METABOLIC DYSBIOSIS OF THE GUT MICROBIOTA AND ITS BIOMARKERS

Abstract

Existing methods of clustering of gut microbiota (enterotypes, clusters, gradients), as well as the term 'phylogenetic core' do not reflect its functional activity. The authors propose to describe the key microbiora using term 'phylometabolic core of intestinal microbioca which more accurately reflects the functional importance of metabolically active microbiota. Phylometabolic core includes functional groups of microorganisms that perform similar metabolic functions: butyrate-producing bacteria, propionate-producing bacteria, acetate-produc- ing bacteria (acerogens), hydrogenosrophic microorganisms (reductive acetogens, sulfate-reducing bacteria, methanogens), lactate-producing and lactate-utilizing bacteria, bacteria involved in bile acids metabolism, bacteria that metabolize proteins and amino acids, vitamin-producing microorganisms, oxalate-degrading bacteria and others. The hypothesis that disturbance of microbial metabolism is the root of many human diseases is discussed. The microbial dysmexabo- lism leads to the metabolic dysbiosis (a particular form of dysbiosis) that is primarily characterized by metabolic abnormalities (e.g. serum, urinary, fetal or exhaled air). Metabolic dysbiosis is not necessarily accompanied by appreciable quantitative and/or qualitative changes in microbiora composition that called taxonomic dysbiosis. Since in the metabolic dysbiosis metabolic pathways can be switched only, it means the need for completely different approaches to its assessment using metabolomics (metabolic fingerprinting, metabolic profiling, meta-metabolomics). Metabolites concentrations in colon (feces, biopsy samples), blood (serum, plasma), urine or exhaled air, as well as metabolic profiles of examined substrates can serve as biomarkers. The main clinical variants of metabolic dysbiosis are due to the disturbances in microbial synthesis of short-chain fatty acids (primarily butyrate and propionate) and due to increasing bacterial production of hydrogen sulfide, ammonia and secondary bile acids (particularly deoxycholic acid). These kinds of metabolic dysbiosis can eventually lead to inflammatory bowel disease (IBD) or colorectal cancer (CRC). The metabolic dysbiosis due to bacterial choline dysmetabolism followed by overproduction of trimethylamine (TMA), arherogenic precursor of trimethylamine N-oxide (TMAO), is associated with atherogenesis and increased risk of cardiovascular disease. Dysmetabolism of aromatic amino acids leads to changes in the microbial production of phenylalanine and tyrosine derivatives (phenyl carboxylic acid, p-cresol) and tryptophan indole derivatives (indole carboxylic acid, indole) and contributes to pathogenesis in lBS. IBD, CRC, chronic liver and kidney diseases, cardiovascular diseases, autism and schizophrenia. Metabiotics, a new class of therapeutic agents, e.g. based on microbial metabolites, can correct metabolic dysbiosis, prevent diet- and microbiota-relared diseases and increase the effectiveness of treatment.