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Host-Microbiome Interactions Mediated by Phenolic Metabolites in Chronically Critically Ill Patients.

ABSTRACT: The community structure and metabolic potential of gut microbiome is not well investigated, especially in chronically critically ill patients with prolonged dependence on support systems after severe brain disorders. Microbial phenolic metabolites can target the brain function by the direct and indirect modulation of inflammation. The aim of this study was to investigate the features of the gut microbiota and profile of certain metabolites in the progression and reversibility of neurological disorders in chronically critically ill patients. Fecal samples were collected in dynamics from such patients (n = 44) and analyzed using 16S rRNA sequencing. Serum microbial and mitochondrial metabolites were measured by GC-MS and compared with the biomarkers and clinical neurological scores. The identified associations between specific bacterial taxa in fecal samples, neurological status and serum levels of metabolites suggest that impacts on specific members of the gut microbiota and their metabolism might be a promising tool for regulating brain function in future.

SUBMITTER: Chernevskaya E

PROVIDER: S-EPMC7924600 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Host-Microbiome Interactions Mediated by Phenolic Metabolites in Chronically Critically Ill Patients.

Chernevskaya Ekaterina E Klimenko Natalia N Pautova Alisa A Buyakova Irina I Tyakht Alexander A Beloborodova Natalia N

Metabolites 20210220 2

The community structure and metabolic potential of gut microbiome is not well investigated, especially in chronically critically ill patients with prolonged dependence on support systems after severe brain disorders. Microbial phenolic metabolites can target the brain function by the direct and indirect modulation of inflammation. The aim of this study was to investigate the features of the gut microbiota and profile of certain metabolites in the progression and reversibility of neurological dis ...[more]

PMID: 33672777

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Project description:Gut microbiome in critically ill patients shows profound dysbiosis. The most vulnerable is the subgroup of chronically critically ill (CCI) patients - those suffering from long-term dependence on support systems in intensive care units. It is important to investigate their microbiome as a potential reservoir of opportunistic taxa causing co-infections and a morbidity factor. We explored dynamics of microbiome composition in the CCI patients by combining "shotgun" metagenomics with chromosome conformation capture (Hi-C). Stool samples were collected at 2 time points from 2 patients with severe brain injury with different outcomes within a 1-2-week interval. The metagenome-assembled genomes (MAGs) were reconstructed based on the Hi-C data using a novel hicSPAdes method (along with the bin3c method for comparison), as well as independently of the Hi-C using MetaBAT2. The resistomes of the samples were derived using a novel assembly graph-based approach. Links of bacteria to antibiotic resistance genes, plasmids and viruses were analyzed using Hi-C-based networks. The gut community structure was enriched in opportunistic microorganisms. The binning using hicSPAdes was superior to the conventional WGS-based binning as well as to the bin3c in terms of the number, completeness and contamination of the reconstructed MAGs. Using Klebsiella pneumoniae as an example, we showed how chromosome conformation capture can aid comparative genomic analysis of clinically important pathogens. Diverse associations of resistome with antimicrobial therapy from the level of assembly graphs to gene content were discovered. Analysis of Hi-C networks suggested multiple "host-plasmid" and "host-phage" links. Hi-C metagenomics is a promising technique for investigating clinical microbiome samples. It provides a community composition profile with increased details on bacterial gene content and mobile genetic elements compared to conventional metagenomics. The ability of Hi-C binning to encompass the MAG's plasmid content facilitates metagenomic evaluation of virulence and drug resistance dynamics in clinically relevant opportunistic pathogens. These findings will help to identify the targets for developing cost-effective and rapid tests for assessing microbiome-related health risks.

Project description:BackgroundProtracted treatment on intensive care unit (ICU) sets the patients at increased risk for the development of chronic critical illness (CCI). Muscular and cardio-respiratory deconditioning are common long-term sequelae, going along with a state of chronic fatigue. At present, findings regarding the frequency, long-term course, and associated factors of self-reported fatigue following ICU treatment of CCI patients are lacking.MethodsCCI patients with the diagnosis of critical illness polyneuropathy/myopathy (CIP/CIM) were assessed at three time points. Four weeks following the discharge from ICU at acute care hospital (t1), eligibility for study participation was asserted. Self-reported fatigue was measured using the Multidimensional Fatigue Inventory (MFI-20) via telephone contact at 3 (t2, n = 113) and 6 months (t3, n = 91) following discharge from ICU at acute care hospital.ResultsAt both 3 and 6 months, nearly every second CCI patient showed clinically relevant fatigue symptoms (t2/t3: n = 53/n = 51, point prevalence rates: 46.9%/45.1%). While total fatigue scores remained stable in the whole sample, female patients showed a decrease from 3 to 6 months. The presence of a coronary heart disease, the perceived fear of dying at acute care ICU, a diagnosis of major depression, and the perceived social support were confirmed as significant correlates of fatigue at 3 months. At 6 months, male gender, the number of medical comorbidities, a diagnosis of major depression, and a prior history of anxiety disorder could be identified. A negative impact of fatigue on the perceived health-related quality of life could be ascertained.ConclusionsNearly every second CCI patient showed fatigue symptoms up to 6 months post-ICU. Patients at risk should be informed about fatigue, and appropriate treatment options should be offered to them.Trial registrationThe present study was registered retrospectively at the German Clinical Trials Register (date of registration: 13th of December 2011; registration number: DRKS00003386). Date of enrolment of the first participant to the present trial: 09th of November 2011.

Project description:Objective: COVID19 is caused by the SARS-CoV-2 virus and has been associated with severe inflammation leading to organ dysfunction and mortality. Our aim was to profile the transcriptome in leukocytes from critically ill ICU patients positive for COVID19 vs. those negative for COVID19 to better understand the COVID19 associated host response. Design: Transcriptome profiling of buffy coat cells via ribonucleic acid sequencing (RNAseq) at the time of admission to the ICU. Setting: Tertiary care ICU and academic laboratory. Subjects: All patients admitted to the ICU suspected of being infected with SARS-CoV-2, using standardized hospital screening methodologies, had blood samples collected at the time of admission to the ICU. Interventions: None. Measurement and Main Results: Age- and sex-matched ICU patients that were either COVID19+ (PCR positive, 2 genes) or COVID19- (PCR negative) were enrolled. Cohorts were well-balanced with the exception that COVID19- patients had significantly higher total white blood cell counts and circulating neutrophils and COVID19+ patients were more likely to suffer bilateral pneumonia compared to COVID19- patients. Further, the mortality rate for this cohort of COVID19+ ICU patients was 29%. Transcriptional analysis revealed that when compared to COVID19- patients, the altered transcriptional responses of leukocytes in critically ill COVID19+ ICU patients appeared to be associated with multiple interrelated outcomes, including but not limited to robust interferon (IFN)-associated transcriptional responses, a marked decrease in the transcriptional activity of genes contributing to protein synthesis and the dysregulated expression of genes that contribute to coagulation, platelet activation, Toll-like receptor activation, neurotrophin signaling, and protein SUMOylation/ubiquitination. Conclusions: COVID19+ patients on day 1 of admission to the ICU display a unique leukocyte transcriptional profile that distinguishes them from COVID19- patients. Identification of this profile provides guidance for future targeted studies exploring novel prognostic/therapeutic aspects of COVID19.

Project description:An increasing amount of evidence has linked critical illness with dysbiotic microbiome signatures in different body sites. The disturbance of the indigenous microbiota structures has been further associated with disease severity and outcome and has been suggested to pose an additional risk for complications in intensive care units (ICUs), including hospital-acquired infections. A better understanding of the microbial dysbiosis in critical illness might thus help to develop strategies for the prevention of such complications. While most of the studies addressing microbiome changes in ICU patients have focused on the gut, the lung, or the oral cavity, little is known about the microbial communities on the skin of ICU patients. Since the skin is the outermost organ and the first immune barrier against pathogens, its microbiome might play an important role in the risk management for critically ill patients. This observational study characterizes the skin microbiome in ICU patients covering five different body sites at the time of admission. Our results show a profound dysbiosis on the skin of critically ill patients, which is characterized by a loss of site specificity and an overrepresentation of gut bacteria on all skin sites when compared to a healthy group. This study opens a new avenue for further investigations on the effect of skin dysbiosis in the ICU setting and points out the need of strategies for the management of dysbiosis in critically ill patients.IMPORTANCEUnbalanced gut microbiota in critically ill patients has been associated with poor outcome and complications during the intensive care unit (ICU) stay. Whether the disturbance of the microbial communities in these patients is extensive for other body sites, such as the skin, is largely unknown. The skin not only is the largest organ of the body but also serves as the first immune barrier against potential pathogens. This study characterized the skin microbiota on five different body sites in ICU patients at the time of admission. The observed disturbance of the bacterial communities might help to develop new strategies in the risk management of critically ill patients.

Dataset Information

Host-Microbiome Interactions Mediated by Phenolic Metabolites in Chronically Critically Ill Patients.

Publications

Host-Microbiome Interactions Mediated by Phenolic Metabolites in Chronically Critically Ill Patients.

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