Department of Periodontology and Operative Dentistry, Muenster University Hospital, Albert-Schweitzer-Campus 1, Building W30, Münster, 48149, Germany.
Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.
Microbiome. 2024 Oct 26;12(1):220. doi: 10.1186/s40168-024-01945-3.
Periodontitis, a prevalent chronic inflammatory disease, offers insights into the broader landscape of chronic inflammatory conditions. The progression and treatment outcomes of periodontitis are closely related to the oral microbiota's composition. Adjunctive systemic Amoxicillin 500 mg and Metronidazole 400 mg, often prescribed thrice daily for 7 days to enhance periodontal therapy's efficacy, have lasting effects on the oral microbiome. However, the precise mechanism through which the oral microbiome influences clinical outcomes in periodontitis patients remains debated. This investigation explores the pivotal role of the oral microbiome's composition in mediating the outcomes of adjunctive systemic antibiotic treatment.
Subgingival plaque samples from 10 periodontally healthy and 163 periodontitis patients from a randomized clinical trial on periodontal therapy were analyzed. Patients received either adjunctive amoxicillin/metronidazole or a placebo after mechanical periodontal treatment. Microbial samples were collected at various intervals up to 26 months post-therapy. Using topic models, we identified microbial communities associated with normobiotic and dysbiotic states, validated with 86 external and 40 internal samples. Logistic regression models evaluated the association between these microbial communities and clinical periodontitis parameters. A Directed Acyclic Graph (DAG) determined the mediating role of oral microbiota in the causal path of antibiotic treatment effects on clinical outcomes.
We identified clear distinctions between dysbiotic and normobiotic microbial communities, differentiating healthy from periodontitis subjects. Dysbiotic states consistently associated with below median %Pocket Probing Depth ≥ 5 mm (OR = 1.26, 95% CI [1.14-1.42]) and %Bleeding on Probing (OR = 1.09, 95% CI [1.00-1.18]). Factors like microbial response to treatment, smoking, and age were predictors of clinical attachment loss progression, whereas sex and antibiotic treatment were not. Further, we showed that the oral microbial treatment response plays a crucial role in the causal effect of antibiotic treatment on clinical treatment outcomes.
The shift towards a normobiotic subgingival microbiome, primarily induced by adjunctive antibiotics, underscores the potential for microbiome-targeted interventions to enhance therapeutic efficacy in chronic inflammatory conditions. This study reaffirms the importance of understanding the oral microbiome's role in periodontal health and paves the way for future research exploring personalized treatment strategies based on individual microbiome profiles. Video Abstract.
牙周炎是一种普遍的慢性炎症性疾病，它为我们了解更广泛的慢性炎症性疾病提供了线索。牙周炎的进展和治疗结果与口腔微生物群的组成密切相关。辅助全身使用阿莫西林 500 毫克和甲硝唑 400 毫克，通常每天三次，持续 7 天，以增强牙周治疗的疗效，对口腔微生物组有持久的影响。然而，口腔微生物组如何影响牙周炎患者的临床结果的具体机制仍存在争议。本研究探讨了口腔微生物组组成在调节辅助全身抗生素治疗结果中的关键作用。
对一项牙周病治疗的随机临床试验中 10 名牙周健康和 163 名牙周炎患者的龈下菌斑样本进行了分析。患者在机械牙周治疗后接受辅助阿莫西林/甲硝唑或安慰剂治疗。在治疗后长达 26 个月的时间内，采集了不同时间的微生物样本。我们使用主题模型识别与正常生物和失调状态相关的微生物群落，并使用 86 个外部样本和 40 个内部样本进行验证。逻辑回归模型评估了这些微生物群落与临床牙周炎参数之间的关联。有向无环图（DAG）确定了口腔微生物在抗生素治疗对临床结果的因果路径中中介作用。
我们发现，在健康受试者和牙周炎患者之间，失调和正常生物的微生物群落之间存在明显的差异。失调状态与低于中位数的%探诊深度≥5 毫米（OR=1.26，95%CI[1.14-1.42]）和%探诊出血（OR=1.09，95%CI[1.00-1.18]）持续相关。微生物对治疗的反应、吸烟和年龄等因素是临床附着丧失进展的预测因素，而性别和抗生素治疗则不是。此外，我们表明，口腔微生物治疗反应在抗生素治疗对临床治疗结果的因果效应中起着至关重要的作用。
向正常龈下微生物组的转变，主要是由辅助抗生素引起的，这突显了针对微生物组的干预措施有可能增强慢性炎症性疾病的治疗效果。本研究重申了了解口腔微生物组在牙周健康中的作用的重要性，并为未来探索基于个体微生物组谱的个性化治疗策略铺平了道路。
