Gut Microbiota Disruption in Septic Shock Patients: A Pilot Study

Wan, Yong; Wu, Ziqian; Lyu, Shaoyan; Zhao, Lianxing; Du, Zhongjun; Pan, Xinting

doi:10.12659/msm.911768

Cited by 32 publications

(33 citation statements)

References 19 publications

(28 reference statements)

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“… 30 – 32 Furthermore, the higher abundance of Fusobacterium species (OTU48) in sepsis samples was already reported for ICU patients with septic shock. 33 Accordingly, taking into account the association of Bilophila spp. and Fusobacterium spp.…”

Section: Discussionmentioning

confidence: 99%

Gut microbiota profiles in critically ill patients, potential biomarkers and risk variables for sepsis

et al. 2020

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Critically ill patients are physiologically unstable and recent studies indicate that the intestinal microbiota could be involved in the health decline of such patients during ICU stays. This study aims to assess the intestinal microbiota in critically ill patients with and without sepsis and to determine its impact on outcome variables, such as medical complications, ICU stay time, and mortality. A multi-center study was conducted with a total of 250 peri-rectal swabs obtained from 155 patients upon admission and during ICU stays. Intestinal microbiota was assessed by sequencing the V3-V4 hypervariable regions of the 16S rRNA gene. Linear mixed models were used to integrate microbiota data with more than 40 clinical and demographic variables to detect covariates and minimize the effect of confounding factors. We found that the microbiota of ICU patients with sepsis has an increased abundance of microbes tightly associated with inflammation, such as Parabacteroides, Fusobacterium and Bilophila species. Female sex and aging would represent an increased risk for sepsis possibly because of some of their microbiota features. We also evidenced a remarkable loss of microbial diversity, during the ICU stay. Concomitantly, we detected that the abundance of pathogenic species, such as Enterococcus spp., was differentially increased in sepsis patients who died, indicating these species as potential biomarkers for monitoring during ICU stay. We concluded that particular intestinal microbiota signatures could predict sepsis development in ICU patients. We propose potential biomarkers for evaluation in the clinical management of ICU patients.

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Section: Discussionmentioning

confidence: 99%

Gut microbiota profiles in critically ill patients, potential biomarkers and risk variables for sepsis

et al. 2020

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“…Gut microbiome composition with fewer total obligate anaerobes [63] and abundant Enterococcus [17] at sepsis onset have been associated with mortality, whereas other studies have shown that microbiome diversity does not appear to be associated with mortality in sepsis [17,59,61]. In some of these studies, not all patients had sepsis, and sepsis patients were not analyzed as a subset [17,59,61]. Further studies designed to specifically track adverse outcomes in sepsis are needed to characterize the impact of gut microbiome changes, both composition and diversity, on sepsis outcomes.…”

Section: Gut Microbiome and End-organ Damage In Sepsismentioning

confidence: 97%

“…ARDS, acute respiratory distress syndrome; FMT, fecal microbiota transplant; MDRO, multi-drug resistant organism; SCFA, short-chain fatty acid sepsis, including AKI and ARDS, and did not identify an effect on these outcomes [59]. Gut microbiome composition with fewer total obligate anaerobes [63] and abundant Enterococcus [17] at sepsis onset have been associated with mortality, whereas other studies have shown that microbiome diversity does not appear to be associated with mortality in sepsis [17,59,61]. In some of these studies, not all patients had sepsis, and sepsis patients were not analyzed as a subset [17,59,61].…”

Section: Gut Microbiome and End-organ Damage In Sepsismentioning

confidence: 97%

“…Several prospective cohort studies have identified an association between decreased gut microbiome diversity in sepsis and higher relative abundance of potentially pathogenic bacteria including aerobic gram negatives [39,46,56,[59][60][61]. The earliest study to examine microbiome changes in critically ill patients showed that patients with systemic inflammatory response syndrome (SIRS) had lower abundance of obligate anaerobes, and their gut microbiomes were enriched with potential pathogens such as Staphylococcus and Pseudomonas [46].…”

Section: Sepsis Worsens Gut Microbiome Disruptionmentioning

confidence: 99%

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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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“…It is shown that increased abundance of proteobacteria community in the gut might contribute to low-fat/high-sugar diet-induced liver damage and high-fat dietinduced psychiatric disorders in mice [39,40]. Proteobacteria is the dominant phyla in septic patients [41,42]. To determine the causal link between post-septic SD-induced aggravation of systemic in ammation and gut microbiome, pseudo germ-free mice were constructed as recipients receiving fecal microbiota from septic mice with or without SD.…”

Section: Discussionmentioning

confidence: 99%

A key role of gut microbiota-vagus nerve axis and gut microbiota-spleen axis in sleep deprivation-mediated aggravation of systemic inflammation after LPS administration

Zhang

Xie

et al. 2020

Preprint

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Background: Sleep deprivation (SD) is shown to be correlated with exacerbated systemic inflammation after sepsis. However, the underlying mechanisms remain unclear. Methods: In this study, mice were intraperitoneally injected with lipopolysaccharide (LPS) followed by 3 consecutive days of SD. The subdiaphragmatic vagotomy (SDV) was performed 2 weeks before LPS injection. The pseudo germ-free mouse model was created by administering antibiotics for 14 consecutive days, and then fecal microbiota transplant (FMT) was performed by gavaging supernatant from fecal suspension of septic mice with or without SD into pseudo germ-free mice with or without SDV or splenectomy. Splenectomy was performed 14 days prior to antibiotics administration.Results: We found that SD after LPS administration increased the plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), reduced IL-10 plasma leve, increased spleen weight, and promoted pathological injury and IL-6 expression in lung, liver and kidney. Post-septic sleep deprivation had no effects on the diversity of gut microbiota. However, the relative abundance of Proteobacteria and its subgroups were increased in septic mice received SD. Pseudo germ-free mice transplanted with fecal bacteria from septic mice subjected to SD developed splenomegaly, systemic inflammation, organ inflammation and damage as their donors do. Intriguingly, SDV abolished the aggravated effects of SD on splenomegaly and inflammatory organ injury in septic mice received SD or in pseudo germ-free mice transplanted with fecal bacteria from septic mice subjected to SD. Furthermore, Splenectomy also abrogated the increase in IL-6 and TNF-α plasma levels and the decrease in IL-10 plasma level in pseudo germ-free mice transplanted with fecal bacteria from septic mice subjected to SD. Conclusions: Taken together, our results suggest that gut microbiota-vagus nerve axis and gut microbiota-spleen axis could play key roles in modulating systemic inflammation induced by SD after LPS administration.

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Gut Microbiota Disruption in Septic Shock Patients: A Pilot Study

Cited by 32 publications

References 19 publications

Gut microbiota profiles in critically ill patients, potential biomarkers and risk variables for sepsis

Gut microbiota profiles in critically ill patients, potential biomarkers and risk variables for sepsis

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

A key role of gut microbiota-vagus nerve axis and gut microbiota-spleen axis in sleep deprivation-mediated aggravation of systemic inflammation after LPS administration

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