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Classification of the Gut Microbiota of Patients in Intensive Care Units During Development of Sepsis and Septic Shock.

ABSTRACT: The gut microbiota of intensive care unit (ICU) patients displays extreme dysbiosis associated with increased susceptibility to organ failure, sepsis, and septic shock. However, such dysbiosis is difficult to characterize owing to the high dimensional complexity of the gut microbiota. We tested whether the concept of enterotype can be applied to the gut microbiota of ICU patients to describe the dysbiosis. We collected 131 fecal samples from 64 ICU patients diagnosed with sepsis or septic shock and performed 16S rRNA gene sequencing to dissect their gut microbiota compositions. During the development of sepsis or septic shock and during various medical treatments, the ICU patients always exhibited two dysbiotic microbiota patterns, or ICU-enterotypes, which could not be explained by host properties such as age, sex, and body mass index, or external stressors such as infection site and antibiotic use. ICU-enterotype I (ICU E1) comprised predominantly Bacteroides and an unclassified genus of Enterobacteriaceae, while ICU-enterotype II (ICU E2) comprised predominantly Enterococcus. Among more critically ill patients with Acute Physiology and Chronic Health Evaluation II (APACHE II) scores > 18, septic shock was more likely to occur with ICU E1 (P = 0.041). Additionally, ICU E1 was correlated with high serum lactate levels (P = 0.007). Therefore, different patterns of dysbiosis were correlated with different clinical outcomes, suggesting that ICU-enterotypes should be diagnosed as independent clinical indices. Thus, the microbial-based human index classifier we propose is precise and effective for timely monitoring of ICU-enterotypes of individual patients. This work is a first step toward precision medicine for septic patients based on their gut microbiota profiles.

SUBMITTER: Liu W

PROVIDER: S-EPMC8377022 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAccurate and early identification of infection sites might help to drive crucial decisions regarding the treatment of sepsis. We aimed to determine the clinical and etiological features of infection according to sites among patients with severe sepsis in Japan.MethodsThis secondary analysis of a multicenter, prospective cohort study included 59 intensive care units (ICU) and proceeded between January 2016 and March 2017. The study cohort comprised 1184 adults (≥ 16 years) who were admitted to an ICU with severe sepsis and septic shock diagnosed according to the sepsis-2 criteria. Sites of infection diagnosed by physicians in charge at the time of arrival comprised the lung, abdomen, urinary tract, soft tissue, bloodstream, central nervous system (CNS), and undifferentiated infections. The primary outcome was in-hospital mortality.ResultsThe most common sites of infection were the lungs (31.0%), followed by intra-abdominal sites (26.3%), the urinary tract (18.4%), and soft tissue (10.9%). The characteristics of the patients with severe sepsis across seven major suspected infection sites were heterogeneous. Septic shock was more frequent among patients with intra-abdominal (72.2%) and urinary tract (70.2%) infections than other sites. The in-hospital mortality rate due to severe sepsis and septic shock of a pooled sample was 23.4% (range, 11.9% [urinary tract infection] to 47.6% [CNS infection]). After adjusting for clinical background, sepsis severity, and stratification according to the presence or absence of shock, variations in hospital mortality across seven major sites of infection remained essentially unchanged from those for crude in-hospital mortality; adjusted in-hospital mortality rates ranged from 7.7% (95%CI, - 0.3 to 15.8) for urinary tract infection without shock to 58.3% (95%CI, 21.0-95.7) for CNS infection with shock in a generalized estimating equation model. Intra-abdominal and urinary tract infections were statistically associated with less in-hospital mortality than pneumonia. Infections of the CNS were statistically associated with higher in-hospital mortality rates than pneumonia in a logistic regression model, but not in the generalized estimating equation model.ConclusionsIn-hospital mortality and clinical features of patients with severe sepsis and septic shock were heterogeneous according to sites of infection.

Project description:Background: The gut is thought to play an important role in the pathogenesis of sepsis. Changes in the gut microbiota are closely related to the occurrence and development of human diseases, but few studies have focused on taxonomic composition of gut microbiota in septic patients. Knowledge of changes in the gut microbiota is a key issue in intensive care. Clinicians must understand how an altered gut microbiota affects the susceptibility and prognosis of septic patients. Measurements and Main Results: In the single-center case control study, 20 septic patients and 20 healthy children were recruited. The taxonomic composition of gut microbiota was determined via 16S rRNA gene sequencing. Gut microbiota diversity in children with sepsis was significantly reduced compared with that in healthy children. The taxonomic composition of gut microbiota can effectively distinguish children with sepsis from healthy children. Thirteen taxa of gut microbiota were significantly increased in the guts of children with sepsis compared with those of healthy children. The increased abundances of Enterococcaceae, Enterococcus, and Enterococcus durans in gut of septic patients were significantly positively correlated with blood inflammation indicators CRP and WBC. The abundances of seven bacteria were significantly decreased in the guts of septic children compared with those of healthy children. The decreased abundance of Bifidobacteriales in gut of septic patients is significantly negatively correlated with blood inflammation index WBC. A machine-learning classifier was built for distinguishing sepsis and achieved the AUC value of 81.25%. It shows that the composition of gut microbiota has certain potential for diagnosis of sepsis. Conclusions: Gut microbiota alterations in septic patients exhibit proliferation of opportunistic pathogenic bacteria, the massive reduction of the commensal flora, and the significant decrease in the diversity of the gut microbiota. Dysbiosis may also account for some changes in the inflammation indexes.

Project description:Procalcitonin (PCT) algorithms for antibiotic treatment decisions have been studied in adult patients from primary care, emergency department, and intensive care unit (ICU) settings, suggesting that procalcitonin-guided therapy may reduce antibiotic exposure without increasing the mortality rate. However, information on the efficacy and safety of this approach in the most vulnerable population of critically ill patients with severe sepsis and septic shock is missing.Two reviewers independently performed a systematic search in PubMed, Embase, ISI Web of Knowledge, BioMed Central, ScienceDirect, Cochrane Central Register of Controlled Trials, http://www.ClinicalTrials.gov and http://www.ISRCTN.org. Eligible studies had to be randomized controlled clinical trials or cohort studies which compare procalcitonin-guided therapy with standard care in severe sepsis patients and report at least one of the following outcomes: hospital mortality, 28-day mortality, duration of antimicrobial therapy, length of stay in the intensive care unit or length of hospital stay. Disagreements about inclusion of studies and judgment of bias were solved by consensus.Finally seven studies comprising a total of 1,075 patients with severe sepsis or septic shock were included in the meta-analysis. Both hospital mortality (RR [relative risk]: 0.91, 95%CI [confidence interval]: 0.61; 1.36) and 28-day mortality (RR: 1.02, 95%CI: 0.85; 1.23) were not different between procalcitonin-guided therapy and standard treatment groups. Duration of antimicrobial therapy was significantly reduced in favor of procalcitonin-guided therapy (HR [hazard ratio]: 1.27, 95%CI: 1.01; 1.53). Combined estimates of the length of stay in the ICU and in hospital did not differ between groups.Procalcitonin-guided therapy is a helpful approach to guide antibiotic therapy and surgical interventions without a beneficial effect on mortality. The major benefit of PCT-guided therapy consists of a shorter duration of antibiotic treatment compared to standard care. Trials are needed to investigate the effect of PCT-guided therapy on mortality, length of ICU and in-hospital stay in severe sepsis patients.

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Classification of the Gut Microbiota of Patients in Intensive Care Units During Development of Sepsis and Septic Shock.

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