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牙周袋微生物群落治疗前后的多组学分析

Multi-omics Analysis of Periodontal Pocket Microbial Communities Pre- and Posttreatment.

作者信息

Califf Katy J, Schwarzberg-Lipson Karen, Garg Neha, Gibbons Sean M, Caporaso J Gregory, Slots Jørgen, Cohen Chloe, Dorrestein Pieter C, Kelley Scott T

机构信息

Center for Microbial Genetics and Genomics and Department of Biological Sciences, Northern Arizona University, Flagstaff, Arizona, USA.

Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, California, USA.

出版信息

mSystems. 2017 Jun 20;2(3). doi: 10.1128/mSystems.00016-17. eCollection 2017 May-Jun.

Abstract

Periodontitis is a polymicrobial infectious disease that causes breakdown of the periodontal ligament and alveolar bone. We employed a meta-omics approach that included microbial 16S rRNA amplicon sequencing, shotgun metagenomics, and tandem mass spectrometry to analyze sub- and supragingival biofilms in adults with chronic periodontitis pre- and posttreatment with 0.25% sodium hypochlorite. Microbial samples were collected with periodontal curettes from 3- to 12-mm-deep periodontal pockets at the baseline and at 2 weeks and 3 months. All data types showed high interpersonal variability, and there was a significant correlation between phylogenetic diversity and pocket depth at the baseline and a strong correlation (rho = 0.21; = 0.008) between metabolite diversity and maximum pocket depth (MPD). Analysis of subgingival baseline samples (16S rRNA and shotgun metagenomics) found positive correlations between abundances of particular bacterial genera and MPD, including , , , and species and unknown taxon SHD-231. At 2 weeks posttreatment, we observed an almost complete turnover in the bacterial genera (16S rRNA) and species (shotgun metagenomics) correlated with MPD. Among the metabolites detected, the medians of the 20 most abundant metabolites were significantly correlated with MPD pre- and posttreatment. Finally, tests of periodontal biofilm community instability found markedly higher taxonomic instability in patients who did not improve posttreatment than in patients who did improve (UniFrac distances; = -3.59; = 0.002). Interestingly, the opposite pattern occurred in the metabolic profiles (Bray-Curtis; = 2.42; = 0.02). Our results suggested that multi-omics approaches, and metabolomics analysis in particular, could enhance treatment prediction and reveal patients most likely to improve posttreatment. Periodontal disease affects the majority of adults worldwide and has been linked to numerous systemic diseases. Despite decades of research, the reasons for the substantial differences among periodontitis patients in disease incidence, progressivity, and response to treatment remain poorly understood. While deep sequencing of oral bacterial communities has greatly expanded our comprehension of the microbial diversity of periodontal disease and identified associations with healthy and disease states, predicting treatment outcomes remains elusive. Our results suggest that combining multiple omics approaches enhances the ability to differentiate among disease states and determine differential effects of treatment, particularly with the addition of metabolomic information. Furthermore, multi-omics analysis of biofilm community instability indicated that these approaches provide new tools for investigating the ecological dynamics underlying the progressive periodontal disease process.

摘要

牙周炎是一种多微生物感染性疾病,会导致牙周韧带和牙槽骨破坏。我们采用了一种多组学方法,包括微生物16S rRNA扩增子测序、鸟枪法宏基因组学和串联质谱,来分析慢性牙周炎成人患者在使用0.25%次氯酸钠治疗前后的龈下和龈上生物膜。在基线、2周和3个月时,用牙周刮匙从深度为3至12毫米的牙周袋中采集微生物样本。所有数据类型均显示出较高的个体间变异性,在基线时系统发育多样性与牙周袋深度之间存在显著相关性,代谢物多样性与最大牙周袋深度(MPD)之间存在强相关性(rho = 0.21;P = 0.008)。对龈下基线样本(16S rRNA和鸟枪法宏基因组学)的分析发现,特定细菌属的丰度与MPD之间存在正相关,包括 、 、 和 种以及未知分类单元SHD - 231。在治疗后2周,我们观察到与MPD相关的细菌属(16S rRNA)和物种(鸟枪法宏基因组学)几乎完全更替。在检测到的代谢物中,20种最丰富代谢物的中位数在治疗前后均与MPD显著相关。最后,对牙周生物膜群落不稳定性的测试发现,治疗后未改善的患者的分类学不稳定性明显高于改善的患者(UniFrac距离;P = -3.59;P = 0.002)。有趣的是,代谢谱中出现了相反的模式(Bray - Curtis;P = 2.42;P = 0.02)。我们的结果表明,多组学方法,尤其是代谢组学分析,可以增强治疗预测能力,并揭示最有可能在治疗后改善的患者。牙周疾病影响着全球大多数成年人,并与多种全身性疾病有关。尽管经过了数十年的研究,但牙周炎患者在疾病发病率、进展性和对治疗的反应方面存在巨大差异的原因仍知之甚少。虽然对口腔细菌群落的深度测序极大地扩展了我们对牙周疾病微生物多样性的理解,并确定了与健康和疾病状态的关联,但预测治疗结果仍然难以实现。我们的结果表明,结合多种组学方法可以增强区分疾病状态和确定治疗差异效应的能力,特别是加上代谢组学信息。此外,对生物膜群落不稳定性的多组学分析表明,这些方法为研究牙周疾病进展过程背后的生态动力学提供了新工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dbc/5513737/d3a96fba4715/sys0031721120001.jpg

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