Evgeniya Valer’evna Prazdnova, Vladimir Anatolevich Chistyakov, Nikita Gennadjevich Vasilchenko, Radomir Viktorovich Skripnichenko, Alina Yurievna Gulyaeva, Anna Valentinovna Aleshukina, Iraida Sergeievna Berezinskaya, and Dmitriy Vladimirovich Rudoy. Prev Nutr Food Sci 2025;30:274-84. https://doi.org/10.3746/pnf.2025.30.3.274

The development of probiotic and synbiotic preparations for aquaculture is of considerable practical importance. However, research in this field has typically focused on end-point effects, whereas the dynamics of the interactions between the probiotic, the host, and the intestinal bacterial communities remain insufficiently characterized. In this study, we evaluated the effect of a synbiotic supplement based on the Bacillus subtilis MT74 strain on the composition of the gut microbiota and gene expression in zebrafish (Danio rerio). Fish received either the synbiotic supplement or equivalent dietary doses of its individual components, namely Bacillus subtilis MT74 culture and inulin. Gut microbial community composition was assessed by 16S rRNA gene amplicon sequencing, and the expression of igf1, hsp70l, gsta.1, lyz, mt2, and b2m was evaluated on days 6, 15, and 30. In addition, the persistence of the studied strain in the gut microbiota after discontinuation of its dietary administration was evaluated. The results revealed multistage changes in gut microbiota composition and host gene expression profiles. These findings indicate that microbiome restructuring and stabilization during dietary intervention are dynamic processes accompanied by changes in host regulatory responses.

Bacillus-derived lipopeptides are known to possess diverse biological activities, including antimicrobial and anticancer properties, though the mechanisms of such effects at the molecular level remain incompletely understood. We investigated whether non-ribosomal peptide metabolites from Bacillus can directly interact with transmembrane receptors implicated in oxidative stress regulation and cancer progression (NOX4, EGFR, PDGFR, and OCTN2) using molecular docking and 200 ns molecular dynamics simulations of 11 lipopeptide metabolites. Molecular docking revealed several strong ligand–protein interactions, with plipastatin and fengycin emerging as lead compounds demonstrating the highest binding affinities to multiple receptors. For NOX4, iturin D showed the strongest docking score of −7.85 kcal/mol. Fengycin demonstrated a high docking score of −7.38 kcal/mol for PDGFR and −8.1 kcal/mol for EGFR. Plipastatin showed the strongest docking scores of −11.12 kcal/mol for EGFR and −8.7 kcal/mol for OCTN2. Molecular dynamics simulations confirmed complex stability for these lead compounds, with protein RMSD remaining stable at ~1.5 Å and ligand RMSD between 1.9 and 6 Å over 200 ns. Our findings suggest that plipastatin and fengycin may act as modulators of key receptors involved in oxidative stress and cancer-related signaling. However, those in silico predictions require experimental validation. This work provides the first computational evidence of potential lipopeptide–receptor interactions and establishes a foundation for future experimental investigation of probiotic-derived therapeutics.