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Critically ill patients demonstrate large interpersonal variation in intestinal microbiota dysregulation: a pilot study.

ABSTRACT: The intestinal microbiota has emerged as a virtual organ with essential functions in human physiology. Antibiotic-induced disruption of the microbiota in critically ill patients may have a negative influence on key energy resources and immunity. We set out to characterize the fecal microbiota composition in critically ill patients both with and without sepsis and to explore the use of microbiota-derived markers for clinical outcome measurements in this setting.In this prospective observational cohort study we analyzed the fecal microbiota of 34 patients admitted to the intensive care unit. Fifteen healthy subjects served as controls. The fecal microbiota was phylogenetically characterized by 16S rRNA gene sequencing, and associations with clinical outcome parameters were evaluated.A marked shift in fecal bacterial composition was seen in all septic and non-septic critically ill patients compared with controls, with extreme interindividual differences. In 13 of the 34 patients, a single bacterial genus made up >50% of the gut microbiota; in 4 patients this was even >75%. A significant decrease in bacterial diversity was observed in half of the patients. No associations were found between microbiota diversity, Firmicutes/Bacteroidetes ratio, or Gram-positive/Gram-negative ratio and outcome measurements such as complications and survival.We observed highly heterogeneous patterns of intestinal microbiota in both septic and non-septic critically ill patients. Nevertheless, some general patterns were observed, including disappearance of bacterial genera with important functions in host metabolism. More detailed knowledge of the short- and long-term health consequences of these major shifts in intestinal bacterial communities is needed.

SUBMITTER: Lankelma JM

PROVIDER: S-EPMC5203863 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Critically ill patients demonstrate large interpersonal variation in intestinal microbiota dysregulation: a pilot study.

Lankelma Jacqueline M JM van Vught Lonneke A LA Belzer Clara C Schultz Marcus J MJ van der Poll Tom T de Vos Willem M WM Wiersinga W Joost WJ

Intensive care medicine 20161111 1

<h4>Purpose</h4>The intestinal microbiota has emerged as a virtual organ with essential functions in human physiology. Antibiotic-induced disruption of the microbiota in critically ill patients may have a negative influence on key energy resources and immunity. We set out to characterize the fecal microbiota composition in critically ill patients both with and without sepsis and to explore the use of microbiota-derived markers for clinical outcome measurements in this setting.<h4>Methods</h4>In ...[more]

PMID: 27837233

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Project description:Circadian disruption is common in critically ill patients admitted to the intensive care unit (ICU). Understanding and treating circadian disruption in critical illness has significant potential to improve critical illness outcomes through improved cognitive, immune, cardiovascular, and metabolic function. Measurement of circadian alignment (i.e., circadian phase) can be resource-intensive as it requires frequent blood or urine sampling over 24 or more hours. Less cumbersome methods of assessing circadian alignment would advance investigations in this field. Thus, the objective of this study is to examine the feasibility of using continuous telemetry to assess diurnal variation in heart rate (HR) among medical ICU patients as a proxy for circadian alignment. In exploratory analyses, we tested for associations between misalignment of diurnal variation in HR and death during hospital admission. This was a prospective observational cohort study embedded within a prospective medical ICU biorepository. HR data were continuously collected (every 5 s) via telemetry systems for the duration of the medical ICU admission; the first 24 h of this data was analyzed. Patients were extensively characterized via medical record chart abstraction and patient interviews. Of the 56 patients with complete HR data, 48 (86%) had a detectable diurnal variation. Of these patients with diurnal variation, 39 (81%) were characterized as having the nadir of their HR outside of the normal range of 02:00-06:00 ("misalignment"). Interestingly, no deaths occurred in the patients with normally aligned diurnal variation; in contrast, there were seven deaths (out of 39 patients) in patients who had misaligned diurnal variation in HR. In an exploratory analysis, we found that the odds ratio of death for misaligned vs. aligned patients was increased at 4.38; however, this difference was not statistically significant (95% confidence interval 0.20-97.63). We conclude that diurnal variation in HR can be detected via continuous telemetric monitoring of critically ill patients. A majority of these patients with diurnal variation exhibited misalignment in their first 24 h of medical ICU admission. Exploratory analyses suggest possible associations between misalignment and death.

Project description:Background: Systemic inflammation is a whole body reaction that can have an infection-positive (i.e. sepsis) or infection-negative origin. It is important to distinguish between septic and non-septic presentations early and reliably, because this has significant therapeutic implications for critically ill patients. We hypothesized that a molecular classifier based on a small number of RNAs expressed in peripheral blood could be discovered that would: 1) determine which patients with systemic inflammation had sepsis; 2) be robust across independent patient cohorts; 3) be insensitive to disease severity; and 4) provide diagnostic utility. The overall goal of this study was to identify and validate such a molecular classifier. Methods and Findings: We conducted an observational, non-interventional study of adult patients recruited from tertiary intensive care units (ICU). Biomarker discovery was conducted with an Australian cohort (n = 105) consisting of sepsis patients and post -surgical patients with infection-negative systemic inflammation. Using this cohort, a four-gene classifier consisting of a combination of CEACAM4, LAMP1, PLA2G7 and PLAC8 RNA biomarkers was identified. This classifier, designated SeptiCyteÂ® Lab, was externally validated using RT-qPCR and receiver operating characteristic (ROC) curve analysis in five cohorts (n = 345) from the Netherlands. Cohort 1 (n=59) consisted of unambiguous septic cases and infection-negative systemic inflammation controls; SeptiCyteÂ® Lab gave an area under curve (AUC) of 0.96 (95% CI: 0.91-1.00). ROC analysis of a more heterogeneous group of patients (Cohorts 2-5; 249 patients after excluding 37 patients with infection likelihood possible) gave an AUC of 0.89 (95% CI: 0.85-0.93). Disease severity, as measured by Sequential Organ Failure Assessment (SOFA) score or the Acute Physiology and Chronic Health Evaluation (APACHE) IV score, was not a significant confounding variable. The diagnostic utility o f SeptiCyteÂ® Lab was evaluated by comparison to various clinical and laboratory parameters that would be available to a clinician within 24 hours of ICU admission. SeptiCyteÂ® Lab was significantly better at differentiating sepsis from infection-negative systemic inflammation than all tested parameters, both singly and in various logistic combinations. SeptiCyteÂ® Lab more than halved the diagnostic error rate compared to PCT in all tested cohorts or cohort combinations. Conclusions: SeptiCyteÂ® Lab is a rapid molecular assay that may be clinically useful in the management of ICU patients with systemic inflammation. SIRS and Sepsis ICU patients, admission samples Retrospective, mutli-site sutdy using retrospective physician adjudication as a comparator

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Critically ill patients demonstrate large interpersonal variation in intestinal microbiota dysregulation: a pilot study.

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Critically ill patients demonstrate large interpersonal variation in intestinal microbiota dysregulation: a pilot study.

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