Intestinal microbiota impact sepsis associated encephalopathy via the vagus nerve

Li, Suyan; Lv, Jian; Li, Jianguo; Zhao, Zhaolong; Guo, Hui; Zhang, Yanni; Cheng, Shuying; Sun, Jianbin; Pan, Hongming; Fan, Shaopeng; Li, Zhongxin

doi:10.1016/j.neulet.2017.10.008

Cited by 56 publications

(43 citation statements)

References 32 publications

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“…Patients with sepsis that is directly influenced by gastrointestinal infection or antibiotic administration [28] may develop disturbances of the gut microbiota. Animal experiments have found that faecal bacteria transplantation can change the gut microbiota of septic mice, suggesting that faecal bacteria transplantation and vagal nerve block are potential therapeutic targets in SAE [29]. The effects of gut microbiota disturbance and the GBA on SAE development deserve further study, especially with respect to upstream and downstream initiation mechanisms, which may provide more ideas to explore the pathogenesis and early diagnosis of SAE.…”

Section: Discussionmentioning

confidence: 99%

A retrospective study of sepsis-associated encephalopathy: epidemiology, clinical features and adverse outcomes

et al. 2020

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Background Sepsis-associated encephalopathy (SAE) is a common complication of sepsis that may result in worse outcomes. This study was designed to determine the epidemiology, clinical features, and risk factors of SAE. Methods This was a retrospective study of all patients with sepsis who were admitted to the Critical Care Medicine Department of Hangzhou First People’s Hospital Affiliated with Zhejiang University School of Medicine from January 2015 to December 2019. Results A total of 291 sepsis patients were screened, and 127 (43.6%) were diagnosed with SAE. There were significant differences in median age, proportion of underlying diseases such as hypertension, Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, gastrointestinal infections, detection rate of Enterococcus, and 28-day mortality between the SAE and non-SAE groups. Both the SOFA score and APACHE II score were independent risk factors for SAE in patients with sepsis. All 127 SAE patients were divided into survival and non-survival groups. The age, SOFA score, and APACHE II score were independently associated with 28-day mortality in SAE patients. Conclusion In the present retrospective study, nearly half of patients with sepsis developed SAE, which was closely related to poor outcomes. Both the SOFA score and APACHE II score were independent risk factors for predicting the occurrence and adverse outcome of SAE.

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Section: Discussionmentioning

confidence: 99%

A retrospective study of sepsis-associated encephalopathy: epidemiology, clinical features and adverse outcomes

et al. 2020

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“…For example, in a mouse model of Streptococcus pneumoniae sepsis, pre-treatment with oral antibiotics prior to sepsis onset was associated with lower levels of lung TNF-α, a pro-inflammatory cytokine [25], whereas others have shown the opposite effect of gut microbiome depletion on TNF-α [21,22,[37][38][39]. Despite differences in specific cytokine expression between studies, the overall effect of alteration of normal gut microbiome structure prior to sepsis onset appears to be a more robust inflammatory response to sepsis [21,22,25,[37][38][39][40][41].…”

Section: Altered Immune Responsementioning

confidence: 99%

The gut microbiome’s role in the development, maintenance, and outcomes of sepsis

et al. 2020

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The gut microbiome regulates a number of homeostatic mechanisms in the healthy host including immune function and gut barrier protection. Loss of normal gut microbial structure and function has been associated with diseases as diverse as Clostridioides difficile infection, asthma, and epilepsy. Recent evidence has also demonstrated a link between the gut microbiome and sepsis. In this review, we focus on three key areas of the interaction between the gut microbiome and sepsis. First, prior to sepsis onset, gut microbiome alteration increases sepsis susceptibility through several mechanisms, including (a) allowing for expansion of pathogenic intestinal bacteria, (b) priming the immune system for a robust pro-inflammatory response, and (c) decreasing production of beneficial microbial products such as short-chain fatty acids. Second, once sepsis is established, gut microbiome disruption worsens and increases susceptibility to end-organ dysfunction. Third, there is limited evidence that microbiome-based therapeutics, including probiotics and selective digestive decontamination, may decrease sepsis risk and improve sepsis outcomes in select patient populations, but concerns about safety have limited uptake. Case reports of a different microbiome-based therapy, fecal microbiota transplantation, have shown correlation with gut microbial structure restoration and decreased inflammatory response, but these results require further validation. While much of the evidence linking the gut microbiome and sepsis has been established in pre-clinical studies, clinical evidence is lacking in many areas. To address this, we outline a potential research agenda for further investigating the interaction between the gut microbiome and sepsis.

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“…The pathogenesis of SAE remains poorly understood. 15 Increasing evidence showed that neuronal dysfunction TIAN ET AL.…”

Section: Lps-induced Sae and Cognitive Dysfunctionmentioning

confidence: 99%

Attractylone attenuates sepsis‐associated encephalopathy and cognitive dysfunction by inhibiting microglial activation and neuroinflammation

Tian

Liu

et al. 2019

J of Cellular Biochemistry

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Multiple studies demonstrated that sepsis is a life‐threatening state of organ dysfunction caused by infection and can induce neuroinflammation and cognitive impairment. The aim of this study was to evaluate the protective effects of attractylone (Atr) on sepsis‐associated encephalopathy (SAE) and cognitive dysfunction. Moreover, we studied the underlying molecular mechanisms. We used an LPS‐induced sepsis mouse model and evaluated the cognitive function with the Morris water maze and open field test. Neuronal damage in the hippocampus was assessed by immunohistochemical analysis. BV2 cells were used to identify the protective mechanism of Atr. The result showed that Atr attenuated LPS‐induced cognitive impairment, neural apoptosis, inflammatory factors, and microglial activation. The in vitro experiment showed that Atr promoted silent information regulator 1 (SIRT1) expression and suppressed NFκB expression. Downregulation of SIRT1 reversed the protective effect of Atr in the LPS condition. Moreover, Atr‐induced SIRT1 expression promoted BV2 from LPS‐induced M1 to M2 phenotype. Taken together, these results indicated that Atr was a potential therapeutic agent for SAE and cognitive dysfunction.

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Intestinal microbiota impact sepsis associated encephalopathy via the vagus nerve

Abstract: FMT can change intestinal microbiota in sepsis patients, and vagus nerve is a key mediator between intestinal microbiota and SAE. These findings suggest that FMT and vagus nerve are potential therapy targets for treating SAE.

Cited by 56 publications

References 32 publications

A retrospective study of sepsis-associated encephalopathy: epidemiology, clinical features and adverse outcomes

A retrospective study of sepsis-associated encephalopathy: epidemiology, clinical features and adverse outcomes

The gut microbiome’s role in the development, maintenance, and outcomes of sepsis

Attractylone attenuates sepsis‐associated encephalopathy and cognitive dysfunction by inhibiting microglial activation and neuroinflammation

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