The liver-gut-axis: initiator and responder to sepsis

Bauer, Michael

doi:10.1097/mcc.0000000000000921

Cited by 17 publications

(6 citation statements)

References 45 publications

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“…Endotoxins and antigens are transported from the gut into the circulation. [20][21][22] Gut-origin sepsis is a process in which bacteria and bacteria-associated products incite a systemic response. These systemic responses are responsible for other clinical manifestations in critically ill patients with syndromes, such as acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS).…”

Section: Bt In Sepsismentioning

confidence: 99%

The role of bacterial translocation in sepsis: a new target for therapy

Potruch

Schwartz

Ilan

2022

Therap Adv Gastroenterol

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Sepsis is a leading cause of death in critically ill patients, primarily due to multiple organ failures. It is associated with a systemic inflammatory response that plays a role in the pathogenesis of the disease. Intestinal barrier dysfunction and bacterial translocation (BT) play pivotal roles in the pathogenesis of sepsis and associated organ failure. In this review, we describe recent advances in understanding the mechanisms by which the gut microbiome and BT contribute to the pathogenesis of sepsis. We also discuss several potential treatment modalities that target the microbiome as therapeutic tools for patients with sepsis.

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Section: Bt In Sepsismentioning

confidence: 99%

The role of bacterial translocation in sepsis: a new target for therapy

Potruch

Schwartz

Ilan

2022

Therap Adv Gastroenterol

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“…Indeed, circulating bile acids are better predictors of sepsis-related mortality than liver function parameters, such as bilirubin [ 10 , 43 ]. Therefore, several authors speculated that bile acids play an active role in the pathogenesis of sepsis [ 10 , 29 , 45 ]. Moreover, studies have shown that HMG-CoA reductase inhibitors (drugs that significantly inhibit cholesterol and, subsequently, bile acid synthesis) reduce mortality in sepsis and infection-related ARDS [ 46 – 48 ].…”

Section: Discussionmentioning

confidence: 99%

Immunosuppressive effects of circulating bile acids in human endotoxemia and septic shock: patients with liver failure are at risk

Leonhardt,

Dorresteijn,

Neugebauer

et al. 2023

Crit Care

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Background Sepsis-induced immunosuppression is a frequent cause of opportunistic infections and death in critically ill patients. A better understanding of the underlying mechanisms is needed to develop targeted therapies. Circulating bile acids with immunosuppressive effects were recently identified in critically ill patients. These bile acids activate the monocyte G-protein coupled receptor TGR5, thereby inducing profound innate immune dysfunction. Whether these mechanisms contribute to immunosuppression and disease severity in sepsis is unknown. The aim of this study was to determine if immunosuppressive bile acids are present in endotoxemia and septic shock and, if so, which patients are particularly at risk. Methods To induce experimental endotoxemia in humans, ten healthy volunteers received 2 ng/kg E. coli lipopolysaccharide (LPS). Circulating bile acids were profiled before and after LPS administration. Furthermore, 48 patients with early (shock onset within < 24 h) and severe septic shock (norepinephrine dose > 0.4 μg/kg/min) and 48 healthy age- and sex-matched controls were analyzed for circulating bile acids. To screen for immunosuppressive effects of circulating bile acids, the capability to induce TGR5 activation was computed for each individual bile acid profile by a recently published formula. Results Although experimental endotoxemia as well as septic shock led to significant increases in total bile acids compared to controls, this increase was mild in most cases. By contrast, there was a marked and significant increase in circulating bile acids in septic shock patients with severe liver failure compared to healthy controls (61.8 µmol/L vs. 2.8 µmol/L, p = 0.0016). Circulating bile acids in these patients were capable to induce immunosuppression, as indicated by a significant increase in TGR5 activation by circulating bile acids (20.4% in severe liver failure vs. 2.8% in healthy controls, p = 0.0139). Conclusions Circulating bile acids capable of inducing immunosuppression are present in septic shock patients with severe liver failure. Future studies should examine whether modulation of bile acid metabolism can improve the clinical course and outcome of sepsis in these patients. Graphical abstract

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“…This causes frequent transitory bacteremia and could trigger VAP. Impaired lung bacterial clearance, secondary to innate immune deficiency described in cirrhosis, could also be responsible for bacterial proliferation and subsequent VAP [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Are Cirrhotic Patients Receiving Invasive Mechanical Ventilation at Risk of Abundant Microaspiration

Lévy¹,

Gaudet

Jaillette³

et al. 2022

JCM

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Previous studies have identified cirrhosis as a risk factor for ventilator-associated pneumonia (VAP). The aim of our study was to determine the relationship between cirrhosis and abundant gastric-content microaspiration in intubated critically ill patients. We performed a matched cohort study using data from three randomized controlled trials on abundant microaspiration in patients under mechanical ventilation. Each cirrhotic patient was matched with three to four controls for gender, age ± 5 years and simplified acute physiology score II (SAPS II) ± 5 points. Abundant microaspiration was defined by significant levels of pepsin and alpha-amylase in >30% of tracheal aspirates. All tracheal aspirates were collected for the first 48 h of the study period. The percentage of patients with abundant gastric-content microaspiration was the primary outcome. The abundant microaspiration of oropharyngeal secretions, VAP incidence, the duration of mechanical ventilation, length of intensive care unit (ICU) stay and mortality were the secondary outcomes. A. total of 39 cirrhotic patients were matched to 138 controls. The percentage of patients with abundant gastric-content microaspiration did not differ between the two groups (relative risk: 0.91 (95% CI: 0.75 to 1.10)). There was no significant difference between the two groups in terms of the abundant microaspiration of oropharyngeal secretions, VAP, the duration of mechanical ventilation, the length of ICU stay and mortality. Our results suggest that cirrhosis is not associated with abundant gastric-content microaspiration.

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The liver-gut-axis: initiator and responder to sepsis

Cited by 17 publications

References 45 publications

The role of bacterial translocation in sepsis: a new target for therapy

The role of bacterial translocation in sepsis: a new target for therapy

Immunosuppressive effects of circulating bile acids in human endotoxemia and septic shock: patients with liver failure are at risk

Are Cirrhotic Patients Receiving Invasive Mechanical Ventilation at Risk of Abundant Microaspiration

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