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

Meng, Mei; Klingensmith, Nathan J.; Coopersmith, Craig M.

doi:10.1097/mcc.0000000000000386

Cited by 131 publications

(84 citation statements)

References 51 publications

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“…The intestine is an important contributor to MODS, and intestinal I/R injury compromises the whole organism and survival. 33 Unlike other organs, the liver has a dual blood supply system involving the hepatic artery and portal vein that mainly collects blood from the spleen, stomach, intestine, and mesentery. Therefore, the gut-liver axis is crucial for maintaining the normal morphology and function of these two organs.…”

Section: Discussionmentioning

confidence: 99%

HMGB1‐associated necroptosis and Kupffer cells M1 polarization underlies remote liver injury induced by intestinal ischemia/reperfusion in rats

Wen

Ling

et al. 2020

FASEB j.

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Reperfusion of the ischemic intestine often leads to drive distant organ injury, especially injuries associated with hepatocellular dysfunction. The precise molecular mechanisms and effective multiple organ protection strategies remain to be developed. In the current study, significant remote liver dysfunction was found after 6 hours of reperfusion according to increased histopathological scores, serum lactate dehydrogenase (LDH), alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels, as well as enhanced bacterial translocation in a rat intestinal ischemia/reperfusion (I/R) injury model. Moreover, receptor‐interacting protein kinase 1/3 (RIP1/3) and phosphorylated‐MLKL expressions in tissue were greatly elevated, indicating that necroptosis occurred and resulted in acute remote liver function impairment. Inhibiting the necroptotic pathway attenuated HMGB1 cytoplasm translocation and tissue damage. Meanwhile, macrophage‐depletion study demonstrated that Kupffer cells (KCs) are responsible for liver damage. Blocking HMGB1 partially restored the liver function via suppressed hepatocyte necroptosis, tissue inflammation, hepatic KCs, and circulating macrophages M1 polarization. What’s more, HMGB1 neutralization further protects against intestinal I/R‐associated liver damage in microbiota‐depleted rats. Therefore, intestinal I/R is likely associated with acute liver damage due to hepatocyte necroptosis, and which could be ameliorated by Nec‐1 administration and HMGB1 inhibition with the neutralizing antibody and inhibitor. Necroptosis inhibition and HMGB1 neutralization/inhibition, may emerge as effective pharmacological therapies to minimize intestinal I/R‐induced acute remote organ dysfunction.

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Section: Discussionmentioning

confidence: 99%

HMGB1‐associated necroptosis and Kupffer cells M1 polarization underlies remote liver injury induced by intestinal ischemia/reperfusion in rats

Wen

Ling

et al. 2020

FASEB j.

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“…Whereas the most common microbe makes up 25% of the microbiome in healthy patients, a massive diversity crash causes results in the most common microbe making up 95% of the microbiome in ICU patients [215]. These changes appear to result from both the underlying disorder (sepsis) and its treatment (antibiotics), which by definition alter the microbiome [216][217][218][219][220][221][222]. Further, microbes alter their virulence in response to both the internal host environment (availability of phosphate) and treatments in critically ill patients (opiates) [223][224][225].…”

Section: Basic/translational Science What Mechanisms Underlie Sepsis-mentioning

confidence: 99%

Surviving sepsis campaign: research priorities for sepsis and septic shock

et al. 2018

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Objective: To identify research priorities in the management, epidemiology, outcome and underlying causes of sepsis and septic shock.Design: A consensus committee of 16 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine was convened at the annual meetings of both societies. Subgroups had teleconference and electronic-based discussion. The entire committee iteratively developed the entire document and recommendations.Methods: Each committee member independently gave their top five priorities for sepsis research. A total of 88 suggestions (ESM 1 -supplemental table 1) were grouped into categories by the committee co-chairs, leading to the formation of seven subgroups: infection, fluids and vasoactive agents, adjunctive therapy, administration/epidemiology, scoring/identification, post-intensive care unit, and basic/translational science. Each subgroup had teleconferences to go over each priority followed by formal voting within each subgroup. The entire committee also voted on top priorities across all subgroups except for basic/translational science. Results:The Surviving Sepsis Research Committee provides 26 priorities for sepsis and septic shock. Of these, the top six clinical priorities were identified and include the following questions: (1) can targeted/personalized/precision medicine approaches determine which therapies will work for which patients at which times?; (2) what are ideal endpoints for volume resuscitation and how should volume resuscitation be titrated?; (3) should rapid diagnostic tests be implemented in clinical practice?; (4) should empiric antibiotic combination therapy be used in sepsis or septic shock?; (5) what are the predictors of sepsis long-term morbidity and mortality?; and (6) what information identifies organ dysfunction?Conclusions: While the Surviving Sepsis Campaign guidelines give multiple recommendations on the treatment of sepsis, significant knowledge gaps remain, both in bedside issues directly applicable to clinicians, as well as understanding the fundamental mechanisms underlying the development and progression of sepsis. The priorities identified represent a roadmap for research in sepsis and septic shock.

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“…At present, the intestine is viewed as playing an important role in the processes of systemic inflammation, sepsis, multiple organ failure, and progression of AP [53][54][55][56]. Damage to the intestinal barrier in AP is caused by disturbances in microcirculation resulted from the increasing intestinal pressure, shock, and the occurrence of microthrombosis [57].…”

Section: Authorsmentioning

confidence: 99%

Аntibacterial and Antifungal Therapy for Patients with Acute Pancreatitis at High Risk of Pancreatogenic Sepsis (Review)

Firsova¹,

Паршиков

Кукош

et al. 2020

Sovrem Tehnol Med

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Controlling infection is crucial in treating patients with acute pancreatitis (AP). The infectious process in AP often predisposes to subsequent sepsis by damaging not only the pancreas, but retroperitoneal tissues as well. Among other AP-associated factors, are the rapidly developing immune imbalance, the poor penetration of antimicrobial agents into necrotic tissue, and the impossibility of a single surgical debridement. Antibacterial and antifungal therapy for patients with infected necrosis and AP-associated extra-pancreatic infections remains a complex and largely unresolved problem, partially due to the high occurrence of multiresistant pathogens. The preventive use of antimicrobial agents has been discussed in the literature; however, the lack of consistent results makes it difficult to develop a unified strategy and clinical guidelines on this specific issue. Recent meta-analyses provide no conclusive evidence that antibacterial prophylaxis reduces the infection rate, mortality, or the need for surgical treatment in patients with necrotizing pancreatitis. We found only two studies indicating the benefits of using carbapenems for prophylactic purposes and one meta-analysis indicating a reduction in mortality under antibiotic treatment started no later than 72 h after the onset of the attack. Selective bowel decontamination is considered as one of the preventive anti-infection measures, although the available data may not be fully reliable. The main indications for antibacterial therapy in patients with AP are confirmed infected necrosis or extra-pancreatic infection, as well as clinical symptoms of suspected infection. Intra-arterial administration or local treatment with antibiotics can increase the efficacy of antibacterial therapy. No randomized studies on antifungal prophylaxis in AP are available; some reports though recommend using such therapy among patients at high risk of invasive candidiasis.

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

Cited by 131 publications

References 51 publications

HMGB1‐associated necroptosis and Kupffer cells M1 polarization underlies remote liver injury induced by intestinal ischemia/reperfusion in rats

HMGB1‐associated necroptosis and Kupffer cells M1 polarization underlies remote liver injury induced by intestinal ischemia/reperfusion in rats

Surviving sepsis campaign: research priorities for sepsis and septic shock

Аntibacterial and Antifungal Therapy for Patients with Acute Pancreatitis at High Risk of Pancreatogenic Sepsis (Review)

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