Rational bioinformatic approach to the analysis of functional properties of metabolites of probiotic microorganisms based on gene network reconstruction

An important direction in industrial microbiology is the development of probiotic strains with valuable consumer properties. The probiotic industry is currently one of the most rapidly developing segments of the food and pharmaceutical sectors. Stearic (octadecanoic) acid C18:0 is one of the major metabolites present in the cell-free supernatant of the bacterium Streptococcus thermophilus, which is widely used in the production of fermented dairy products, including yogurt and cheese. S. thermophilus affects not only the texture and sensory properties of products, but also exhibits various probiotic effects, including antioxidant activity, modulation of the gut microbiota, inhibition of certain pathogens, and others. It is assumed that a number of probiotic effects exerted by S. thermophilus may be mediated through octadecanoic acid as one of its main metabolites. Octadecanoic acid C18:0, like other long-chain fatty acids, enters the human body via several mechanisms, including protein-mediated transport and passive diffusion across cell membranes. Inside the cell, octadecanoic acid serves not only as a substrate for the synthesis of triglycerides and other complex lipids, but, as shown in cell-based and in vivo models, also acts as a modulator of signaling and stress responses, including those associated with apoptosis. This is an important aspect of the influence of stearic acid on organism functioning, underpinning its anti-inflammatory and potentially anti-tumor effects. However, the molecular genetic mechanisms by which octadecanoic acid acts as a probiotic on the human organism remain insufficiently understood. In the present study, using our previously developed information – software system ANDSystem (employing machine learning and artificial intelligence for automatic extraction of knowledge from scientific texts and databases), we reconstructed gene networks regulating the intrinsic (mitochondrial) and extrinsic (death receptor-mediated) apoptotic pathways in human cells under the influence of stearic (octadecanoic) acid. To search for metabolites produced by probiotic microorganisms that may have beneficial therapeutic properties, we propose an approach that combines gene network reconstruction with differential gene expression analysis. Using this approach, we show that octadecanoic acid produced by S. thermophilus can control the intrinsic and extrinsic apoptotic pathways primarily via regulation of PTGS2 expression; the results indicate that cyclooxygenase-2 is a key regulator mediating the effect of octadecanoic acid on apoptosis-related genes.

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