Applied Oral Sciences & Community Dental Care, Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China.
Department of Stomatology, Beijing Friendship Hospital, Capital Medical University, Xicheng District, Beijing, China; Dental Public Health, Faculty of Dentistry, The University of Hong Kong, Hong Kong, China.
J Dent. 2024 Jul;146:105018. doi: 10.1016/j.jdent.2024.105018. Epub 2024 Apr 27.
This study aimed to identify the oral microbiota factors contributing to low birth weight (LBW) in Chinese pregnant women and develop a prediction model using machine learning.
A nested case-control study was conducted in a prospective cohort of 580 Chinese pregnant women, with 23 LBW cases and 23 healthy delivery controls matched for age and smoking habit. Saliva samples were collected at early and late pregnancy, and microbiome profiles were analyzed through 16S rRNA gene sequencing.
The relative abundance of Streptococcus was over-represented (median 0.259 vs. 0.116) and Saccharibacteria_TM7 was under-represented (median 0.033 vs. 0.068) in the LBW case group than in controls (p < 0.001, p = 0.015 respectively). Ten species were identified as microbiome biomarkers of LBW by LEfSe analysis, which included 7 species within the genus of Streptococcus or as part of 'nutritionally variant streptococci' (NVS), 2 species of opportunistic pathogen Leptotrichia buccalis and Gemella sanguinis (all LDA score>3.5) as risk biomarkers, and one species of Saccharibacteria TM7 as a beneficial biomarker (LDA= -4.5). The machine-learning model based on these 10 distinguished oral microbiota species could predict LBW, with an accuracy of 82 %, sensitivity of 91 %, and specificity of 73 % (AUC-ROC score 0.89, 95 % CI: 0.75-1.0). Results of α-diversity showed that mothers who delivered LBW infants had less stable salivary microbiota construction throughout pregnancy than the control group (measured by Shannon, p = 0.048; and Pielou's, p = 0.021), however the microbiome diversity did not improve the prediction accuracy of LBW.
A machine-learning oral microbiome model shows promise in predicting low-birth-weight delivery. Even in cases where oral health is not significantly compromised, opportunistic pathogens or rarer taxa associated with adverse pregnancy outcomes can still be identified in the oral cavity.
This study highlights the potential complexity of the relationship between oral microbiome and pregnancy outcomes, indicating that mechanisms underlying the association between oral microbiota and adverse pregnancy outcomes may involve complex interactions between host factors, microbiota, and systemic conditions. Using machine learning to develop a predictive model based on specific oral microbiota biomarkers provides a potential for personalized medicine approaches. Future prediction models should incorporate clinical metadata to be clinically useful for improving maternal and child health.
本研究旨在识别导致中国孕妇低出生体重(LBW)的口腔微生物因素,并利用机器学习建立预测模型。
采用前瞻性队列研究,对 580 名中国孕妇进行了嵌套病例对照研究,其中 23 例 LBW 病例和 23 例健康分娩对照按年龄和吸烟习惯匹配。在妊娠早期和晚期采集唾液样本,并通过 16S rRNA 基因测序分析微生物组谱。
与对照组相比,LBW 病例组链球菌属的相对丰度较高(中位数 0.259 比 0.116),而 Saccharibacteria_TM7 的相对丰度较低(中位数 0.033 比 0.068)(p<0.001,p=0.015)。LEfSe 分析鉴定出 10 种微生物组生物标志物与 LBW 相关,其中包括 7 种链球菌属或属于“营养变异链球菌”(NVS)的物种,2 种机会性病原体 Leptotrichia buccalis 和 Gemella sanguinis(所有 LDA 评分>3.5)作为风险生物标志物,以及 1 种 Saccharibacteria TM7 作为有益生物标志物(LDA=-4.5)。基于这 10 种有区别的口腔微生物物种的机器学习模型可以预测 LBW,其准确性为 82%,灵敏度为 91%,特异性为 73%(AUC-ROC 评分 0.89,95%CI:0.75-1.0)。α多样性结果表明,与对照组相比,分娩 LBW 婴儿的母亲在整个孕期唾液微生物组的构建稳定性较差(用 Shannon 衡量,p=0.048;用 Pielou 衡量,p=0.021),然而微生物组多样性并不能提高 LBW 的预测准确性。
基于机器学习的口腔微生物组模型在预测低出生体重分娩方面有一定的前景。即使口腔健康没有明显受损,与不良妊娠结局相关的机会性病原体或更罕见的分类群仍可在口腔中被识别。
本研究强调了口腔微生物组与妊娠结局之间关系的潜在复杂性,表明口腔微生物组与不良妊娠结局之间的关联机制可能涉及宿主因素、微生物组和全身状况之间的复杂相互作用。利用机器学习基于特定的口腔微生物组生物标志物建立预测模型为个性化医疗方法提供了一种可能。未来的预测模型应纳入临床元数据,以提高母婴健康的临床实用性。