Hyposalivation and the Human Oral Microbiome

描述(由申请人提供)：唾液流率异常低，是与冠面和根面龋齿相关的主要健康问题，尽管临床实践最好，但严重降低了生活质量。药物是慢性肺功能减退的最常见原因。慢性肺功能减退的第二个主要原因是干燥综合征，这是发达国家最常见的自身免疫性疾病之一。裸露牙面的微生物区系在龋病形成中起着关键作用。为了减少这些人群的龋齿负担和牙齿缺失，我们建议确定与急性和慢性营养不良以及随后的龋病发展相关的微生物区系组成的变化。检测微生物区系的早期诊断变化将有助于早期治疗干预。虽然许多以培养为基础的研究已经研究了牙列不良对口腔微生物群落的影响，但还没有人研究随着时间的推移在不同的牙龈上位置的空间上的明显影响。此外，培养提供了细菌多样性和群落结构的有限视角。我们初步的、基于测序的数据显示，在没有牙合不足的情况下，牙龈上菌斑的分类组成在不同的牙齿之间和不同的牙齿之间存在差异。这一发现，再加上龋齿的分布以一种特定的方式向门牙和尖牙转移的观察表明，如果我们要理解(并最终防止)从与健康相关的社区状态向与龋齿相关的社区状态的进展，我们需要在没有和存在牙龈上社区的情况下检查时空变化。本申请通过定义和描述在多个空间和时间尺度上的牙龈上微生物群落在健康和急性和慢性营养不良状态下的种群水平的转变和差异来满足这一需求。目的1：研究健康成人在无牙合不良的情况下，牙龈上和唾液微生物区系的时空动态特征。目的2：描述药物引起的牙周炎对健康成人牙龈上和唾液微生物区系的急性影响。目的：评价慢性淋巴功能减退对干燥综合征患者牙龈上和唾液微生物区系的影响。我们的长期目标是为低活度相关的致龋性微生物群落开发新的诊断标记物，以及开发基于生态的新疗法来降低高危患者的龋齿发生率，并更好地了解微生物群落在龋病发生中的作用。

DESCRIPTION (provided by applicant): Hyposalivation, or an abnormally low salivary flow rate, is a major health problem associated with coronal and root surface dental caries, and a profound reduction in quality of life despite best clinical practices. Medications are the most common cause of chronic hyposalivation. A second major cause of chronic hyposalivation is Sj¿gren's Syndrome, one of the most prevalent autoimmune disorders in the developed world. The microbiota of the exposed tooth surface plays a critical role in caries formation. In order to reduce the burden of caries and tooth loss in these populations, we propose to identify shifts in the composition of the microbiota that are associated with the acute and chronic states of hyposalivation and the subsequent development of caries. Detection of early diagnostic changes in the microbiota will facilitate early therapeutic intervention. Although many culture-based studies have examined the impact of hyposalivation on oral microbial communities, none have examined spatially explicit impacts at distinct supragingival sites over time. Furthermore, cultivation provides a limited view of bacterial diversity and community structure. Our preliminary, sequencing-based data show that the taxonomic composition of supragingival plaques varies between and across teeth in the absence of hyposalivation. This finding, combined with the observation that the distribution of caries shifts in a site-specific manner to the incisors and canines in states of hyposalivation, suggests that we need to examine spatiotemporal variation in supragingival communities in the absence and presence of hyposalivation if we are to understand (and ultimately prevent) the progression from health- associated to hyposalivation- and caries-associated community states. This Application addresses this need by defining and characterizing population-level transitions and differences in supragingival microbial communities at multiple spatial and temporal scales in health and in acute and chronic states of hyposalivation. Aim 1: Characterize the spatiotemporal dynamics of the supragingival and salivary microbiota in healthy adults in the absence of hyposalivation. Aim 2: Characterize acute impacts of medication-induced hyposalivation on the supragingival and salivary microbiota of healthy adults. Aim 3: Evaluate impact of chronic hyposalivation on the supragingival and salivary microbiota in patients with Sj¿gren's Syndrome. Our long-term objectives are to develop new diagnostic markers for hyposalivation-associated cariogenic microbial communities, as well as to develop novel ecologically-based therapeutics to decrease dental caries incidence in high risk patients, and to understand better the role of microbial communities in cariogenesis.