口腔真菌群落多样性时空演替与低龄儿童龋发病关系的队列研究

Dental caries is the most common chronic disease in children, and oral microorganism is the initiating factor. Searching for microbiological markers related to caries risk is the key to achieve ecological prevention and treatment of dental caries. Fungal community is an important component of oral microecology, and its diversity is second only to bacteria. Studies have shown that the detection of Candida albicans can significantly increase the risk of early childhood caries, suggesting that oral fungi play an important role in it. However, the relationship between dental caries and other fungi in the oral cavity is still lack of research. Previous studies showed that there were significant differences in the composition and diversity of oral fungal community between 3-year-old caries children and non-caries-free children, suggesting the composition and diversity of oral fungi community in children with dental caries. The changes may be closely related to the occurrence and development of caries. In this study, a 2-year prospective cohort study was conducted in 3-year-old children. High-throughput sequencing and bioinformatics techniques were used to analyze the temporal-spatial succession of dental plaque and saliva fungal community and its relationship with dental caries in young children. The interaction model of oral fungal core bacteria was revealed by constructing a covariant network of fungal flora, and the effects of saliva environmental factors on oral fungal community were discussed. This study may provide a theoretical basis for elucidating the role of oral fungal group in the steady-state maintenance of oral health and its relationship with early childhood caries and improving the risk assessment system for dental caries.

龋病是儿童最常见的慢性疾病，口腔微生物是其始动因素，寻找龋风险相关微生物标志，是实现龋病生态防治关键。真菌群落是口腔微生态的重要组分，多样性仅次于细菌。近年发现白假丝酵母菌检出可显著增高儿童患龋风险，提示口腔真菌在儿童龋发病中的重要作用。但口内其他真菌与龋病的关系目前尚缺乏研究。申请人前期研究发现，3岁有龋儿童较无龋儿童口腔真菌群落组成存及多样性存在显著差异，推测儿童口腔真菌群落组成及多样性动态变化可能与龋病发生发展密切相关。本项目拟对3岁儿童开展2年期的前瞻性队列研究，运用高通量测序及生物信息学技术分析口腔牙菌斑及唾液真菌群落组成及多样性时空演替规律及其与低龄儿童龋的关系；通过构建真菌菌群共变异网络，揭示口腔真菌核心菌属间的相互作用模式；探讨唾液环境因子对口腔真菌群落的影响。本项目可为阐明口腔真菌组在口腔康稳态维持中的作用及其与儿童龋的关系，健全龋风险评估体系提供理论依据。

龋病是儿童最常见的慢性疾病，口腔微生物是其始动因素，寻找龋风险相关微生物标志，是实现龋病生态防治关键。真菌群落是口腔微生态的重要组分，多样性仅次于细菌。近年发现白假丝酵母菌检出可显著增高儿童患龋风险，提示口腔真菌在儿童龋发病中的重要作用。本项目通过横断面研究和为期2年的纵向研究，运用高通量测序及生物信息学技术分析证实，从无龋向低龄儿童龋转变的过程中儿童口腔真菌群落组成存及多样性存在显著差异与变化。患龋儿童健康牙面菌斑真菌群落多样性和丰富度均高于龋损牙面菌斑样本和龋损组织样本，表明真菌群落Alpha多样性的降低可能与龋病进展相关；研究还发现白假丝酵母菌的相对丰度在低龄儿童龋儿童的健康牙面、龋损牙面和龋损组织中依次增加，证实白假丝酵母菌在龋病进展中发挥重要作用。口腔真菌群落的环境因子关联分析表明铁、氟浓度对细菌、真菌群落结构变化并无显著相关性；黑孢菌属、念珠菌属、纤孔菌属等真菌与低pH值或局部菌斑产酸能力的增强相关；构建真菌菌群共变异网络发现不论是在健康还是龋病状态，口腔真菌菌种间均存在复杂的交互作用网络，真菌与真菌间多数为正相关关系，在疾病或健康状态发生转变时不同种类的真菌间的作用关系可能发生转变并在环境因子的影响下在龋病的发生发展中产生正性或负性效应。本项目成果可为阐明口腔真菌组在口腔康稳态维持中的作用及其与儿童龋的关系，健全龋风险评估体系提供理论依据。