Biotech Research Institute, Grape King Bio Ltd, Taoyuan City 325, Taiwan.
Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei City 110, Taiwan.
J Microbiol Biotechnol. 2024 Oct 28;34(10):2079-2090. doi: 10.4014/jmb.2402.02013. Epub 2024 Jul 31.
In response to the growing demand for immune-related products, this study evaluated the safety and immune-modulating potential of three newly discovered strains (GKM3, GKK1, and GKD7) through toxicity tests and whole-genome sequencing. Safety evaluations, including the analysis of antimicrobial resistance genes, virulence factors, plasmids, and prophages, classified these strains as safe for human consumption. Acute oral toxicity tests further supported their safety. To evaluate their immune-modulating potential, dendritic cells were exposed to these strains, and the secretion of key cytokines (IFN-β and IL-12) was measured. Among the strains, GKK1 exhibited the highest enhancement of IFN-β and IL-12 production, suggesting its potential as an immune-stimulating probiotic. Bioinformatics analysis revealed potential metabolic pathways and secondary metabolites, including predicted bacteriocins, associated with immune modulation. The presence of a nitrate reductase region in the GKK1 strain indicated its ability to produce nitric oxide, a critical molecule involved in immune regulation and host defense. The presence of glucorhamnan-related gene clusters in GKK1 also suggested immune-enhancing effects. Nitrate reductase expression was confirmed using qPCR, with the highest levels detected in GKK1. Moreover, this study is the first to show an anti-inflammatory effect of plantaricin A, linked to its presence in strain GKM3 and its potential therapeutic applications due to sequence similarity to known anti-inflammatory peptides. Overall, these three strains demonstrated a safe profile and GKK1 showed potential as an immunity-enhancing probiotic. However, additional investigation is required to confirm the involvement of specific metabolic pathways, secondary metabolites, and bacteriocins in immune responses.
针对不断增长的免疫相关产品需求，本研究通过毒性测试和全基因组测序，评估了三种新发现的菌株（GKM3、GKK1 和 GKD7）的安全性和免疫调节潜力。安全性评估包括对抗菌药物耐药基因、毒力因子、质粒和噬菌体的分析，将这些菌株归类为可安全用于人类食用。急性口服毒性测试进一步支持了它们的安全性。为评估它们的免疫调节潜力，将树突状细胞暴露于这些菌株中，并测量关键细胞因子（IFN-β和IL-12）的分泌。在这些菌株中，GKK1 表现出最高的 IFN-β和 IL-12 产生增强作用，表明其作为免疫刺激益生菌的潜力。生物信息学分析揭示了潜在的代谢途径和次级代谢产物，包括预测的细菌素，与免疫调节相关。GKK1 菌株中存在硝酸盐还原酶区域表明其能够产生一氧化氮，这是一种参与免疫调节和宿主防御的关键分子。GKK1 中存在葡聚糖相关基因簇也表明其具有增强免疫的作用。使用 qPCR 证实了硝酸盐还原酶的表达，在 GKK1 中检测到最高水平。此外，本研究首次表明了植物乳杆菌 A 的抗炎作用，这与其在 GKM3 菌株中的存在以及由于与已知抗炎肽的序列相似性而具有的潜在治疗应用有关。总的来说，这三种菌株表现出安全的特性，GKK1 作为一种增强免疫力的益生菌具有潜力。然而，需要进一步研究来确认特定代谢途径、次级代谢产物和细菌素在免疫反应中的参与。
