The role of the oral microbiota in the causal effect of adjunctive antibiotics on clinical outcomes in stage III-IV periodontitis patients.

IF 13.8 1区 生物学 Q1 MICROBIOLOGY
Sven Kleine Bardenhorst, Daniel Hagenfeld, Johannes Matern, Karola Prior, Inga Harks, Peter Eickholz, Katrin Lorenz, Ti-Sun Kim, Thomas Kocher, Jörg Meyle, Doğan Kaner, Yvonne Jockel-Schneider, Dag Harmsen, Benjamin Ehmke
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引用次数: 0

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

口腔微生物群在辅助抗生素对 III-IV 期牙周炎患者临床疗效的因果效应中的作用。
背景:牙周炎是一种普遍存在的慢性炎症性疾病,它使人们对更广泛的慢性炎症性疾病有了更深入的了解。牙周炎的进展和治疗效果与口腔微生物群的组成密切相关。阿莫西林 500 毫克和甲硝唑 400 毫克是辅助性全身用药,通常每天三次,连用 7 天,以提高牙周治疗的疗效,对口腔微生物群有持久的影响。然而,口腔微生物组影响牙周炎患者临床疗效的确切机制仍存在争议。本研究探讨了口腔微生物组的组成在调节系统性抗生素辅助治疗效果中的关键作用:方法:分析了一项牙周治疗随机临床试验中 10 名牙周健康患者和 163 名牙周炎患者的龈下菌斑样本。患者在接受机械性牙周治疗后,接受阿莫西林/甲硝唑或安慰剂的辅助治疗。在治疗后 26 个月内的不同时间间隔收集微生物样本。通过使用主题模型,我们确定了与正常生物状态和菌群失调状态相关的微生物群落,并对 86 份外部样本和 40 份内部样本进行了验证。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)确定了口腔微生物群在抗生素治疗对临床结果影响的因果关系中的中介作用:我们发现了菌群失调与正常生物微生物群落之间的明显区别,并将健康人与牙周炎患者区分开来。菌群失调状态与低于中位数的%牙槽探诊深度≥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])密切相关。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,我们还发现,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:结论:龈下微生物群向正常生物群的转变主要是由辅助抗生素引起的,这凸显了以微生物群为目标的干预措施在提高慢性炎症治疗效果方面的潜力。这项研究再次证实了了解口腔微生物组在牙周健康中的作用的重要性,并为未来研究探索基于个体微生物组特征的个性化治疗策略铺平了道路。视频摘要。
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来源期刊
Microbiome
Microbiome MICROBIOLOGY-
CiteScore
21.90
自引率
2.60%
发文量
198
审稿时长
4 weeks
期刊介绍: Microbiome is a journal that focuses on studies of microbiomes in humans, animals, plants, and the environment. It covers both natural and manipulated microbiomes, such as those in agriculture. The journal is interested in research that uses meta-omics approaches or novel bioinformatics tools and emphasizes the community/host interaction and structure-function relationship within the microbiome. Studies that go beyond descriptive omics surveys and include experimental or theoretical approaches will be considered for publication. The journal also encourages research that establishes cause and effect relationships and supports proposed microbiome functions. However, studies of individual microbial isolates/species without exploring their impact on the host or the complex microbiome structures and functions will not be considered for publication. Microbiome is indexed in BIOSIS, Current Contents, DOAJ, Embase, MEDLINE, PubMed, PubMed Central, and Science Citations Index Expanded.
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