Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology

Abstract

In the twenty-first century, metabolomics allowed evaluating the profile of metabolites of various classes of compounds in the human body. The most important achievement of the metabolic approach is to obtain evidence of the intersection of human biochemical pathways and its microbiota. The effect of certain microbial metabolites on the work of key enzymes involved in the biotransformation of amino acids and other substances becomes more important in patients at risk of developing neurological and mental disorders and also contributes to the development of life-threatening conditions up to multiple organ failure after operations, injuries, and serious diseases. The authors of this chapter call the microbiota an "invisible organ," emphasizing its functional significance, and not just taxonomy, as previously thought. This chapter will discuss the mutually beneficial integration of the metabolome/microbiome in the body of healthy people and will focus on the effects of microbiota dysfunction.

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

“…The following AMM are potentially involved in the pathological process: phenyllactic acid (PhLA), phenylpropionic acid (PhPA), phenylacetic acid (PhAA), p-hydroxyphenylacetic acid (p-HPhAA), and p-hydroxyphenyllactic (p-HPhLA) acid. АММ levels reflect the severity of the bacterial inflammatory process: they increase in patients with a local proinflammatory disease and reach a maximum level during severe sepsis and septic shock [12]. Our hypothesis regarding the bacterial origin of АММ was supported by the results obtained with isolates of clinically significant species of bacteria [13].…”

“Dialogue” between the Human Microbiome and the Brain

“…Tyrosine and tryptophan are two of the nine essential amino acids that cannot be synthesized in the human body. Various metabolic pathways of metabolism of aromatic amino acids, such as tyrosine and tryptophan, with different endogenous and microbial enzymes, have been previously described [1]. Most often, the products of microbial protein biodegradation are associated with negative or toxic effects [2,12].…”

“…Normally, the epithelialimmune-gut barrier supports homeostasis in the host body. The importance of the function of the gut microbiota for the host organism allows us to consider it as a large but "invisible organ" [1]. 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 [2,3].…”

“…Today, modern technologies allow us to identify hundreds of types of microorganisms in the human gut. Various microbial metabolites are also available for measurement in biological material samples, including feces, blood, urine, cerebrospinal fluid (CSF), and so on [1][2][3]. Thus, the possibilities of determining microbiota metabolites have expanded to studying their role both in healthy people and in patients with various diseases.…”

The role of human and microbial metabolites of triptophane in severe diseases and critical ill (review)

“…Образование производных триптофана происходит двумя основными путями, которые могут быть названы индольным и кинурениновым (рис. 1) [6]. Индольный путь превращения триптофана (условно делится на серотониновый и микробный) ведет к образованию нейротрансмиттера серотонина, «гормона сна» -мелатонина, а также целого ряда других метаболитов, содержащих индольное кольцо, например триптамина, который подвергается дальнейшей биотрансформации с образованием индолуксусной, индолпропановой кислот, индола и индоксила.…”