Probiotic activity of <i>Bacillus subtilis</i> metabolites in experimentally induced dysbiosis in mice

S. А. Lazarev, N. O. Vartanova, A. V. Poddubikov, N. A. Mikhailova
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Abstract

Scientific relevance . A promising option for dysbiosis correction is the use of metabiotics, products based on metabolites of probiotic microorganisms. During fermentation, Bacillus subtilis bacteria (strains 3H and 1719) produce metabolites that exhibit probiotic properties in vitro . These observations in vitro motivate an in vivo investigation of B. subtilis metabolite effects on colonic mucosal microbiota in mice in experimentally induced dysbiosis and an assessment of the potential of B. subtilis metabolites as metabiotics. Aim . The authors aimed to compare the probiotic activity of B. subtilis 3H and B. subtilis 1719 metabolites and a commercial metabiotic in antibiotic-induced dysbiosis in mice. Materials and methods . The authors induced experimental dysbiosis in BALB/c mice weighing 18–20 g by intraperitoneal injection of gentamicin. For subsequent correction, the test groups received sorbent-bound B. subtilis metabolites, and the comparison group received a commercial metabiotic containing B. subtilis metabolites (VKPM B-2335(3)3) via intragastric injection for 21 days. The quantitative and qualitative analysis of colonic mucosal microbiota included microbial culturing and colony identification by MALDI-TOF mass spectrometry. Results . Antibiotic-induced colonic dysbiosis in mice manifested itself as a decrease in the dominant microbiota and an increase in opportunistic pathogens. After 7 days of metabolite administration, the Lactobacillus population returned to normal in all treatment groups. The mice that received B. subtilis 3H metabolites showed the best results: their Lactobacillus spp. composition corresponded to that of intact animals. The content of Lac+ Escherichia coli returned to 100% in all treatment groups. After 21 days of metabolite administration, the authors observed the elimination of bacteria ( Rodentibacter spp., Aerococcus spp.) and fungi ( Trichosporon spp., Kazachstania spp.) in the B. subtilis 3H group; Trichosporon spp. (no effect on Kazachstania spp.) in the B. subtilis 1719 group; and Enterococcus spp., Kazachstania spp., and Trichosporon spp. (no effect on Rodentibacter spp. and Aerococcus spp.) in the commercial metabiotic group. Conclusions . Metabolites of B. subtilis strains 3H and 1719 help to restore the diversity and abundance of colonic microbiota in antibiotic-induced dysbiosis. The differences observed in microbiota re-establishment in the treatment groups indicate that there is interstrain variability in the probiotic activity of B. subtilis metabolites.
枯草芽孢杆菌的益生菌活性实验诱导小鼠生态失调的代谢物
科学相关性。纠正生态失调的一个有希望的选择是使用代谢物,基于益生菌微生物的代谢物的产品。在发酵过程中,枯草芽孢杆菌(菌株3H和1719)在体外产生具有益生菌特性的代谢物。这些体外观察结果激发了在体内研究枯草芽孢杆菌代谢物对实验诱导的生态失调小鼠结肠粘膜微生物群的影响,并评估枯草芽孢杆菌代谢物作为代谢物的潜力。的目标。作者旨在比较枯草芽孢杆菌3H和枯草芽孢杆菌1719代谢物和商业代谢物在抗生素诱导的小鼠生态失调中的益生菌活性。材料和方法。作者通过腹腔注射庆大霉素诱导体重18-20 g的BALB/c小鼠实验性生态失调。为了进行后续校正,试验组给予吸收剂结合枯草芽孢杆菌代谢物,对照组给予含有枯草芽孢杆菌代谢物的商业代谢物(VKPM B-2335(3)3)灌胃注射,持续21天。结肠粘膜微生物群的定量和定性分析包括微生物培养和MALDI-TOF质谱鉴定。结果。抗生素诱导的小鼠结肠生态失调表现为优势菌群的减少和机会致病菌的增加。代谢物给药7 d后,各处理组乳酸杆菌数量均恢复正常。接受枯草芽孢杆菌3H代谢物的小鼠表现出最好的结果:它们的乳酸杆菌组成与未受影响的动物相当。各处理组Lac+大肠杆菌含量均恢复到100%。代谢产物给药21天后,作者观察到枯草芽孢杆菌3H组细菌(啮齿菌、气球菌)和真菌(Trichosporon、Kazachstania)的消除;枯草芽孢杆菌1719组中trichosporonspp(对Kazachstania spp无影响);商业代谢组对肠球菌、哈萨克斯坦球菌和毛磷菌(对啮齿杆菌和航空球菌没有影响)的抑制作用。结论。枯草芽孢杆菌菌株3H和1719的代谢物有助于在抗生素诱导的生态失调中恢复结肠微生物群的多样性和丰度。在处理组中观察到的微生物群重建的差异表明,枯草芽孢杆菌代谢物的益生菌活性存在菌株间变异。
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