DOMHaIN Longitudinal Oral Microbiome

The oral microbiome comprises distinct microbial communities that colonize diverse ecological niches across the oral cavity, the composition of which are influenced by nutrient and substrate availability, host genetics, diet, behavior, age, and other diverse host and environmental factors. Unlike other densely populated human-associated microbial ecosystems (e.g., gut, urogenital), the oral microbiome is regularly and directly exposed to the external environment and is therefore likely less stable over time. Cross sectional studies of the oral microbiome capture a glimpse of this temporal dynamism, yet a full appreciation of the relative stability, robusticity, and spatial structure of the oral environment is necessary to understand the role of microbial communities in promoting health or disease. Here we investigate the spatial and temporal stability of the oral microbiome over three sampling time points in the context of HIV infection and exposure. Individual teeth were sampled from a cohort of 565 Nigerian children with varying levels of tooth decay severity (i.e., caries disease). We collected 1,960 supragingival plaque samples and characterized the oral microbiome using a metataxonomic approach targeting an approximately 478 bp region of the bacterial rpoC gene. We found that both infection and exposure to HIV have significant effects on the stability of the supragingival plaque microbiome at both the spatial and temporal scale. Specifically, we detect (1) significantly lower taxonomic turnover of the oral community among exposed and infected children compared to unexposed children, (2) we find that HIV infection homogenizes the oral community across the anterior and posterior dentition, and (3) that impaired immunity (i.e., low CD4 count) and low taxonomic turnover over time in children living with HIV is associated with higher frequency of cariogenic taxa including Streptococcus mutans. Our results document substantial community fluctuations over time in children unexposed to HIV independent of oral health status. This suggests that the oral community, under typical conditions, rapidly adapts to environmental perturbations to maintain homeostasis and that long-term taxonomic rigidity is a signal of community dysfunction, potentially leading to a higher incidence of oral disease including caries.

口腔微生物组（oral microbiome）由定植于口腔内不同生态位的独特微生物群落组成，其组成受营养物质与底物可获得性、宿主遗传学、饮食、行为习惯、年龄以及其他多种宿主与环境因素的影响。与其他与人共生的高密度微生物生态系统（如肠道、泌尿生殖系统）不同，口腔微生物组会频繁直接暴露于外部环境，因此其随时间的稳定性相对更差。针对口腔微生物组的横断面研究仅能窥见其时间动态性的一隅，但若要全面理解口腔环境的相对稳定性、鲁棒性与空间结构，进而阐明微生物群落对健康维持或疾病发生的作用，则需开展更系统的研究。
本研究针对HIV感染与暴露情境，于三个采样时间点探究口腔微生物组的空间与时间稳定性。研究对象为565名尼日利亚儿童组成的队列，我们从其个体牙齿上采集样本，这些儿童的龋齿（caries disease）严重程度各不相同。本研究共收集1960份龈上菌斑（supragingival plaque）样本，并采用靶向细菌rpoC基因约478bp区域的宏分类组学（metataxonomic）方法对口腔微生物组进行特征分析。研究发现，HIV感染与暴露均会在空间与时间尺度上对龈上菌斑微生物组的稳定性产生显著影响。具体而言，我们检测到以下结果：（1）与未暴露儿童相比，暴露及感染HIV的儿童其口腔群落的分类学更替率显著更低；（2）HIV感染会使口腔群落在前牙列与后牙列间趋于同质化；（3）HIV感染者的免疫功能受损（即CD4细胞计数偏低）以及随时间推移出现的低分类学更替率，与包括变形链球菌（Streptococcus mutans）在内的致龋类群（cariogenic taxa）的高检出频率显著相关。
本研究结果显示，未暴露于HIV的儿童，其口腔群落随时间会出现显著的群落波动，且这一现象与口腔健康状况无关。这表明，在正常生理条件下，口腔群落会快速响应环境扰动以维持稳态；而长期的分类学刚性则是群落功能失调的信号，可能会提升包括龋齿在内的口腔疾病的发病风险。