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

Chernevskaya, Ekaterina; Klimenko, Natalia; Pautova, Alisa; Buyakova, I.V.; Tyakht, Alexander; Белобородова, Н. В.

doi:10.3390/metabo11020122

Cited by 16 publications

(12 citation statements)

References 52 publications

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“…It follows that for a strict statistical analysis -with proper adjustment for the confounding factors -and considering the inherent high dimensionality and multimodality of microbiome data, the required sample size might be very large. In our previous survey of CCI patients' gut microbiome (Chernevskaya et al, 2021), even among 44 patients at the group level we did not observe a prevalent antibiotic therapy pattern -the individual treatments were highly variable. Nevertheless, despite different diagnoses, the chronically critically ill patients convergently acquire the same features of the clinical course, with profound changes in the gut microbiome.…”

Section: Discussionmentioning

confidence: 48%

“…Previously, we characterized the taxonomic composition of microbiome in CCI patients using 16S rRNA sequencing (Chernevskaya et al, 2020). The observed dysbiosis was linked to prognosis and reflected in the altered spectrum of microbially produced phenolic metabolites in blood and stool (Chernevskaya et al, 2021). It suggested the necessity of further investigation of the genetic potential of the microbial species abundant in CCI -including mobile genetic elements -using more powerful approaches like "shotgun" metagenomics.…”

Section: Introductionmentioning

confidence: 99%

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Hi-C Metagenomics in the ICU: Exploring Clinically Relevant Features of Gut Microbiome in Chronically Critically Ill Patients

et al. 2022

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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.

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Section: Discussionmentioning

confidence: 48%

Section: Introductionmentioning

confidence: 99%

Hi-C Metagenomics in the ICU: Exploring Clinically Relevant Features of Gut Microbiome in Chronically Critically Ill Patients

et al. 2022

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“…The interrelation of factors influencing the development of a CCI as a result of long-term violation of the functions of the brain and the gut microbiota has been studied [15]. The results confirm the association of taxonomic composition and profile of certain aromatic metabolites of the gut microbiota with the progression or reversibility of neurological disorders in CCI patients.…”

Section: Microbiome and Inflammatory Events After Strokementioning

confidence: 56%

“…The Glasgow Coma Scale (GCS), the National Institutes of Health Stroke Scale (NIHSS), the Rivermead Mobility Index Scale, and the Rankin scale were used to assess neurological status over time, while the monitoring of serum PhCAs levels was performed by gas chromatography-mass spectrometry (GC-MS). Results showed that the positive dynamics of neurological status in patients with brain damage was associated with serum level of phenylpropionic acid (PhPA) [15]. Based on studies that have established that PhPA is the end product of tyrosine metabolism by Clostridia sporogenes [16,17], we believe that special attention should be paid to further confirmation of the involvement of C. sporogenes and studying the pathophysiological role of its metabolites in the process of neurorehabilitation.…”

Section: Phenolic Metabolites Of Tyrosinementioning

confidence: 99%

“Dialogue” between the Human Microbiome and the Brain

Белобородова¹,

Grechko²

2021

Human Microbiome

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In conditions of severe gut dysbiosis, there is a risk of developing diseases of the host organism in general and of the brain in particular, as evidenced by a growing number of studies. This chapter focuses on several groups of low-molecular-weight compounds that originate primarily from the gut microbiota. It discusses the results of experimental and clinical studies on the effect of microbial metabolites (such as short-chain fatty acids, phenolic metabolites of tyrosine, indolic metabolites of tryptophan, trimethylamines) on the brain. Several studies have proven that the microbial metabolite profiles in the gut and serum are interlinked and reflect a disruption of the gut microbial community. Using 16S ribosomal RNA gene sequencing, it was found that the gut microbiota of patients with positive or negative dynamics of neurological status differ taxonomically. The chapter also presents data obtained from animal germ-free (GF) models. Many researchers would like to consider the gut microbiota as a new therapeutic target, including for the treatment of brain diseases, stroke prevention, reduction of neuroinflammation, and more successful neurorehabilitation of patients.

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“…Several studies of gut microbiota dynamics in ICU patients using 16S rRNA gene sequencing indicate a rapid disruption of gut microbiota during ICU stay, and this is associated with a loss of diversity and overgrowth of potentially pathogenic microorgan-isms [16][17][18][19]. The microbial disbalance in the gut may have a clinical relevance and can lead to inflammation and infection [20], also playing a potential role in neurological deficits [21].…”

Section: Introductionmentioning

confidence: 99%

Gut Microbiota as Early Predictor of Infectious Complications before Cardiac Surgery: A Prospective Pilot Study

Chernevskaya

Zuev

Odintsova³

et al. 2021

JPM

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Cardiac surgery remains a field of medicine with a high percentage of postoperative complications, including infectious ones. Modern data indicate a close relationship of infectious disorders with pathological changes in the composition of the gut microbiome; however, the extent of such changes in cardiac surgery patients is not fully clarified. In this prospective, observational, single center, pilot study, 72 patients were included, 12 among them with the infectious complications. We analyzed the features of the fecal microbiota before and in the early postoperative period, as one of the markers for predicting the occurrence of bacterial infection. We also discovered the significant change in microbial composition in the group of patients with infectious complications compared to the non-infectious group before and after cardiac surgery, despite the intra-individual variation in composition of gut microbiome. Our study demonstrated that the group of patients that had a bacterial infection in the early postoperative period already had an altered microbial composition even before the surgery. Further studies will evaluate the clinical significance of the identified proportions of individual taxa of the intestinal microbiota and consider the microbiota as a novel target for reducing the risk of infectious complications.

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

Cited by 16 publications

References 52 publications

Hi-C Metagenomics in the ICU: Exploring Clinically Relevant Features of Gut Microbiome in Chronically Critically Ill Patients

Hi-C Metagenomics in the ICU: Exploring Clinically Relevant Features of Gut Microbiome in Chronically Critically Ill Patients

“Dialogue” between the Human Microbiome and the Brain

Gut Microbiota as Early Predictor of Infectious Complications before Cardiac Surgery: A Prospective Pilot Study

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