic system to the general circulation. Lastly, current evidence strongly supports the non-intuitive view that the primary factor leading to inflammatory edema formation is a decrease in interstitial hydrostatic pressure that dramatically increases microvascular filtration.
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Affiliation(s)
- Randolph H Stewart
- Department of Veterinary Physiology and Pharmacology, Michael E. DeBakey Institute, Texas A&M University, College Station, TX, United States
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Uzzan M, Corcos O, Martin JC, Treton X, Bouhnik Y. Why is SARS-CoV-2 infection more severe in obese men? The gut lymphatics - Lung axis hypothesis. Med Hypotheses 2020; 144:110023. [PMID: 32593832 PMCID: PMC7308746 DOI: 10.1016/j.mehy.2020.110023] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Accepted: 06/19/2020] [Indexed: 02/07/2023]
Abstract
Consistent observations report increased severity of SARS-CoV-2 infection in overweight men with cardiovascular factors. As the visceral fat possesses an intense immune activity, is involved in metabolic syndrome and is at the crossroad between the intestines, the systemic circulation and the lung, we hypothesized that it plays a major role in severe forms of SARS-CoV-2 infection. SARS-CoV2 presents the ability to infect epithelial cells of the respiratory tract as well as the intestinal tract. Several factors may increase intestinal permeability including direct enterocyte damage by SARS-CoV2, systemic inflammatory response syndrome (SIRS) and epithelial ischemia secondary to SARS-CoV2- associated endothelial dysfunction. This increase permeability further leads to translocation of microbial components such as MAMPs (microbial-associated molecular pattern), triggering an inflammatory immune response by TLR-expressing cells of the mesentery fat (mostly macrophages and adipocytes). The pro-inflammatory cytokines produced by the mesentery fat mediates systemic inflammation and aggravate acute respiratory distress syndrome (ARDS) through the mesenteric lymph drainage.
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Affiliation(s)
- Mathieu Uzzan
- Department of Gastroenterology, IBD and Nutritional Support, CHU Paris Nord-Val de Seine, Beaujon Hospital, Clichy, France.
| | - Olivier Corcos
- Department of Gastroenterology, IBD and Nutritional Support, CHU Paris Nord-Val de Seine, Beaujon Hospital, Clichy, France
| | - Jerome C Martin
- Université de Nantes, Inserm, CHU Nantes, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, F-44000 Nantes, France; CHU Nantes, Laboratoire d'Immunologie, Center for Immuno Monitoring Nantes-Atlantique (CIMNA), F-44000 Nantes, France
| | - Xavier Treton
- Department of Gastroenterology, IBD and Nutritional Support, CHU Paris Nord-Val de Seine, Beaujon Hospital, Clichy, France
| | - Yoram Bouhnik
- Department of Gastroenterology, IBD and Nutritional Support, CHU Paris Nord-Val de Seine, Beaujon Hospital, Clichy, France
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Mesenteric Lymph Duct Drainage Attenuates Lung Inflammatory Injury and Inhibits Endothelial Cell Apoptosis in Septic Rats. BIOMED RESEARCH INTERNATIONAL 2020; 2020:3049302. [PMID: 33145344 PMCID: PMC7596461 DOI: 10.1155/2020/3049302] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 08/06/2020] [Accepted: 08/13/2020] [Indexed: 01/19/2023]
Abstract
The present study was to investigate the effect of mesenteric lymph duct drainage on lung inflammatory response, histological alteration, and endothelial cell apoptosis in septic rats. Animals were randomly assigned into four groups: control, sham surgery, sepsis, and sepsis plus mesenteric lymph drainage. We used the colon ascendens stent peritonitis (CASP) procedure to induce the septic model in rats, and mesenteric lymph drainage was performed with a polyethylene (PE) catheter inserted into mesenteric lymphatic. The animals were sacrificed at the end of CASP in 6 h. The mRNA expression levels of inflammatory mediators were measured by qPCR, and the histologic damage were evaluated by the pathological score method. It was found that mesenteric lymph drainage significantly reduced the expression of TNF-α, IL-1β, and IL-6 mRNA in the lung. Pulmonary interstitial edema and infiltration of inflammatory cells were alleviated by mesenteric lymph drainage. Moreover, increased mRNA levels of TNF-α, IL-1β, IL-6 mRNA, and apoptotic rate were observed in PMVECs treated with septic lymph. These results indicate that mesenteric lymph duct drainage significantly attenuated lung inflammatory injury by decreasing the expression of pivotal inflammatory mediators and inhibiting endothelial apoptosis to preserve the pulmonary barrier function in septic rats.
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Abstract
Dysfunction of the gut-blood barrier plays an important role in many diseases, such as inflammatory bowel disease, hemorrhagic shock (HS), or burn injury. However, little is known about gut barrier dysfunction after hemodynamically instable polytrauma (PT). Therefore, we aimed to evaluate the effects of PT and HS on remote intestinal damage and barrier dysfunction, especially regarding the role of zonula occludens protein 1 (ZO-1) as an important tight junction protein.Male C57BL/6 mice were subjected to either PT (thorax trauma, closed head injury, soft tissue injury, and distal femoral fracture), 60 min of pressure-controlled HS (30 ± 5 mmHg), or PT+HS, or sham procedures.Animals of all trauma groups showed an increase in abdominal girth and dilation of the intestine during the experimental period, which was largest in the PT+HS group. Increased blood-tissue permeability to albumin (assessed by Evans blue dye) was found in the HS group. Experimental groups showed a slight increase in plasma concentration of intestinal fatty acid binding protein and some intestinal damage was histologically detectable. Of note, PT+HS animals revealed significantly reduced expression of ZO-1 in intestinal epithelial cells. In an in-vitro model, stimulation of human colon epithelial cells with peptidoglycan, but not with lipopolysaccharide, resulted in elevated secretion of pro-inflammatory cytokines, reflecting inflammatory activity of the intestinal epithelium.Taken together, PT and HS lead to increased permeability of the gut-blood barrier. Bacterial components may lead to production of inflammatory and chemotactic mediators by gut epithelial cells, underlining the role of the gut as an immunologically active organ.
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Ashammakhi N, Darabi MA, Çelebi-Saltik B, Tutar R, Hartel MC, Lee J, Hussein S, Goudie MJ, Cornelius MB, Dokmeci MR, Khademhosseini A. Microphysiological Systems: Next Generation Systems for Assessing Toxicity and Therapeutic Effects of Nanomaterials. SMALL METHODS 2020; 4:1900589. [PMID: 33043130 PMCID: PMC7546538 DOI: 10.1002/smtd.201900589] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Indexed: 05/27/2023]
Abstract
Microphysiological systems, also known as organ-on-a-chip platforms, show promise for the development of new testing methods that can be more accurate than both conventional two-dimensional cultures and costly animal studies. The development of more intricate microphysiological systems can help to better mimic the human physiology and highlight the systemic effects of different drugs and materials. Nanomaterials are among a technologically important class of materials used for diagnostic, therapeutic, and monitoring purposes; all of which and can be tested using new organ-on-a-chip systems. In addition, the toxicity of nanomaterials which have entered the body from ambient air or diet can have deleterious effects on various body systems. This in turn can be studied in newly developed microphysiological systems. While organ-on-a-chip models can be useful, they cannot pick up secondary and systemic toxicity. Thus, the utilization of multi-organ-on-a-chip systems for advancing nanotechnology will largely be reflected in the future of drug development, toxicology studies and precision medicine. Various aspects of related studies, current challenges, and future perspectives are discussed in this paper.
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Affiliation(s)
- Nureddin Ashammakhi
- Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, California, USA
- Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, California, USA
- California NanoSystems Institute (CNSI), University of California, Los Angeles, California, USA
- Department of Bioengineering, University of California, Los Angeles, California, USA
| | - Mohammad Ali Darabi
- Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, California, USA
- Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, California, USA
- Department of Bioengineering, University of California, Los Angeles, California, USA
| | - Betül Çelebi-Saltik
- Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, California, USA
- Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, California, USA
- Department of Bioengineering, University of California, Los Angeles, California, USA
- Department of Stem Cell Sciences, Hacettepe University Graduate School of Health Sciences, 06100, Sihhiye, Ankara, Turkey
| | - Rumeysa Tutar
- Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, California, USA
- Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, California, USA
- Department of Bioengineering, University of California, Los Angeles, California, USA
- Department of Chemistry, Faculty of Engineering, Istanbul University Cerrahpasa, Avcilar-Istanbul, Turkey
| | - Martin C. Hartel
- Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, California, USA
- Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, California, USA
- California NanoSystems Institute (CNSI), University of California, Los Angeles, California, USA
| | - Junmin Lee
- Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, California, USA
- Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, California, USA
- Department of Bioengineering, University of California, Los Angeles, California, USA
| | - Saber Hussein
- Wright State University, Boonshoft School of Medicine, 3640 Colonel Glenn Hwy, Dayton, OH 45435, Ohio, USA
| | - Marcus J. Goudie
- Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, California, USA
- Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, California, USA
- Department of Bioengineering, University of California, Los Angeles, California, USA
| | - Mercedes Brianna Cornelius
- California NanoSystems Institute (CNSI), University of California, Los Angeles, California, USA
- Department of Chemistry, University of California, Los Angeles, California, USA
| | - Mehmet R. Dokmeci
- Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, California, USA
- Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, California, USA
- California NanoSystems Institute (CNSI), University of California, Los Angeles, California, USA
| | - Ali Khademhosseini
- Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, California, USA
- Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles, California, USA
- California NanoSystems Institute (CNSI), University of California, Los Angeles, California, USA
- Department of Bioengineering, University of California, Los Angeles, California, USA
- Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095, USA
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Amornphimoltham P, Yuen PST, Star RA, Leelahavanichkul A. Gut Leakage of Fungal-Derived Inflammatory Mediators: Part of a Gut-Liver-Kidney Axis in Bacterial Sepsis. Dig Dis Sci 2019; 64:2416-2428. [PMID: 30863955 DOI: 10.1007/s10620-019-05581-y] [Citation(s) in RCA: 66] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Accepted: 03/06/2019] [Indexed: 02/07/2023]
Abstract
Sepsis is a life-threatening response to systemic infection. In addition to frank gastrointestinal (GI) rupture/puncture, sepsis can also be exacerbated by translocation of pathogen-associated molecular patterns (PAMPs) from the GI tract to the systemic circulation (gut origin of sepsis). In the human gut, Gram-negative bacteria and Candida albicans are abundant, along with their major PAMP components, endotoxin (LPS) and (1 → 3)-β-D-glucan (BG). Whereas the influence of LPS in bacterial sepsis has been studied extensively, exploration of the role of BG in bacterial sepsis is limited. Post-translocation, PAMPs enter the circulation through lymphatics and the portal vein, and are detoxified and then excreted via the liver and the kidney. Sepsis-induced liver and kidney injury might therefore affect the kinetics and increase circulating PAMPs. In this article, we discuss the current knowledge of the impact of PAMPs from both gut mycobiota and microbiota, including epithelial barrier function and the "gut-liver-kidney axis," on bacterial sepsis severity.
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Affiliation(s)
| | - Peter S T Yuen
- Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Robert A Star
- Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Asada Leelahavanichkul
- Immunology Unit, Department of Microbiology, Chulalongkorn University, Bangkok, 10330, Thailand. .,Center of Excellence in Immunology and Immune-mediated Diseases, Department of Microbiology, Chulalongkorn University, Bangkok, Thailand.
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28
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Abstract
Multiple organ dysfunction syndrome (MODS) is one of the most common syndromes of critical illness and the leading cause of mortality among critically ill patients. Multiple organ dysfunction syndrome is the clinical consequence of a dysregulated inflammatory response, triggered by clinically diverse factors with the main pillar of management being invasive organ support. During the last years, the advances in the clarification of the molecular pathways that trigger, mitigate, and determine the outcome of MODS have led to the increasing recognition of MODS as a distinct disease entity with distinct etiology, pathophysiology, and potential future therapeutic interventions. Given the lack of effective treatment for MODS, its early recognition, the early intensive care unit admission, and the initiation of invasive organ support remain the most effective strategies of preventing its progression and improving outcomes.
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Affiliation(s)
- Nicholas M Gourd
- Department of Intensive Care Medicine, Derriford Hospital, 6634University Hospitals Plymouth NHS Trust, Plymouth, United Kingdom.,Faculty of Medicine and Dentistry, 6634University of Plymouth, Plymouth, United Kingdom
| | - Nikitas Nikitas
- Department of Intensive Care Medicine, Derriford Hospital, 6634University Hospitals Plymouth NHS Trust, Plymouth, United Kingdom
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Wise AK, Hromatka KA, Miller KR. Energy Expenditure and Protein Requirements Following Burn Injury. Nutr Clin Pract 2019; 34:673-680. [PMID: 31418486 DOI: 10.1002/ncp.10390] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Severe burn injuries have long been known to have a profound effect on metabolic equilibrium that can persist after resolution of the cutaneous injuries. Following burn injury, metabolism is a dynamic state resulting in the need for frequent interval reassessment over the course of the care continuum. The acute phase of injury transitions to chronic alterations in macronutrient utilization characterized by futile energy cycling and disproportionate catabolism of skeletal muscle. Protein supplementation appears to be preferentially distributed to the burn wound rather than the skeletal muscle pool. Accurate assessment of caloric and protein requirements is extremely difficult in these patients but is an essential step in efforts to attenuate functional impairment. Indirect calorimetry should be utilized to determine caloric requirements, but trophic feeding strategies are preferred in the initial resuscitative phase to prevent overfeeding while maintaining enteric and immune function. Controversy persists regarding optimal protein targets, and weight-based estimates remain the norm. Exogenous protein and caloric provision performed in isolation is insufficient to optimize outcomes and should be incorporated within a multidisciplinary approach to include muscle loading and pharmaceutical adjuncts.
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Affiliation(s)
- Amy K Wise
- Department of Surgery, University of Louisville, Louisville, Kentucky, USA
| | | | - Keith R Miller
- Department of Surgery, University of Louisville, Louisville, Kentucky, USA
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30
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Lu F, Inoue K, Kato J, Minamishima S, Morisaki H. Functions and regulation of lipocalin-2 in gut-origin sepsis: a narrative review. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2019; 23:269. [PMID: 31375129 PMCID: PMC6679544 DOI: 10.1186/s13054-019-2550-2] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Accepted: 07/22/2019] [Indexed: 12/14/2022]
Abstract
Lipocalin-2 (Lcn2), an innate immune protein, has come to be recognized for its roles in iron homeostasis, infection, and inflammation. In this narrative review, we provide a comprehensive description based on currently available evidence of the clinical implications of Lcn2 and its therapeutic potency in gut-origin sepsis. Lcn2 appears to mitigate gut barrier injury via maintaining homeostasis of the microbiota and exerting antioxidant strategy, as well as by deactivating macrophages and inducing immune cell apoptosis to terminate systemic hyper-inflammation. We propose that development of a therapeutic strategy targeting lipocalin-2 could be highly promising in the management of gut-origin sepsis.
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Affiliation(s)
- Fanglin Lu
- Keio University Graduate School of Medicine Doctoral Programs, Tokyo, Japan.,Department of Anesthesiology, Keio University School of Medicine, 35 Shinanoamchi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Kei Inoue
- Department of Anesthesiology, Keio University School of Medicine, 35 Shinanoamchi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Jungo Kato
- Department of Anesthesiology, Keio University School of Medicine, 35 Shinanoamchi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Shizuka Minamishima
- Department of Anesthesiology, Keio University School of Medicine, 35 Shinanoamchi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Hiroshi Morisaki
- Department of Anesthesiology, Keio University School of Medicine, 35 Shinanoamchi, Shinjuku-ku, Tokyo, 160-8582, Japan.
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31
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van Ruissen MCE, Bos LD, Dickson RP, Dondorp AM, Schultsz C, Schultz MJ. Manipulation of the microbiome in critical illness-probiotics as a preventive measure against ventilator-associated pneumonia. Intensive Care Med Exp 2019; 7:37. [PMID: 31346841 PMCID: PMC6658628 DOI: 10.1186/s40635-019-0238-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 03/07/2019] [Indexed: 12/26/2022] Open
Abstract
Objective To describe the possible modes of action of probiotics and provide a systematic review of the current evidence on the efficacy of probiotics to prevent ventilator-associated pneumonia (VAP) in critically ill patients. Methods We conducted an unrestricted search of the English language medical literature. For each individual study, the relative risk of VAP was calculated using the reported primary outcome data. Results The search identified a total of 72 articles. Eight articles enrolling a total of 1229 patients fulfilled the inclusion and exclusion criteria. In four trials, the investigators were blinded for the intervention, and two trials used an intention-to-treat analysis. Loss to follow-up with regard to the primary endpoint ranged from 0 to 14% in the intervention groups and from 0 to 16% in the control groups. The incidence of VAP expressed as the percentage of studied patients was reported in seven trials. The incidence of VAP ranged from 4 to 36% in the intervention groups and from 13 to 50% in the control groups. The relative risk for VAP ranged between 0.30 and 1.41. Three trials showed a significant difference in favor of probiotic therapy between the intervention and the control groups. Conclusions The incidence of VAP tended to be lower in patients treated with probiotics in most trials identified by the systematic search. Due to the heterogeneity of the studies and the low quality of evidence, it remains difficult to draw firm conclusions. The efficacy of preventive probiotics should be studied in more detail in future trials. Application of probiotics for the prevention of VAP seems to be safe with only few side effects reported in the selected trials. Electronic supplementary material The online version of this article (10.1186/s40635-019-0238-1) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Marel C E van Ruissen
- Amsterdam Institute for Global Health and Development (AIGHD), Academic Medical Center, Amsterdam, The Netherlands
| | - Lieuwe D Bos
- Department of Pulmonology, Academic Medical Center, Amsterdam, The Netherlands. .,Department of Intensive Care, Academic Medical Center, C3-425, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
| | - Robert P Dickson
- Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Arjen M Dondorp
- Department of Intensive Care, Academic Medical Center, C3-425, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.,Mahidol Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand
| | - Constance Schultsz
- Amsterdam Institute for Global Health and Development (AIGHD), Academic Medical Center, Amsterdam, The Netherlands
| | - Marcus J Schultz
- Department of Intensive Care, Academic Medical Center, C3-425, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.,Mahidol Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand.,Laboratory of Experimental Intensive Care and Anesthesiology (L·E·I·C·A), Academic Medical Center, Amsterdam, The Netherlands
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32
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Panzer AR, Lynch SV, Langelier C, Christie JD, McCauley K, Nelson M, Cheung CK, Benowitz NL, Cohen MJ, Calfee CS. Lung Microbiota Is Related to Smoking Status and to Development of Acute Respiratory Distress Syndrome in Critically Ill Trauma Patients. Am J Respir Crit Care Med 2019; 197:621-631. [PMID: 29035085 DOI: 10.1164/rccm.201702-0441oc] [Citation(s) in RCA: 104] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
RATIONALE Cigarette smoking is associated with increased risk of acute respiratory distress syndrome (ARDS) in patients after severe trauma; however, the mechanisms underlying this association are unknown. OBJECTIVES To determine whether cigarette smoking contributes to ARDS development after trauma by altering community composition of the lung microbiota. METHODS We studied the lung microbiota of mechanically ventilated patients admitted to the ICU after severe blunt trauma. To do so, we used 16S ribosomal RNA gene amplicon sequencing of endotracheal aspirate samples obtained on ICU admission (n = 74) and at 48 hours after admission (n = 30). Cigarette smoke exposure (quantified using plasma cotinine), ARDS development, and other clinical parameters were correlated with lung microbiota composition. MEASUREMENTS AND MAIN RESULTS Smoking status was significantly associated with lung bacterial community composition at ICU admission (P = 0.007 by permutational multivariate ANOVA [PERMANOVA]) and at 48 hours (P = 0.03 by PERMANOVA), as well as with significant enrichment of potential pathogens, including Streptococcus, Fusobacterium, Prevotella, Haemophilus, and Treponema. ARDS development was associated with lung community composition at 48 hours (P = 0.04 by PERMANOVA) and was characterized by relative enrichment of Enterobacteriaceae and of specific taxa enriched at baseline in smokers, including Prevotella and Fusobacterium. CONCLUSIONS After severe blunt trauma, a history of smoking is related to lung microbiota composition, both at the time of ICU admission and at 48 hours. ARDS development is also correlated with respiratory microbial community structure at 48 hours and with taxa that are relatively enriched in smokers at ICU admission. The data derived from this pilot study suggest that smoking-related changes in the lung microbiota could be related to ARDS development after severe trauma.
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Affiliation(s)
| | - Susan V Lynch
- 1 Division of Gastroenterology, Department of Medicine
| | - Chaz Langelier
- 2 Division of Infectious Diseases, Department of Medicine
| | - Jason D Christie
- 3 Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | | | - Mary Nelson
- 4 Department of Surgery.,5 Zuckerberg San Francisco General Hospital, San Francisco, California
| | - Christopher K Cheung
- 4 Department of Surgery.,5 Zuckerberg San Francisco General Hospital, San Francisco, California
| | - Neal L Benowitz
- 6 Division of Clinical Pharmacology, Department of Medicine.,5 Zuckerberg San Francisco General Hospital, San Francisco, California
| | - Mitchell J Cohen
- 7 Department of Surgery, Denver Health Medical Center, Denver, Colorado; and.,8 Department of Surgery, University of Colorado, Aurora, Colorado
| | - Carolyn S Calfee
- 9 Division of Pulmonary and Critical Care Medicine, Department of Medicine.,10 Department of Anesthesia.,11 Cardiovascular Research Institute, and.,12 Center for Tobacco Control Research and Education, University of California, San Francisco, San Francisco, California
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Abstract
PURPOSE OF REVIEW Gastrointestinal dysmotility occurs frequently in the critically ill. Although the causes underlying dysmotility are multifactorial, both pain and its treatment with exogenous opioids are likely causative factors. The purpose of this review is to describe the effects of pain and opioids on gastrointestinal motility; outline the rationale for and evidence supporting the administration of opioid antagonists to improve dysmotility; and describe the potential influence opioids drugs have on the intestinal microbiome and infectious complications. RECENT FINDINGS Opioid drugs are frequently prescribed in the critically ill to alleviate pain. In health, opioids cause gastric dysmotility, yet the evidence for this in critical illness is inconsistent and limited to observational studies. Administration of opioid antagonists may improve gastrointestinal motility, but data are sparse, and these agents cannot be recommended outside of clinical trials. Although critical illness is associated with alterations in the microbiome, the extent to which opioid administration influences these changes, and the subsequent development of infection, remains uncertain. SUMMARY Replication of clinical studies from ambulant populations in critical care is required to ascertain the independent influence of opioid administration on gastrointestinal motility and infectious complications.
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Haussner F, Chakraborty S, Halbgebauer R, Huber-Lang M. Challenge to the Intestinal Mucosa During Sepsis. Front Immunol 2019; 10:891. [PMID: 31114571 PMCID: PMC6502990 DOI: 10.3389/fimmu.2019.00891] [Citation(s) in RCA: 132] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Accepted: 04/08/2019] [Indexed: 12/12/2022] Open
Abstract
Sepsis is a complex of life-threating organ dysfunction in critically ill patients, with a primary infectious cause or through secondary infection of damaged tissues. The systemic consequences of sepsis have been intensively examined and evidences of local alterations and repercussions in the intestinal mucosal compartment is gradually defining gut-associated changes during sepsis. In the present review, we focus on sepsis-induced dysfunction of the intestinal barrier, consisting of an increased permeability of the epithelial lining, which may facilitate bacterial translocation. We discuss disturbances in intestinal vascular tonus and perfusion and coagulopathies with respect to their proposed underlying molecular mechanisms. The consequences of enzymatic responses by pancreatic proteases, intestinal alkaline phosphatases, and several matrix metalloproteases are also described. We conclude our insight with a discussion on novel therapeutic interventions derived from crucial aspects of the gut mucosal dynamics during sepsis.
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Affiliation(s)
- Felix Haussner
- Institute of Clinical and Experimental Trauma-Immunology, University Hospital of Ulm, Ulm, Germany
| | - Shinjini Chakraborty
- Institute of Clinical and Experimental Trauma-Immunology, University Hospital of Ulm, Ulm, Germany
| | - Rebecca Halbgebauer
- Institute of Clinical and Experimental Trauma-Immunology, University Hospital of Ulm, Ulm, Germany
| | - Markus Huber-Lang
- Institute of Clinical and Experimental Trauma-Immunology, University Hospital of Ulm, Ulm, Germany
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35
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Direct peritoneal resuscitation reduces intestinal permeability after brain death. J Trauma Acute Care Surg 2019; 84:265-272. [PMID: 29194322 DOI: 10.1097/ta.0000000000001742] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND The profound inflammatory response associated with brain death is frequently cited as the reason organs procured from brain dead donors are associated with worse graft function. The intestine releases inflammatory mediators in other types of shock, but its role is brain death has not been well-studied. Direct peritoneal resuscitation (DPR) improves visceral organ blood flow and reduces inflammation after hemorrhagic shock. We hypothesized that use of DPR would maintain intestinal integrity and reduce circulating inflammatory mediators after brain death. METHODS Brain death was induced in male Sprague-Dawley rats by inserting a 4F Fogarty catheter into the epidural space and slowly inflating it. After herniation, rats were resuscitated with normal saline to maintain a mean arterial pressure of 80 mm Hg and killed with tissue collected immediately (time 0), or 2 hours, 4 hours, or 6 hours after brain death. Randomly selected animals received DPR via an intraperitoneal injection of 30-mL commercial peritoneal dialysis solution. RESULTS Levels of proinflammatory cytokines, including IL-1β and IL-6, as well as high-mobility group box 1 protein and heat shock protein 70, were all increased after brain death and decreased with DPR. Fatty acid binding protein and lipopolysaccharide, both markers of intestinal injury, were increased in the serum after brain death and decreased with DPR. Immunohistochemistry staining for zona occludin-1 showed decreased intestinal tight junction integrity after brain death, which improved with DPR. CONCLUSIONS Intestinal permeability increases after brain death, and this contributes to the increased inflammation seen throughout the body. Using DPR prevents intestinal ischemia and helps preserve intestinal integrity. This suggests that using this novel therapy as an adjunct to the resuscitation of brain dead donors has the potential to reduce inflammation and potentially improve the quality of transplanted organs.
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Assimakopoulos SF, Triantos C, Thomopoulos K, Fligou F, Maroulis I, Marangos M, Gogos CA. Gut-origin sepsis in the critically ill patient: pathophysiology and treatment. Infection 2018; 46:751-760. [PMID: 30003491 DOI: 10.1007/s15010-018-1178-5] [Citation(s) in RCA: 145] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2018] [Accepted: 07/06/2018] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Gut permeability is increased in critically ill patients, and associated with the development of the systemic inflammatory response syndrome and multiple organ dysfunction syndrome (MODS). The pathogenetic link(s) and potential therapies are an area of intense research over the last decades. METHODS We thoroughly reviewed the literature on gut-origin sepsis and MODS in critically ill patients, with emphasis on the implicated pathophysiological mechanisms and therapeutic interventions. FINDINGS Intestinal barrier failure leading to systemic bacterial translocation associated with MODS was the predominant pathophysiological theory for several years. However, clinical studies with critically ill patients failed to provide the evidence of systemic spread of gut-derived bacteria and/or their products as a cause of MODS. Newer experimental data highlight the role of the mesenteric lymph as a carrier of gut-derived danger-associated molecular patterns (DAMPs) to the lung and the systemic circulation. These substances are recognized by pattern recognition receptor-bearing cells in diverse tissues and promote proinflammatory pathways and the development MODS. Therefore, the gut becomes a pivotal proinflammatory organ, driving the systemic inflammatory response through DAMPs release in mesenteric lymph, without the need for systemic bacterial translocation. CONCLUSIONS There is an emerging need for application of sensitive non-invasive and easily measured biomarkers of early intestinal injury (e.g., citrulline, intestinal fatty acid protein, and zonulin) in our everyday clinical practice, guiding the early pharmacological intervention in critically ill patients to restore or prevent intestinal injury and improve their outcomes.
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Affiliation(s)
- Stelios F Assimakopoulos
- Department of Internal Medicine, Division of Infectious Diseases, University of Patras Medical School, 26504, Patras, Greece.
| | - Christos Triantos
- Department of Internal Medicine, Division of Gastroenterology, University of Patras Medical School, 26504, Patras, Greece
| | - Konstantinos Thomopoulos
- Department of Internal Medicine, Division of Gastroenterology, University of Patras Medical School, 26504, Patras, Greece
| | - Fotini Fligou
- Department of Anesthesiology and Critical Care Medicine, University of Patras Medical School, 26504, Patras, Greece
| | - Ioannis Maroulis
- Department of Surgery, University of Patras Medical School, 26504, Patras, Greece
| | - Markos Marangos
- Department of Internal Medicine, Division of Infectious Diseases, University of Patras Medical School, 26504, Patras, Greece
| | - Charalambos A Gogos
- Department of Internal Medicine, Division of Infectious Diseases, University of Patras Medical School, 26504, Patras, Greece
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Moore EE. Trauma research: Trials and tribulations of a triceratops. J Trauma Acute Care Surg 2018; 85:841-850. [PMID: 30359335 DOI: 10.1097/ta.0000000000002054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- Ernest E Moore
- From the Departments of Surgery (E.E.M.), Ernest E Moore Shock Trauma Center at Denver Health and University of Colorado Denver, Denver, Colorado
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Danger signals from mitochondrial DAMPS in trauma and post-injury sepsis. Eur J Trauma Emerg Surg 2018; 44:317-324. [PMID: 29797026 DOI: 10.1007/s00068-018-0963-2] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Accepted: 05/19/2018] [Indexed: 12/13/2022]
Abstract
In all multicellular organisms, immediate host responses to both sterile and infective threat are initiated by very primitive systems now grouped together under the general term 'danger responses'. Danger signals are generated when primitive 'pattern recognition receptors' (PRR) encounter activating 'alarmins'. These molecular species may be of pathogenic infective origin (pathogen-associated molecular patterns) or of sterile endogenous origin (danger-associated molecular patterns). There are many sterile and infective alarmins and there is considerable overlap in their ability to activate PRR, but in all cases the end result is inflammation. It is the overlap between sterile and infective signals acting via a relatively limited number of PRR that generally underlies the great clinical similarity we see between sterile and infective systemic inflammatory responses. Mitochondria (MT) are evolutionarily derived from bacteria, and thus they sit at the crossroads between sterile and infective danger signal pathways. Many of the molecular species in mitochondria are alarmins, and so the release of MT from injured cells results in a wide variety of inflammatory events. This paper discusses the known participation of MT in inflammation and reviews what is known about how the major.
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Abstract
PURPOSE OF REVIEW The purpose of this review is to describe established and emerging mechanisms of gut injury and dysfunction in trauma, describe emerging strategies to improve gut dysfunction, detail the effect of trauma on the gut microbiome, and describe the gut-brain connection in traumatic brain injury. RECENT FINDINGS Newer data suggest intraluminal contents, pancreatic enzymes, and hepatobiliary factors disrupt the intestinal mucosal layer. These mechanisms serve to perpetuate the inflammatory response leading to multiple organ dysfunction syndrome (MODS). To date, therapies to mitigate acute gut dysfunction have included enteral nutrition and immunonutrition; emerging therapies aimed to intestinal mucosal layer disruption, however, include protease inhibitors such as tranexamic acid, parenteral nutrition-supplemented bombesin, and hypothermia. Clinical trials to demonstrate benefit in humans are needed before widespread applications can be recommended. SUMMARY Despite resuscitation, gut dysfunction promotes distant organ injury. In addition, postresuscitation nosocomial and iatrogenic 'hits' exaggerate the immune response, contributing to MODS. This was a provocative concept, suggesting infectious and noninfectious causes of inflammation may trigger, heighten, and perpetuate an inflammatory response culminating in MODS and death. Emerging evidence suggests posttraumatic injury mechanisms, such as intestinal mucosal disruption and shifting of the gut microbiome to a pathobiome. In addition, traumatic brain injury activates the gut-brain axis and increases intestinal permeability.
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40
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Abstract
Microfluidic organ-on-a-chip models of human intestine have been developed and used to study intestinal physiology and pathophysiology. In this article, we review this field and describe how microfluidic Intestine Chips offer new capabilities not possible with conventional culture systems or organoid cultures, including the ability to analyze contributions of individual cellular, chemical, and physical control parameters one-at-a-time; to coculture human intestinal cells with commensal microbiome for extended times; and to create human-relevant disease models. We also discuss potential future applications of human Intestine Chips, including how they might be used for drug development and personalized medicine.
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41
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Does bacterial translocation influence the postoperative infections in splenectomized patients after abdominal trauma? Surgeon 2018; 16:94-100. [DOI: 10.1016/j.surge.2016.09.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2016] [Revised: 09/05/2016] [Accepted: 09/10/2016] [Indexed: 01/14/2023]
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42
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Abstract
Trauma can affect any individual at any location and at any time over a lifespan. The disruption of macrobarriers and microbarriers induces instant activation of innate immunity. The subsequent complex response, designed to limit further damage and induce healing, also represents a major driver of complications and fatal outcome after injury. This Review aims to provide basic concepts about the posttraumatic response and is focused on the interactive events of innate immunity at frequent sites of injury: the endothelium at large, and sites within the lungs, inside and outside the brain and at the gut barrier.
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43
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Evaluation of gut-blood barrier dysfunction in various models of trauma, hemorrhagic shock, and burn injury. J Trauma Acute Care Surg 2017; 83:944-953. [DOI: 10.1097/ta.0000000000001654] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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44
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Fay KT, Ford ML, Coopersmith CM. The intestinal microenvironment in sepsis. Biochim Biophys Acta Mol Basis Dis 2017; 1863:2574-2583. [PMID: 28286161 PMCID: PMC5589488 DOI: 10.1016/j.bbadis.2017.03.005] [Citation(s) in RCA: 116] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2016] [Revised: 02/16/2017] [Accepted: 03/06/2017] [Indexed: 12/17/2022]
Abstract
The gastrointestinal tract has long been hypothesized to function as "the motor" of multiple organ dysfunction syndrome. The gastrointestinal microenvironment is comprised of a single cell layer epithelia, a local immune system, and the microbiome. These three components of the intestine together play a crucial role in maintaining homeostasis during times of health. However, the gastrointestinal microenvironment is perturbed during sepsis, resulting in pathologic changes that drive both local and distant injury. In this review, we seek to characterize the relationship between the epithelium, gastrointestinal lymphocytes, and commensal bacteria during basal and pathologic conditions and how the intestinal microenvironment may be targeted for therapeutic gain in septic patients.
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Affiliation(s)
- Katherine T Fay
- Department of Surgery, Emory University School of Medicine, Atlanta, GA, United States
| | - Mandy L Ford
- Department of Surgery, Emory University School of Medicine, Atlanta, GA, United States; Emory Transplant Center, Emory University School of Medicine, Atlanta, GA, United States
| | - Craig M Coopersmith
- Department of Surgery, Emory University School of Medicine, Atlanta, GA, United States; Emory Critical Care Center, Emory University School of Medicine, Atlanta, GA, United States.
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45
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Down-regulation of toll-like receptor 4 alleviates intestinal ischemia reperfusion injury and acute lung injury in mice. Oncotarget 2017; 8:13678-13689. [PMID: 28099145 PMCID: PMC5355129 DOI: 10.18632/oncotarget.14624] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2016] [Accepted: 01/06/2017] [Indexed: 12/22/2022] Open
Abstract
Intestinal ischemia reperfusion (IR) injury is a critical problem, which can cause intestinal injury locally and acute lung injury (ALI) distally by inflammatory responses and oxidative stress. Toll-like receptor 4 (TLR4) is involved in innate immune and inflammatory responses. This study was to determine whether TLR4 mutant can attenuate intestinal and lung injuries after intestinal IR. Wild type (WT) and TLR4 mutant mice were submitted to intestinal IR by occluding the superior mesenteric artery. Histological assessment of the intestine and the lung were conducted by HE staining. The levels of proinflammatory cytokines, oxidative stress markers, apoptotic index and other mediators were measured. In addition, a 24-hour survival study was performed. Histological assessment showed that intestinal IR caused serious injuries in the intestine and the lung, corroborated by increased proinflammatory cytokines in the circulation. TLR4 mutant suppressed the histological injuries as demonstrated by significantly decreased pathological scores. Consistent with the morphological results, the TLR4 mutant mice exhibited remarkably lowered cytokine expressions in the intestine (TNF-α, IL-6, IL-1β, and NF-κB) and the lung (NO, iNOS, MCP-1, MIP-2, NF-κB, and Caspase-3). ALT and creatinine were also significantly dampened in the liver and kidney, respectively. Furthermore, the survival rate over the course of 24 hours was significantly improved. Collectively, the findings reveal that TLR4 mutant significantly abated the intestinal IR injury and ALI at least in part by alleviating the inflammatory response and oxidative stress.
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46
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The role of NIGMS P50 sponsored team science in our understanding of multiple organ failure. J Trauma Acute Care Surg 2017; 83:520-531. [PMID: 28538636 DOI: 10.1097/ta.0000000000001587] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
The history of the National Institute of General Medical Sciences (NIGMS) Research Centers in Peri-operative Sciences (RCIPS) is the history of clinical, translational, and basic science research into the etiology and treatment of posttraumatic multiple organ failure (MOF). Born out of the activism of trauma and burn surgeons after the Viet Nam War, the P50 trauma research centers have been a nidus of research advances in the field and the training of future academic physician-scientists in the fields of trauma, burns, sepsis, and critical illness. For over 40 years, research conducted under the aegis of this funding program has led to numerous contributions at both the bedside and at the bench. In fact, it has been this requirement for team science with a clinician-scientist working closely with basic scientists from multiple disciplines that has led the RCIPS to its unrivaled success in the field. This review will briefly highlight some of the major accomplishments of the RCIPS program since its inception, how they have both led and evolved as the field moved steadily forward, and how they are responsible for much of our current understanding of the etiology and pathology of MOF. This review is not intended to be all encompassing nor a historical reference. Rather, it serves as recognition to the foresight and support of many past and present individuals at the NIGMS and at academic institutions who have understood the cost of critical illness and MOF to the individual and to society.
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Defining multiple organ failure after major trauma: A comparison of the Denver, Sequential Organ Failure Assessment, and Marshall scoring systems. J Trauma Acute Care Surg 2017; 82:534-541. [PMID: 28030507 DOI: 10.1097/ta.0000000000001328] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
BACKGROUND Postinjury multiple organ failure (MOF) remains a significant cause of morbidity and mortality. A large number of scoring systems have been proposed to define MOF, with no criterion standard. The purpose of this study was to compare three commonly used scores: the Denver Postinjury Multiple Organ Failure Score, the Sequential Organ Failure Assessment (SOFA), and the Marshall Multiple Organ Dysfunction Score, by descriptive analysis of the populations described by each score, and their predictive ability for mortality. METHODS An observational cohort study was performed at a UK trauma center on major trauma patients requiring intensive care unit admission from 2003 to 2011. A novel trauma database was created, merging national audit data with local electronic monitoring systems. Data were collected on demographics, laboratory results, pharmacy, interventions, and hourly physiological monitoring. The primary outcome measure was mortality within 100 days from injury. Sensitivity analyses and receiver operating characteristic curves were used to assess the predictive ability of MOF scores for mortality. RESULTS In total, 491 patients were included in the trauma database. MOF incidence ranged from 22.8% (Denver) to 40.5% (Marshall) to 58.5% (SOFA). MOF definition did not affect timing of onset, but did alter duration and organ failure patterns. Overall mortality was 10.6%, with Denver MOF associated with the greatest increased risk of death (hazard ratio 3.87, 95% confidence interval, 2.24-6.66). No significant difference was observed in area under the receiver operating characteristic curve values between scores. Marked differences were seen in relative predictors, with Denver showing highest specificity (81%) and SOFA highest sensitivity (73%) for mortality. CONCLUSION The choice of MOF scoring system affects incidence, duration, organ dysfunction patterns, and mortality prediction. We would recommend use of the Denver score since it is simplest to calculate, identifies a high-risk group of patients, and has the strongest association with early trauma mortality. LEVEL OF EVIDENCE Epidemiological study, level III.
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48
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Exosomes, not protein or lipids, in mesenteric lymph activate inflammation: Unlocking the mystery of post-shock multiple organ failure. J Trauma Acute Care Surg 2017; 82:42-50. [PMID: 27779585 DOI: 10.1097/ta.0000000000001296] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
BACKGROUND Previous studies have shown that mesenteric lymph (ML) has a crucial role in driving the systemic inflammatory response after trauma/hemorrhagic shock (T/HS). The specific mediators in the ML that contribute to its biological activity remain unclear despite decades of study. Exosomes are extracellular vesicles that are shed into body fluids such as serum and urine that can mediate intercellular communication. We hypothesized that exosomes are present in the ML after trauma/shock and are responsible for the biological activity of ML. METHODS Male rats underwent cannulation of the vessels and mesenteric lymph duct. T/HS was induced by laparotomy and 60 minutes of HS (mean arterial pressure, 35 mmHg), followed by resuscitation. The ML was collected during three distinct time periods (pre-shock, shock, and resuscitation phase) and subsequently separated into exosome and supernatant fractions. Exosomes were characterized by electron microscope, nanoparticle tracking analysis, and immunoblotting. The biological activity of exosomes and supernatant of ML were characterized using a monocyte NF-κB reporter assay and by measuring macrophage intracellular TNF-α production. RESULTS Exosomes were identified in ML by size and expression of the exosome markers CD63 and HSP70. The number of exosomes present in the ML was 2-fold increased during shock and 4-fold decreased in resuscitation phase compared to pre-shock. However, biological activity of exosomes isolated during the resuscitation phase was markedly increased and caused an 8-fold increase in monocyte NF-κB activation compared to supernatant. Macrophage TNF-α production was also increased after exposure to exosomes harvested in the resuscitation phase. The ML supernatant fraction had no effect on TNF-α production during any phase. CONCLUSIONS Our findings show that exosomes, and not the liquid fraction of ML, are the major component triggering inflammatory responses in monocytes and macrophages after experimental T/HS.
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49
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Burcelin R. [Gut microbiota and immune crosstalk in metabolic disease]. Biol Aujourdhui 2017; 211:1-18. [PMID: 28682223 DOI: 10.1051/jbio/2017008] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2017] [Indexed: 05/28/2023]
Abstract
The aim of the review is to discuss about the role played by the defence crosstalk between the gut microbiota and the intestinal immune system, in the development of metabolic disease focusing on obesity and diabetes. Starting from physiological and pathological stand points and based on the latest published data, this review is addressing how the concept of the hologenome theory of evolution can drive the fate of metabolic disease. The notion of "metabolic infection" to explain the "metabolic inflammation" is discussed. This imply comments about the process of bacterial translocation and impaired intestinal immune defense against commensals. Eventually this review sets the soil for personalized medicine. The monthly increase in the number of publications on the gut microbiota to intestinal immune defense and the control of metabolism demonstrate the importance of this field of investigation. The notion of commensal as "self or non-self" has to be reevaluated in the light of the current data. Furthermore, data demonstrate the major role played by short chain fatty acids, secondary bile acids, LPS, peptidoglycans, indole derivatives, and other bacteria-related molecules on the shaping of cells involved in the intestinal protection against commensals is now becoming a central player in the incidence of metabolic diseases. The literature demonstrates that the onset of metabolic diseases and some specific co-morbidities can be explained by a gut microbiota to intestinal immune system crosstalk. Therefore, one should now consider this avenue of investigation as a putative source of biomarkers and therapeutic targets to personalize the treatment of metabolic disease and its co-morbidities. Gut microbiota is considered as a major regulator of metabolic disease. This reconciles the notion of metabolic inflammation and the epidemic development of the disease. In addition to evidence showing that a specific gut microbiota characterizes patients with obesity, type 2 diabetes, and hepatic steatosis, the mechanisms causal to the disease could be related to the translocation of microbiota from the gut to the tissues, which induces inflammation. The mechanisms regulating such a process are based on the crosstalk between the gut microbiota and the host immune system. The hologenome theory of evolution supports this concept and implies that therapeutic strategies aiming to control glycemia should take into account both the gut microbiota and the host immune system. This review discusses the latest evidence regarding the bidirectional impact of the gut microbiota on host immune system crosstalk for the control of metabolic disease, hyperglycemia, and obesity. To avoid redundancies with the literature, we will focus our attention on the intestinal immune system, identifying evidence for the generation of novel therapeutic strategies, which could be based on the control of the translocation of gut bacteria to tissues. Such novel strategies should hamper the role played by gut microbiota dysbiosis on the development of metabolic inflammation. Recent evidence in rodents allows us to conclude that an impaired intestinal immune system characterizes and could be causal in the development of metabolic disease. The fine understanding of the molecular mechanisms should allow for the development of a first line of treatment for metabolic disease and its co-morbidities.
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Affiliation(s)
- Rémy Burcelin
- Institut National de la Santé et de la Recherche Médicale (INSERM), 31024 Toulouse, France - Université Paul Sabatier (UPS), Unité Mixte de Recherche (UMR) 1048, Hôpital Rangueil, 31400 Toulouse, France - Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), 31432 Toulouse Cedex 4, France
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50
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Lorentz CA, Liang Z, Meng M, Chen CW, Yoseph BP, Breed ER, Mittal R, Klingensmith NJ, Farris AB, Burd EM, Koval M, Ford ML, Coopersmith CM. Myosin light chain kinase knockout improves gut barrier function and confers a survival advantage in polymicrobial sepsis. Mol Med 2017; 23:155-165. [PMID: 28598488 DOI: 10.2119/molmed.2016.00256] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Accepted: 05/31/2017] [Indexed: 02/06/2023] Open
Abstract
Sepsis-induced intestinal hyperpermeability is mediated by disruption of the epithelial tight junction, which is closely associated with the peri-junctional actin-myosin ring. Myosin light chain kinase (MLCK) phosphorylates the myosin regulatory light chain, resulting in increased permeability. The purpose of this study was to determine whether genetic deletion of MLCK would alter gut barrier function and survival from sepsis. MLCK-/- and wild type (WT) mice were subjected to cecal ligation and puncture and assayed for both survival and mechanistic studies. Survival was significantly increased in MLCK-/- mice (95% vs. 24%, p<0.0001). Intestinal permeability increased in septic WT mice compared to unmanipulated mice. In contrast, permeability in septic MLCK-/- mice was similar to that seen in unmanipulated animals. Improved gut barrier function in MLCK-/- mice was associated with increases in the tight junction mediators ZO-1 and claudin 15 without alterations in claudin 1, 2, 3, 4, 5, 7, 8, 13, occludin or JAM-A. Other components of intestinal integrity (apoptosis, proliferation and villus length) were unaffected by MLCK deletion as were local peritoneal inflammation and distant lung injury. Systemic IL-10 was decreased greater than 10-fold in MLCK-/- mice; however, survival was similar between septic MLCK-/- mice given exogenous IL-10 or vehicle. These data demonstrate that deletion of MLCK improves survival following sepsis, associated with normalization of intestinal permeability and selected tight junction proteins.
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Affiliation(s)
- C Adam Lorentz
- Department of Urology, Emory University School of Medicine, Atlanta, GA
| | - Zhe Liang
- Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, Atlanta, GA
| | - Mei Meng
- Department of Critical Care Medicine, Shandong Provincial Hospital Affiliated Shandong University, Jinan, China
| | - Ching-Wen Chen
- Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, Atlanta, GA
| | - Benyam P Yoseph
- Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, Atlanta, GA
| | - Elise R Breed
- Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, Atlanta, GA
| | - Rohit Mittal
- Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, Atlanta, GA
| | - Nathan J Klingensmith
- Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, Atlanta, GA
| | - Alton B Farris
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA
| | - Eileen M Burd
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA
| | - Michael Koval
- Department of Internal Medicine and Emory Alcohol and Lung Biology Center, Emory University School of Medicine, Atlanta, GA
| | - Mandy L Ford
- Department of Surgery and Emory Transplant Center, Emory University School of Medicine, Atlanta, GA
| | - Craig M Coopersmith
- Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, Atlanta, GA
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