Functional signatures of oral dysbiosis during periodontitis progression revealed by microbial metatranscriptome analysis.
Functional signatures of oral dysbiosis during periodontitis progression revealed by microbial metatranscriptome analysis.
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DOI：
10.1186/s13073-015-0153-3
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发表时间：
2015
期刊：
影响因子：
12.3
通讯作者：
Frias-Lopez J
中科院分区：
文献类型：
--
作者：
Yost S;Duran-Pinedo AE;Teles R;Krishnan K;Frias-Lopez J
牙周炎是一种由多种微生物生物膜引起的炎症性疾病，影响全球7.43亿人。目前解释牙周炎进展的模型提出，口腔微生物组成员相对丰度的变化导致宿主-微生物组串扰的生态失调，然后导致炎症和骨丢失。使用宏基因组/元转录组组合分析的龈下微生物组在进展和非进展的网站，我们已经表征了牙周炎进展的不同的分子特征。对来自牙周炎患者的进展和稳定部位的龈下生物膜的样品进行元转录组分析。使用下一代测序（Illumina）获得全群落表达谱。使用“bowtie 2”针对构建的口腔微生物组数据库比对序列。使用在R软件包'NOISeqBio'上实现的非参数算法进行差异表达分析。我们总结了全球功能活动的口腔微生物群落的基因本体论（GO）的orthology的基础上的集合富集分析。基因本体富集分析表明，在基线的活性位点的术语相关的细胞运动，脂质A和肽聚糖的生物合成，铁，钾和氨基酸的运输的过度代表。牙周病病原体（Tannerella lasthia和牙龈卟啉单胞菌）上调不同的TonB依赖性受体、肽酶、蛋白酶、耐氧基因、铁转运基因、溶血素和CRISPR相关基因。令人惊讶的是，通常与该疾病无关的生物体（口腔链球菌、变形链球菌、中间链球菌、缓症链球菌、小韦荣球菌和荧光假单胞菌）高度活跃地转录推定的毒力因子。我们检测了与临床特征进展相关的活动模式。其中，我们发现钴胺素生物合成，蛋白水解和钾转运的表达谱与疾病的演变有关。我们确定了与生态失调的初始阶段相关的微生物群落的代谢变化。无论社区的总体组成如何，某些代谢特征与疾病进展一致。我们的研究结果表明，整个社区，而不仅仅是少数口腔病原体，是导致疾病进展的毒力增加的原因。NCT 01489839，2011年12月6日。本文的在线版本（doi：10.1186/s13073-015-0153-3）包含补充材料，可供授权用户使用。
Periodontitis is a polymicrobial biofilm-induced inflammatory disease that affects 743 million people worldwide. The current model to explain periodontitis progression proposes that changes in the relative abundance of members of the oral microbiome lead to dysbiosis in the host-microbiome crosstalk and then to inflammation and bone loss. Using combined metagenome/metatranscriptome analysis of the subgingival microbiome in progressing and non-progressing sites, we have characterized the distinct molecular signatures of periodontitis progression. Metatranscriptome analysis was conducted on samples from subgingival biofilms from progressing and stable sites from periodontitis patients. Community-wide expression profiles were obtained using Next Generation Sequencing (Illumina). Sequences were aligned using ‘bowtie2’ against a constructed oral microbiome database. Differential expression analysis was performed using the non-parametric algorithm implemented on the R package ‘NOISeqBio’. We summarized global functional activities of the oral microbial community by set enrichment analysis based on the Gene Ontology (GO) orthology. Gene ontology enrichment analysis showed an over-representation in the baseline of active sites of terms related to cell motility, lipid A and peptidoglycan biosynthesis, and transport of iron, potassium, and amino acids. Periodontal pathogens (Tannerella forsythia and Porphyromonas gingivalis) upregulated different TonB-dependent receptors, peptidases, proteases, aerotolerance genes, iron transport genes, hemolysins, and CRISPR-associated genes. Surprisingly, organisms that have not been usually associated with the disease (Streptococcus oralis, Streptococcus mutans, Streptococcus intermedius, Streptococcus mitis, Veillonella parvula, and Pseudomonas fluorenscens) were highly active transcribing putative virulence factors. We detected patterns of activities associated with progression of clinical traits. Among those we found that the profiles of expression of cobalamin biosynthesis, proteolysis, and potassium transport were associated with the evolution towards disease. We identified metabolic changes in the microbial community associated with the initial stages of dysbiosis. Regardless of the overall composition of the community, certain metabolic signatures are consistent with disease progression. Our results suggest that the whole community, and not just a handful of oral pathogens, is responsible for an increase in virulence that leads to progression. NCT01489839, 6 December 2011. The online version of this article (doi:10.1186/s13073-015-0153-3) contains supplementary material, which is available to authorized users.
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影响因子：
11
作者：
Duran-Pinedo, Ana E.;Chen, Tsute;Frias-Lopez, Jorge
通讯作者：
Frias-Lopez, Jorge
影响因子：
56.9
作者：
Gill, Steven R.;Pop, Mihai;Nelson, Karen E.
通讯作者：
Nelson, Karen E.
DOI：
10.1038/ismej.2014.155
发表时间：
2015-03
期刊：
The ISME journal
影响因子：
--
作者：
通讯作者：
--
影响因子：
6.7
作者：
GOODSON, JM;TANNER, ACR;SOCRANSKY, SS
通讯作者：
SOCRANSKY, SS
影响因子：
11
作者：
Griffen, Ann L.;Beall, Clifford J.;Leys, Eugene J.
通讯作者：
Leys, Eugene J.