Serum Aromatic Microbial Metabolites as Biological Markers in Intensive Care

Abstract

Thanks to modern technical solutions and advances in the field of metabolomic research, it has become possible to search for new biomarkers among low-molecular compounds, including microbial origin. In intensive care, the most urgent and unresolved problem is the syndrome of systemic inflammatory reaction, one way or another associated with bacteria, for example, complications of artificial lung ventilation, postoperative complications, attachment of multiple organ failure (sepsis), etc. Therefore, among a wide range of small molecules, metabolites of aromatic amino acid (tyrosine, phenylalanine) are of the greatest interest, since the metabolic pathways leading to their accumulation or disposal are closely interrelated in the human body with the human microbiota.Over the past two decades, in clinical studies, results of the search for metabolites of microbial origin using GC-MS were obtained in various groups of critical patients with pneumonia, abdominal sepsis, septic shock, infection complication in cardio surgery, neuro surgery, etc. The data indicate a high diagnostic and prognostic significance of some aromatic microbial metabolites (AMM), such as 4-hydroxyphenyl lactic acid (HPhLA), 4-hydroxyphenyl acetic acid (HPhAA), phenyllactic acid (PhAA). Serum AMM level in sepsis was not inferior and even had advantages over such well-known biomarkers as PCT or lactate, and was comparable in importance to multi-parametric severity scales such as SOFA. The use of AMM to predict the outcome of patients admitted to the intensive care unit is no less reliable than the widespread multi-parametric APACHE II scale.In vitro experimental studies have confirmed the ability of human microbiota bacteria to produce and consume the abovementioned, clinically significant aromatic metabolites; a decrease in the biodiversity of the microbiota and its metabolic function leads to an excess of AMM in the blood.In intensive care, AMM can be used to assess the severity of patients’ condition and the risk of death, to predict complications in big surgery (abdominal, cardiac, neurosurgery, etc.), as well as to monitor the effect of treatment.Today, the serum level of AMM is determined using GC-MS, HPLC-MS, etc. For widespread implementation in intensive care units, an accessible express method is needed, which will help improve results in patients with life-threatening diseases and sepsis.KeywordsSepsisShockMortalityMicrobiotaSystemic InflammationBiomarkerAromatic microbial metabolitesPhenylcarboxylic acidsPhenyllactic acidp-Hydroxyphenylacetic acidp-Hydroxyphenyllactic acidGas chromatography - Mass spectrometryPrognosis in intensive care