Wang Peiling, Ma Rong, Ma Dandan, Lin Yisha, Wang Yimin, Zhang Yuanyuan, Chu Jinpu
The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
College of Stomatology, Zhengzhou University, Zhengzhou, 450052, China.
BMC Biol. 2025 Aug 22;23(1):262. doi: 10.1186/s12915-025-02321-9.
Intake of glucose and sucrose accelerates the development of dental caries in children. Scardovia wiggsiae (S. wiggsiae) is a potential pathogen of early childhood caries (ECC). Previous research conducted by our group has demonstrated that rubusoside, a non-cariogenic sweetener, inhibits the caries pathogen Streptococcus mutans (S. mutans). To investigate the effects of rubusoside as a sucrose substitute and sweet additive on the growth and metabolism of S.wiggsiae and to predict the underlying mechanisms.
The minimum inhibitory concentration (MIC) of rubusoside was determined to be 1% using the microdilution method. Both as a standalone agent and in combination with sucrose, rubusoside significantly inhibited the growth, acid-producing capability, and adhesion of S.wiggsiae. Utilizing techniques such as crystal violet staining, anthrone-sulfuric acid reaction, BCA protein quantification, scanning electron microscopy (SEM), and confocal laser scanning microscopy (CLSM), we demonstrated that rubusoside effectively suppressed the formation of S. wiggsiae biofilms and reduced the synthesis of extracellular polysaccharides (EPS) and soluble proteins. The whole genome sequencing of S. wiggsiae was conducted for the first time and combined with RNA-seq analysis, the potential mechanism of rubusoside inhibiting bacterial biofilm formation was predicted: It might exert bacteriostatic effects by influencing bacterial carbohydrate metabolic pathways (such as nucleotide sugar synthesis, amino sugar and nucleotide sugar metabolism, galactose metabolism, and phosphotransferase system), and downregulating the expression of virulence genes (clpP and groEL) related to adhesion, invasion, and biofilm formation.
Rubusoside exhibits a significant bacteriostatic effect against S. wiggsiae, a potential pathogen associated with early childhood dental caries. Notably, its inhibitory activity remains unaffected even in the presence of sucrose. Consequently, as a sucrose substitute or sweetener additive, rubusoside holds broad application prospects in both the food industry and oral hygiene products, offering a promising approach to the prevention and treatment of dental caries.
摄入葡萄糖和蔗糖会加速儿童龋齿的发展。斯氏韦永氏菌（S. wiggsiae）是幼儿龋齿（ECC）的一种潜在病原体。我们团队之前的研究表明，甜菊糖苷这种非致龋性甜味剂可抑制致龋病原体变形链球菌（S. mutans）。为了研究甜菊糖苷作为蔗糖替代品和甜味添加剂对斯氏韦永氏菌生长和代谢的影响，并预测其潜在机制。
采用微量稀释法测定甜菊糖苷的最低抑菌浓度（MIC）为1%。无论是作为单一药剂还是与蔗糖联合使用，甜菊糖苷均能显著抑制斯氏韦永氏菌的生长、产酸能力及黏附。利用结晶紫染色、蒽酮 - 硫酸反应、BCA蛋白定量、扫描电子显微镜（SEM）和共聚焦激光扫描显微镜（CLSM）等技术，我们证明甜菊糖苷能有效抑制斯氏韦永氏菌生物膜的形成，并减少细胞外多糖（EPS）和可溶性蛋白的合成。首次对斯氏韦永氏菌进行全基因组测序，并结合RNA - seq分析，预测了甜菊糖苷抑制细菌生物膜形成的潜在机制：它可能通过影响细菌碳水化合物代谢途径（如核苷酸糖合成、氨基糖和核苷酸糖代谢、半乳糖代谢及磷酸转移酶系统），并下调与黏附、侵袭和生物膜形成相关的毒力基因（clpP和groEL）的表达来发挥抑菌作用。
甜菊糖苷对与幼儿龋齿相关的潜在病原体斯氏韦永氏菌具有显著的抑菌作用。值得注意的是，即使在有蔗糖存在的情况下，其抑制活性也不受影响。因此，作为蔗糖替代品或甜味剂添加剂，甜菊糖苷在食品工业和口腔卫生产品中均具有广阔的应用前景，为龋齿的预防和治疗提供了一种有前景的方法。
