ABSTRACT: In recent years, there has been an increasing tendency to create drugs of various types based on certain commensal bacteria of the human microbiota and their ingredients. This primarily concerns live biotherapeutics (LBPs) and postbiotics. The creation of such drugs, which can be called pharmacobiotics, requires an understanding of the mechanisms of their action and the identification of pharmacologically active ingredients that determine their target properties. As a rule, this is a complex of biologically active substances synthesized by a specific strain, promoted as LBP or postbiotics (including vesicles): proteins, enzymes, low molecular weight metabolites, small RNAs, etc. In this article, we, primarily targeting neuroinflammatory processes, explore the potential of omics technologies, including genomics, proteomics, transcriptomics, and metabolomics, in harnessing the potential of Limosilactobacillus fermentum U-21 for the development of innovative LBP and postbiotic formulations. Metabolomics and proteomics were employed to elucidate the underlying mechanisms governing the unique attributes of L.fermentum U-21, with particular emphasis on the potential for utilizing its vesicles in postbiotic production. This study utilizes cutting-edge proteomic techniques to identify and quantify the proteins expressed, shedding light on their functional attributes and potential applications. Furthermore, metabolomic analysis provides valuable insights into the small-molecule metabolites produced during fermentation, which made it possible to detect compounds with anti-neuroinflammatory activity. As a result, metabolites and proteins potentially responsible for the immunomodulatory, anti-neuroinflammatory and neuromodulatory activities that were detected in the strain in previous experiments, were identified, including in vesicles. We have shown that L.fermentum U-21 is capable of synthesizing: GABA, Niacin, cyclo(Leu-Gly), Aucubin, chaperone proteins with potential disaggregase activity, and the chemical chaperone scyllo-inositol.
Olga Tikhonova 
