Enterobactin inhibits microbiota-dependent activation of AhR to promote bacterial sepsis in mice.

Sepsis is a major cause of morbidity and mortality, but our understanding of the mechanisms underlying survival or susceptibility is limited. Here, as pathogens often subvert host defence mechanisms, we hypothesized that this might influence the outcome of sepsis. We used microbiota analysis, faecal microbiota transplantation, antibiotic treatment and caecal metabolite analysis to show that gut-microbiota-derived tryptophan metabolites including indoles increased host survival in a mouse model of Serratia marcescens sepsis.

Influence of the Microbial Metabolite Acetyl Phosphate on Mitochondrial Functions Under Conditions of Exogenous Acetylation and Alkalization.

Background: Acetyl phosphate (AcP) is a microbial intermediate involved in the central bacterial metabolism. In bacteria, it also functions as a donor of acetyl and phosphoryl groups in the nonenzymatic protein acetylation and signal transduction. In host, AcP was detected as an intermediate of the pyruvate dehydrogenase complex, and its appearance in the blood was considered as an indication of mitochondrial breakdown.

Common Mitochondrial Targets of Curcumin and Cinnamic Acid, the Membrane-Active Natural Phenolic Compounds.

Research has shown the multiple actions of curcumin on different cell systems, including enzymes and mitochondria. The detected effects of curcumin on mitochondria are diverse, ranging from protective to toxic. In this present work, the influence of curcumin, as well as cinnamic acid, which is a microbial metabolite and a possible product of the microbial breakdown of curcumin, on isolated mitochondria, was investigated.

Analysis of 4-Hydroxyphenyllactic Acid and Other Diagnostically Important Metabolites of α-Amino Acids in Human Blood Serum Using a Validated and Sensitive Ultra-High-Pressure Liquid Chromatography-Tandem Mass Spectrometry Method.

The profile of and dynamic concentration changes in tyrosine, phenylalanine, and tryptophan metabolites in blood are of great interest since they could be considered potential biomarkers of different disorders. Some aromatic metabolites, such as 4-hydroxyphenyllactic, 4-hydroxyphenylacetic, phenyllactic, and 4-hydroxybenzoic acids have previously demonstrated their diagnostic significance in critically ill patients and patients with post-COVID-19 syndrome. In this study, a sensitive method, including serum protein precipitation with methanol and ultra-high-pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) detection, was developed and validated for six phenyl- and five indole-containing acids in human serum.

Bacteriophage Cocktails in the Post-COVID Rehabilitation.

Increasing evidence suggests that gut dysbiosis is associated with coronavirus disease 2019 (COVID-19) infection and may persist long after disease resolution. The excessive use of antimicrobials in patients with COVID-19 can lead to additional destruction of the microbiota, as well as to the growth and spread of antimicrobial resistance. The problem of bacterial resistance to antibiotics encourages the search for alternative methods of limiting bacterial growth and restoring the normal balance of the microbiota in the human body.

Multivariate Prognostic Model for Predicting the Outcome of Critically Ill Patients Using the Aromatic Metabolites Detected by Gas Chromatography-Mass Spectrometry.

A number of aromatic metabolites of tyrosine and phenylalanine have been investigated as new perspective markers of infectious complications in the critically ill patients of intensive care units (ICUs). The goal of our research was to build a multivariate model for predicting the outcome of critically ill patients regardless of the main pathology on the day of admission to the ICU. Eight aromatic metabolites were detected in serum using gas chromatography-mass spectrometry.

4-Hydroxyphenyllactic Acid in Cerebrospinal Fluid as a Possible Marker of Post-Neurosurgical Meningitis: Retrospective Study.

The search for new potential biomarkers for the diagnostics of post-neurosurgical bacterial meningitis is required because of the difficulties in its early verification using results of the routine laboratory and biochemical analyses of the cerebrospinal fluid (CSF). The goal of the study was to determine the contents of the aromatic metabolites and biomarkers in the CSF samples of the post-neurosurgical patients ( = 82) and their potential diagnostical significance for the evaluation of the risk of post-neurosurgical meningitis. Patients with signs of post-neurosurgical meningitis ( = 30) had lower median values of glucose and higher values of cell count, neutrophils, lactate, protein, 3-(4-hydroxyphenyl)lactic acid (-HPhLA), and interleukin-6 (IL-6) than patients without signs of post-neurosurgical meningitis ( = 52).

Indolic Structure Metabolites as Potential Biomarkers of Non-infectious Diseases.

Interest in indolic structure metabolites, including a number of products of microbial biotransformation of the aromatic amino acid tryptophan, is increasingly growing. The review prepared by a team of authors is based on in-depthscrutiny of data available in PubMed, Scopus, Cyberleninka, Clinical Trials, and Cochrane Library, eventually narrowing the search to a set of keywords such as tryptophan metabolites; plasma metabolomics profiling; metabolomics fingerprinting; gas-, liquid chromatography mass spectrometry; serotonin; melatonin; tryptamine; indoxyl sulfate; indole-3-acetic acid; indole-3-propionic acid; 5-hydroxyindole-3-acetic acid; gut microbiota and microbial metabolites. It provides a summary that outlines the pattern of changes in the level of indolic structure metabolites in a number of diseases and deals with the data from the field of human microbiota metabolites.

Metabolic profiling of aromatic compounds in cerebrospinal fluid of neurosurgical patients using microextraction by packed sorbent and liquid-liquid extraction with gas chromatography-mass spectrometry analysis.

A new approach to the quantitative analysis of aromatic metabolites in cerebrospinal fluid samples of neurosurgical patients based on microextraction by packed sorbent coupled with derivatization and GC-MS was developed. Analytical characteristics such as recoveries (40-90%), limit of detection (0.1-0.

Involvement of Aromatic Metabolites in the Pathogenesis of Septic Shock.

Introduction: We hypothesized that aromatic microbial metabolites (AMM), such as phenyllactic (PhLA), p-hydroxyphenylacetic (p-HPhAA), and p-hydroxyphenyllactic (p-HPhLA) acids, contribute to the pathogenesis of septic shock.

Methods: Clinical and laboratory data of patients with community-acquired pneumonia were obtained on intensive care unit admission and the next day. Patients were divided into two groups based on septic shock presence or absence.

Metabolomic findings in sepsis as a damage of host-microbial metabolism integration.

Metabolomics globally evaluates the totality of the endogenous metabolites in patient's body, at the same time reflecting gene function, enzyme activity and degree of organ dysfunction in sepsis. The authors performed the analysis of the main chemical classes of low molecular weight compounds (amino acids, polyols, fatty acids, hydroxy acids, amines, nucleotides and their derivatives) that quantitatively distinguish patients with sepsis from healthy ones. The following keywords were used to find papers published in the Scopus and Web of Science databases from 2008 to 2015: (marker OR biomarker) AND (sepsis OR critical ill OR pneumonia OR hypoxia).

Management of familial Mediterranean fever by colchicine does not normalize the altered profile of microbial long chain fatty acids in the human metabolome.

In our previous works we established that in an autoinflammatory condition, familial Mediterranean fever (FMF), the gut microbial diversity is specifically restructured, which also results in the altered profiles of microbial long chain fatty acids (LCFAs) present in the systemic metabolome. The mainstream management of the disease is based on oral administration of colchicine to suppress clinical signs and extend remission periods and our aim was to determine whether this therapy normalizes the microbial LCFA profiles in the metabolome as well. Unexpectedly, the treatment does not normalize these profiles.

Profiles of Microbial Fatty Acids in the Human Metabolome are Disease-Specific.

The human gastrointestinal tract is inhabited by a diverse and dense symbiotic microbiota, the composition of which is the result of host-microbe co-evolution and co-adaptation. This tight integration creates intense cross-talk and signaling between the host and microbiota at the cellular and metabolic levels. In many genetic or infectious diseases the balance between host and microbiota may be compromised resulting in erroneous communication.