唾液联合乳杆菌在口腔疾病防治中的研究进展

Research progress on Ligilactobacillus salivarius in the prevention and treatment of oral diseases

口腔是人体中微生物定植最丰富的位点之一,维持其微生态的平衡能有效促进口腔健康。唾液联合乳杆菌(Ligilactobacillus salivarius)作为联合乳杆菌的一种,有着良好的口腔定植能力及改善口腔微生态以防治疾病的潜力。目前,唾液联合乳杆菌在口腔疾病中的应用及机制研究主要包括:通过直接抑制变异链球菌生长以及下调其致龋毒力因子葡萄糖基转移酶基因(glucosyltransferases,gtfs)表达,减少牙面黏附变异链球菌数量,防治龋病;减少牙周炎相关关键微生物,并减少伴放线菌团聚杆菌毒力因子细胞致死膨胀毒素B(cytolethal distending toxin B,CdtB)、白细胞毒素(leukotoxin,LtxA)表达,减轻牙周炎患者局部微生物刺激,同时,直接抑制巨噬细胞的丝裂原活化蛋白激酶(mitogen-activated protein kinases,MAPK)以及核因子NF-κB(nuclear factor NF-kappaB,NF-κB)通路激活进而抑制破骨作用,减轻牙周骨吸收;对于黏膜炎症,唾液联合乳杆菌可拮抗白色念珠菌,抑制致病性菌丝或胚管形成,防治念珠菌性口炎,还可减少金黄色葡萄球菌数量,并缓解其感染所致的巨噬细胞的toll样受体/磷脂酰肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白(toll-like receptor/phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin,TLR/PI3K/Akt/mTOR)信号通路和toll样受体/磷脂酰肌醇3-激酶/蛋白激酶B/kappa B抑制因子/核转录因子kappaB(toll-like receptor/phosphoinositide 3-kinase/protein kinase B/inhibitors of kappa B/nuclear factor kappa B,TLR/PI3K/Akt/IκB/NF-κB)通路激活,减轻口咽部炎症反应;通过对口腔肿瘤细胞体外研究发现,唾液联合乳杆菌可下调癌细胞蛋白激酶B/细胞周期蛋白D1(protein kinase B/cyclin D1,Akt/cyclin D1)表达,诱导肿瘤细胞的直接凋亡并降低环氧合酶-2(cyclooxygenase-2,COX-2)表达水平,改善肿瘤免疫抑制微环境。然而唾液联合乳杆菌变异多,需要更深入的研究以厘清具体菌株的临床功效、安全性及其治病机制。尽管新兴微生物研究技术已出现,但在唾液联合乳杆菌的应用尚较少。如何运用这些方法来研究唾液乳杆菌对口腔疾病的作用将是未来发展方向之一。本文对唾液联合乳杆菌在口腔领域的现存研究进行综述,以期为今后的研究提供参考。

The oral cavity harbors a diverse population of microorganisms,making it one of the most heavily colonized sites in the human body.Maintaining a balanced microecology is crucial for oral health.Ligilactobacillus salivarius as a species of Ligilactobacillus,has good oral colonization ability and potential to improve oral microecology for disease prevention and control.Currently,the application and mechanism of Ligilactobacillus salivarius in oral diseases include several aspects.First,by directly inhibiting the growth of Streptococcus mutans and downregulating the expression of its cariogenic virulence factor,gtfs,the aim is to reduce the number of adherent Streptococcus mutans on the tooth surface,thereby preventing dental caries.Second,reducing the number of keystone taxa in periodontitis,and the virulence factors of Aggregatibacter actinomycetemcomitans,including CdtB and LtxA,can alleviate local stimulation in patients with periodontitis.Additionally,directly inhibiting macrophage MAPK and NF-κB pathway activation suppresses osteoclastogenesis and reduces periodontal bone absorption.In mucosal inflammation,Ligilactobacillus salivarius competes with Candida albicans,inhibits the formation of pathogenic hyphae or germ tubes,and prevents monilial stomatitis.Ligilactobacillus salivarius can also reduce the amount of Staphylococcus aureus and mitigate the activation of the macrophage TLR/PI3K/Akt/mTOR and TLR/PI3K/Akt/IκB/NF-κB pathways induced by S.aureus infections,thus alleviating inflammation in the oral and pharyngeal regions.In vitro studies on oral tumors have revealed that Ligilactobacillus salivarius can downregulate the expression of cancer cell Akt/Cyclin D1,induce direct apoptosis of tumor cells,reduce COX-2 expression,and improve the tumor immune-suppressive microenvironment.Previous studies have revealed considerable variability in Ligilactobacillus salivarius,necessitating more detailed research to clarify its clinical effects,safety,and mechanisms.Despite the emergence of novel microbiological research techniques,their application to Ligilactobacillus salivarius remains relatively limited.One crucial direction for future research is to better utilize these methods to investigate the effects of Ligilactobacillus salivarius on oral diseases.Considering these factors,this study provides a comprehensive review of existing research studies on Ligilactobacillus salivarius in the fields of oral medicine and dentistry,with the aim to serve as a reference and guide for future studies.