Phenylcarboxylic Acids in The Assessment of The Severity of Patient Condition and The Efficiency of Intensive Treatment in Critical Care Medicine

Мороз, В. В.; Белобородова, Н. В.; Осипов, А.А.; Власенко, А. В.; Бедова, А. Ю.; Pautova, Alisa

doi:10.15360/1813-9779-2016-4-37-48

Cited by 19 publications

(17 citation statements)

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“…At the same time, the summary levels of microbial metabolites in the serum samples were higher for the ACI patients. Earlier, we have shown that the sum of three AMM (p-HPhAA, p-HPhLA, PhLA) reflects the severity of disease in patients admitted to ICU as good as conventional scales APACHE II and SOFA [32,39] and their concentrations increased in dynamics in non-survived patients [26], due to their production by pathobionts, such as Staphylococcus aureus, Klebsiella pneumonia, Acinetobacter baumanii, Pseudomonas aeruginosa, and Escherichia coli [40,41].…”

Section: Discussionmentioning

confidence: 95%

Serum and fecal profiles of aromatic microbial metabolites reflect gut microbiota disruption in critically ill patients: a prospective observational pilot study

et al. 2020

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Background: High serum levels of certain aromatic microbial metabolites (AMM) are associated with severity and mortality in critically ill patients. Omics-based studies suggest gut dysbiosis and reduced microbiome diversity in critical conditions. However, the landscape of gut microbial metabolites is still to be outlined, not to mention the interplay correlation between the metabolome and gut microbiome in critically ill patients. The aim of this study was to analyze the association between serum and fecal levels of AMM and compare them with the composition of gut microbiota in critically ill patients in the acute and chronic stages. Methods: In this prospective observational pilot study, we analyzed the temporal dynamics of the gut microbiome and the AMM spectrum across two distinct subgroups-acute critical ill (ACI) patients with nosocomial pneumonia and chronically critically ill (CCI) patients (9 subjects each group)-as well as performed comparison with 23 healthy volunteers. The AMM levels for each patient were measured using GC-MS in simultaneously taken serum and fecal samples (SFS). These parameters were compared with 16S rRNA fecal microbiome profiles. Results: The observed proportions of bacterial taxa suggest a significant gut dysbiosis in the ACI and the CCI patients. Stronger imbalance in microbiome composition and dynamics observed in the ACI patients compared to the CCI ones resonates with a higher severity in the former group. The total levels of AMM in serum samples were higher for the ACI patients than for the CCI patients (3.7 (1.4-6.3) and 1.1 (1.0-1.6) μM, respectively; p = 0.0003). The qualitative composition of the SFS was also altered. We discovered significant associations between gut microbial taxa levels and metabolite concentrations in blood serum as well as in feces in each of the ACI and the CCI patients. Conclusions: Aromatic microbial metabolite profiles in the gut and the serum are interlinked and reflect a disruption of the gut microbial community in critically ill patients.

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Section: Discussionmentioning

confidence: 95%

Serum and fecal profiles of aromatic microbial metabolites reflect gut microbiota disruption in critically ill patients: a prospective observational pilot study

et al. 2020

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“…[25,26]. The highest levels of these PhCAs are detected in the serum of patients with multiple organ dysfunction syndrome in sepsis [26,27,28]. These metabolites can come from both sources: the local focus of infection and intestinal bacteria [26,29,30].…”

Section: Introductionmentioning

confidence: 99%

“…Critical conditions are known to be accompanied by intestinal failure, which leads to a reduction in bacterial diversity and an accumulation of mostly gram-negative microorganisms, which are the main producers of the PhCAs [31]. The sum of three PhCAs reflects the disease severity as do the conventional scales Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential (Sepsis-related) Organ Failure Assessment (SOFA) [27,28]. The PhCA concentrations are demonstrated to increase in dynamics in non-survived patients while they decrease gradually in critical surviving patients [32].…”

Section: Introductionmentioning

confidence: 99%

Serum Levels of Mitochondrial and Microbial Metabolites Reflect Mitochondrial Dysfunction in Different Stages of Sepsis

et al. 2019

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Mechanisms of mitochondrial dysfunction in sepsis are being extensively studied in recent years. During our study, concentrations of microbial phenolic acids and mitochondrial metabolites (succinic, α-ketoglutaric, fumaric, itaconic acids) as indicators of sepsis and mitochondrial dysfunction, respectively, are measured by gas chromatography–mass spectrometry (GC–MS) in the blood of critically ill patients at the early and late stages of documented sepsis. The increase in levels of some phenylcarboxylic (phenyllactic (PhLA), p-hydroxyphenylacetic (p-HPhAA), p-hydroxyphenyllactic (p-HPhAA)) acids (PhCAs), simultaneously with a rise in levels of mitochondrial dicarboxylic acids, are mainly detected during the late stage of sepsis, especially succinic acid (up to 100–1000 µM). Itaconic acid is found in low concentrations (0.5–2.3 µM) only at early-stage sepsis. PhCAs in vitro inhibits succinate dehydrogenase (SDH) in isolated mitochondria but, unlike itaconic acid which acts as a competitive inhibitor of SDH, microbial metabolites most likely act on the ubiquinone binding site of the respiratory chain. A close correlation of the level of succinic acid in serum and sepsis-induced organ dysfunction is revealed, moreover the most significant correlation is observed at high concentrations of phenolic microbial metabolites (PhCAs) in late-stage sepsis. These data indicate the promise of such an approach for early detection, monitoring the progression of organ dysfunction and predicting the risk of non-survival in sepsis.

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“…It is shown that the AMM level relects the severity of the infectious process and is directly correlated with the number of clinical signs of inlammation, indicators of severity APACHEII and SOFA scores [24].…”

Section: Bacterial Load and Neutrophilsmentioning

confidence: 99%

Interaction of Host‐Microbial Metabolism in Sepsis

Владимировна¹

2017

Sepsis

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The majority of species of the human gut microbiota is not cultivated on artiicial nutrient media, but they are included in the functioning of microbial metabolic conveyor. Between the numerous gut bacteria (transmiter) and billions of intracellular mitochondria (receiver), the function of signaling molecules performs aromatic metabolites. Sepsis destroys the coordinated work of the indigenous anaerobic microlora. This leads to the imbalance of aromatic microbial metabolites (AMM). We hypothesized and proved diagnostic and pathogenic signiicance of this. First, deiciency of the end products of microbial metabolism-lipophilic AMM (PhPA and derivatives-cinnamic and benzoic acids) in sepsis, and second, excessive accumulation in blood of intermediate products named, "sepsis-associated" AMM-both lead to the development of mitochondrial dysfunction. Particularly, the total suppressed production of mROS can manifest by "hibernate-like state" of cells and lead to MOF. The participation of aromatic metabolites in the development of septic shock can be explained by the inhibition of tyrosine hydroxylase and impaired synthesis of catecholamines. In clinical research, the high levels of "sepsis-associated" AMM (p-HPhAA, p-HPhLA, and PhLA) correlate with the severity according to APACHE II, Sepsis-related Organ Failure Assessments (SOFA) score and mortality. To improve the survival of ICU patients, requires more atention to the role of imbalance of microbial metabolites in sepsis.

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Phenylcarboxylic Acids in The Assessment of The Severity of Patient Condition and The Efficiency of Intensive Treatment in Critical Care Medicine

Cited by 19 publications

References 0 publications

Serum and fecal profiles of aromatic microbial metabolites reflect gut microbiota disruption in critically ill patients: a prospective observational pilot study

Serum and fecal profiles of aromatic microbial metabolites reflect gut microbiota disruption in critically ill patients: a prospective observational pilot study

Serum Levels of Mitochondrial and Microbial Metabolites Reflect Mitochondrial Dysfunction in Different Stages of Sepsis

Interaction of Host‐Microbial Metabolism in Sepsis

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