Brutscher Laura M, Borgmeier Claudia, Garvey Sean M, Spears Jessica L
BIO-CAT Microbials, LLC, Shakopee, MN 55379, USA.
BRAIN Biotech AG, 64673 Zwingenberg, Germany.
Microorganisms. 2022 May 17;10(5):1038. doi: 10.3390/microorganisms10051038.
Despite the commercial rise of probiotics containing spp., it remains important to assess the safety of each strain before clinical testing. Herein, we performed preclinical analyses to address the safety of BS50. Using in silico analyses, we screened the 4.15 Mbp BS50 genome for genes encoding known toxins, secondary metabolites, virulence factors, and antibiotic resistance. We also assessed the effects of BS50 lysates on the viability and permeability of cultured human intestinal epithelial cells (Caco-2). We found that the BS50 genome does not encode any known toxins. The BS50 genome contains several gene clusters involved in the biosynthesis of secondary metabolites, but many of these antimicrobial metabolites (e.g., fengycin) are common to spp. and may even confer health benefits related to gut microbiota health. BS50 was susceptible to seven of eight commonly prescribed antibiotics, and no antibiotic resistance genes were flanked by the complete mobile genetic elements that could enable a horizontal transfer. In cell culture, BS50 cell lysates did not diminish either Caco-2 viability or monolayer permeability. Altogether, BS50 exhibits a robust preclinical safety profile commensurate with commercial probiotic strains and likely poses no significant health risk to humans.
尽管含有 菌属的益生菌在商业上有所兴起，但在进行临床试验之前评估每种菌株的安全性仍然很重要。在此，我们进行了临床前分析以评估 BS50 的安全性。通过计算机分析，我们在 4.15 Mbp 的 BS50 基因组中筛选了编码已知 毒素、次生代谢产物、毒力因子和抗生素抗性的基因。我们还评估了 BS50 裂解物对培养的人肠上皮细胞（Caco-2）活力和通透性的影响。我们发现 BS50 基因组不编码任何已知的 毒素。BS50 基因组包含几个参与次生代谢产物生物合成的基因簇，但许多这些抗菌代谢产物（例如，丰原素）在 菌属中很常见，甚至可能带来与肠道微生物群健康相关的健康益处。BS50 对八种常用抗生素中的七种敏感，并且没有抗生素抗性基因两侧有能够实现水平转移的完整可移动遗传元件。在细胞培养中，BS50 细胞裂解物既没有降低 Caco-2 的活力也没有降低单层通透性。总体而言，BS50 表现出与商业益生菌菌株相当的强大临床前安全性，并且可能对人类不构成重大健康风险。
