State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, National Clinical Research Center for Oral Diseases, Sichuan University, 610041, Chengdu, China.
Department of Operative Dentistry and Endodontics, West China School of Stomatology, Sichuan University, 610041, Chengdu, China.
NPJ Biofilms Microbiomes. 2023 Jul 17;9(1):49. doi: 10.1038/s41522-023-00417-0.
Periodontitis is the most important cause of tooth loss in adults and is closely related to various systemic diseases. Its etiologic factor is plaque biofilm, and the primary treatment modality is plaque control. Studies have confirmed that Fusobacterium nucleatum can cause periodontitis through its virulence factors and copolymerizing effects with other periodontal pathogens, such as the red complex. Inhibiting F. nucleatum is an essential target for preventing periodontitis. The time-consuming and costly traditional periodontal treatment, periodontal scaling, and root planing are a significant burden on individual and public health. Antibiotic use may lead to oral microbial resistance and microbiome imbalance, while probiotics regulate microbial balance. Akkermansia muciniphila is a critical probiotic isolated from the human intestine. It can protect the integrity of the epithelial barrier, regulate and maintain flora homeostasis, improve metabolism, and colonize the oral cavity. Its abundance is inversely correlated with various diseases. We hypothesized that A. muciniphila could inhibit the effects of F. nucleatum and alleviate periodontitis. Bacterial co-culture experiments showed that A. muciniphila could inhibit the expression of the virulence gene of F. nucleatum. After treating gingival epithelial cells (GECs) with F. nucleatum and A. muciniphila, transcriptome sequencing and ELISA experiments on medium supernatant showed that A. muciniphila inhibited the inflammatory effect of F. nucleatum on GECs by inhibiting TLR/MyD88/NF-κB pathway modulation and secretion of inflammatory factors. Finally, animal experiments demonstrated that A. muciniphila could inhibit F. nucleatum-induced periodontitis in BALB/c mice.
牙周炎是成年人牙齿缺失的最重要原因,与各种系统性疾病密切相关。其病因是菌斑生物膜,主要治疗方式是控制菌斑。研究证实,具核梭杆菌可以通过其毒力因子和与其他牙周致病菌(如红色复合体)的共聚作用引起牙周炎。抑制具核梭杆菌是预防牙周炎的重要目标。传统的牙周治疗,如牙周刮治和根面平整,耗时且费用昂贵,给个人和公共健康带来了巨大负担。抗生素的使用可能导致口腔微生物耐药和微生物组失衡,而益生菌则调节微生物平衡。阿克曼氏菌是从人类肠道中分离出来的一种重要益生菌。它可以保护上皮屏障的完整性,调节和维持菌群的平衡,改善代谢,并定植于口腔。其丰度与各种疾病呈负相关。我们假设阿克曼氏菌可以抑制具核梭杆菌的作用,从而缓解牙周炎。细菌共培养实验表明,阿克曼氏菌可以抑制具核梭杆菌毒力基因的表达。用具核梭杆菌和阿克曼氏菌处理牙龈上皮细胞(GECs)后,对培养基上清液进行转录组测序和 ELISA 实验表明,阿克曼氏菌通过抑制 TLR/MyD88/NF-κB 通路的调节和炎症因子的分泌,抑制了具核梭杆菌对 GECs 的炎症作用。最后,动物实验证明阿克曼氏菌可以抑制 BALB/c 小鼠中具核梭杆菌诱导的牙周炎。