Beyond microbial community composition: functional activities of the oral microbiome in health and disease

The oral microbiome plays a relevant role in the health status of the host and is a key element in a variety of oral and non-oral diseases. Despite advances in our knowledge of changes in microbial composition associated with different health conditions the functional aspects of the oral microbiome that lead to dysbiosis remain for the most part unknown. In this review, we discuss the progress made towards understanding the functional role of the oral microbiome in health and disease and how novel technologies are expanding our knowledge on this subject.     

Interkingdom networking within the oral microbiome

Different sites within the oropharynx harbour unique microbial communities. Co-evolution of microbes and host has resulted in complex interkingdom circuitries. Metabolic signalling is crucial to these processes, and novel microbial communication factors are progressively being discovered. Resolving interkingdom networks will lead to better understanding of oral health or disease aetiology.     

Beyond the Venn diagram: the hunt for a core microbiome

Discovering a core microbiome is important for understanding the stable, consistent components across complex microbial assemblages. A core is typically defined as the suite of members shared among microbial consortia from similar habitats, and is represented by the overlapping areas of circles in Venn diagrams, in which each circle contains the membership of the sample or habitats being compared. Ecological insight into core microbiomes can be enriched by 'omics approaches that assess gene expression, thereby extending the concept of the core beyond taxonomically defined membership to community function and behaviour. Parameters defined by traditional ecology theory, such as composition, phylogeny, persistence and connectivity, will also create a more complex portrait of the core microbiome and advance understanding of the role of key microorganisms and functions within and across ecosystems.     

Cervicovaginal microbiome dynamics after taking oral probiotics

The vaginal microbiota is less complex than the gut microbiota, and the colonization of Lactobacillus in the female vagina is considered to be critical for reproductive health. Oral probiotics have been suggested as promising means to modulate vaginal homeostasis in the general population. In this study, 60 Chinese women were followed for over a year before, during, and after treatment with the probiotics Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14. Shotgun metagenomic data of 1334 samples from multiple body sites did not support a colonization route of the probiotics from the oral cavity to the intestinal tract and then to the vagina. Our analyses enable the classification of the cervicovaginal microbiome into a stable state and a state of dysbiosis. The microbiome in the stable group steadily maintained a relatively high abundance of Lactobacilli over one year, which was not affected by probiotic intake, whereas in the dysbiosis group, the microbiota was more diverse and changed markedly over time. Data from a subset of the dysbiosis group suggests this subgroup possibly benefited from supplementation with the probiotics,indicating that probiotics supplementation can be prescribed for women in a subclinical microbiome setting of dysbiosis, providing opportunities for targeted and personalized microbiome reconstitution.     

口腔微生物组与全身疾病的相关性

口腔是全身寄居微生物密度最高,种类最多的部位之一.口腔微生物不仅在龋病、牙周病、口腔癌等口腔疾病的病程中发挥重要作用,还与全身系统性疾病关系密切.口腔微生物组与全身系统性疾病之间存在紧密的相关性,可以促进全身系统性疾病的发生和发展.本文对口腔微生物组与全身系统性疾病的研究进展、口腔微生物组在全身系统疾病进程中的重要作用...     

Deep sequencing of the oral microbiome reveals signatures of periodontal disease

The oral microbiome, the complex ecosystem of microbes inhabiting the human mouth, harbors several thousands of bacterial types. The proliferation of pathogenic bacteria within the mouth gives rise to periodontitis, an inflammatory disease known to also constitute a risk factor for cardiovascular disease. While much is known about individual species associated with pathogenesis, the system-level mechanisms underlying the transition from health to disease are still poorly understood. Through the sequencing of the 16S rRNA gene and of whole community DNA we provide a glimpse at the global genetic, metabolic, and ecological changes associated with periodontitis in 15 subgingival plaque samples, four from each of two periodontitis patients, and the remaining samples from three healthy individuals. We also demonstrate the power of whole-metagenome sequencing approaches in characterizing the genomes of key players in the oral microbiome, including an unculturable TM7 organism. We reveal the disease microbiome to be enriched in virulence factors, and adapted to a parasitic lifestyle that takes advantage of the disrupted host homeostasis. Furthermore, diseased samples share a common structure that was not found in completely healthy samples, suggesting that the disease state may occupy a narrow region within the space of possible configurations of the oral microbiome. Our pilot study demonstrates the power of high-throughput sequencing as a tool for understanding the role of the oral microbiome in periodontal disease. Despite a modest level of sequencing (~2 lanes Illumina 76 bp PE) and high human DNA contamination (up to ~90%) we were able to partially reconstruct several oral microbes and to preliminarily characterize some systems-level differences between the healthy and diseased oral microbiomes.     

Defining the healthy "core microbiome" of oral microbial communities

Background  

Most studies examining the commensal human oral microbiome are focused on disease or are limited in methodology. In order to diagnose and treat diseases at an early and reversible stage an in-depth definition of health is indispensible. The aim of this study therefore was to define the healthy oral microbiome using recent advances in sequencing technology (454 pyrosequencing).     

Characterization of the rat oral microbiome and the effects of dietary nitrate

The nitrate–nitrite–NO pathway to nitric oxide (NO) production is a symbiotic pathway in mammals that is dependent on nitrate reducing oral commensal bacteria. Studies suggest that by contributing NO to the mammalian host, the oral microbiome helps maintain cardiovascular health. To begin to understand how changes in oral microbiota affect physiological functions such as blood pressure, we have characterized the Wistar rat nitrate reducing oral microbiome. Using 16S rRNA gene sequencing and analysis we compare the native Wistar rat tongue microbiome to that of healthy humans and to that of rats with sodium nitrate and chlorhexidine mouthwash treatments. We demonstrate that the rat tongue microbiome is less diverse than the human tongue microbiome, but that the physiological activity is comparable, as sodium nitrate supplementation significantly lowered diastolic blood pressure in Wistar rats and also lowers blood pressure (diastolic and systolic) in humans. We also show for the first time that sodium nitrate supplementation alters the abundance of specific bacterial species on the tongue. Our results suggest that the changes in oral nitrate reducing bacteria may affect nitric oxide availability and physiological functions such as blood pressure. Understanding individual changes in human oral microbiome may offer novel dietary approaches to restore NO availability and blood pressure.     

人类口腔微生物组学研究:现状、挑战及机遇

全球超过一半的人口患有口腔疾病,其医护费用与全球十大常见死亡病因的花费相当,而且口腔感染与早产、动脉粥样硬化、肝硬化、糖尿病、阿尔茨海默病等全身性或慢性疾病显著相关,因此,口腔微生物组一直是人类微生物组计划的主要研究对象之一。与人体其他部位比较,口腔微生物组研究具有取样快捷、宿主反应表征方便、干预手段直接有效等特点;同时,超过65%的口腔细菌类群已可培养,诸多代表性菌株的全基因组信息已破译。因此口腔微生物组在菌群内部调控网络及其与宿主互作机制、局部感染对远隔器官的影响机制、以及基于菌群的慢病早期预警等微生物组研究核心科学问题上具备作为模式研究体系与技术示范对象的重要优势。本文在分析口腔微生物组学国际、国内研究现状的基础上,建议尽快启动中国人口腔微生物组计划(China human oral microbiome project,CHOMP),通过产学研协同攻关,开拓基于口腔菌群的口腔及全身系统性疾病的个体化预防、诊断及治疗策略。     

The oral microbiome of pregnant women facilitates gestational diabetes discrimination

The oral microbiota plays an important role in the development of various diseases,whereas its association with gestational diabetes mellitus (GDM) remains largely unclear.The aim of this study is to identify biomarkers from the oral microbiota of GDM patients by analyzing the microbiome of the saliva and dental plaque samples of 111 pregnant women.We find that the microbiota of both types of oral samples in GDM patients exhibits differences and significantly varies from that of patients with periodontitis or dental caries.Using bacterial biomarkers from the oral microbiota,GDM classification models based on support vector machine and random forest algorithms are constructed.The area under curve (AUC) value of the classification model constructed by combination of Lautropia and Neisseria in dental plaque and Streptococcus in saliva reaches 0.83,and the value achieves a maximum value of 0.89 by adding clinical features.These findings suggest that certain bacteria in either saliva or dental plaque can effectively distinguish women with GDM from healthy pregnant women,which provides evidence of oral microbiome as an informative source for developing noninvasive biomarkers of GDM.     

CORE: a phylogenetically-curated 16S rDNA database of the core oral microbiome

Comparing bacterial 16S rDNA sequences to GenBank and other large public databases via BLAST often provides results of little use for identification and taxonomic assignment of the organisms of interest. The human microbiome, and in particular the oral microbiome, includes many taxa, and accurate identification of sequence data is essential for studies of these communities. For this purpose, a phylogenetically curated 16S rDNA database of the core oral microbiome, CORE, was developed. The goal was to include a comprehensive and minimally redundant representation of the bacteria that regularly reside in the human oral cavity with computationally robust classification at the level of species and genus. Clades of cultivated and uncultivated taxa were formed based on sequence analyses using multiple criteria, including maximum-likelihood-based topology and bootstrap support, genetic distance, and previous naming. A number of classification inconsistencies for previously named species, especially at the level of genus, were resolved. The performance of the CORE database for identifying clinical sequences was compared to that of three publicly available databases, GenBank nr/nt, RDP and HOMD, using a set of sequencing reads that had not been used in creation of the database. CORE offered improved performance compared to other public databases for identification of human oral bacterial 16S sequences by a number of criteria. In addition, the CORE database and phylogenetic tree provide a framework for measures of community divergence, and the focused size of the database offers advantages of efficiency for BLAST searching of large datasets. The CORE database is available as a searchable interface and for download at http://microbiome.osu.edu.     

A potential oral microbiome signature associated with coronary artery disease in Tunisia

The coronary artery disease (CAD) is a chronic inflammatory disease involving genetic as well as environmental factors. Recent evidence suggests that the oral microbiome has a significant role in triggering atherosclerosis. The present study assessed the oral microbiome composition variation between coronary patients and healthy subjects in order to identify a potential pathogenic signature associated with CAD. We performed metagenomic profiling of salivary microbiomes by 16S ribosomal RNA (rRNA) next-generation sequencing. Oral microbiota profiling was performed for 30 individuals including 20 patients with CAD and ten healthy individuals without carotid plaques or previous stroke or myocardial infarction.We found that oral microbial communities in patients and healthy controls are represented by similar global core oral microbiome. The predominant taxa belonged to Firmicutes (genus Streptococcus, Veillonella, Granulicatella, Selenomonas), Proteobacteria (genus Neisseria, Haemophilus), Actinobacteria (genus Rothia), Bacteroidetes (genus Prevotella, Porphyromonas), and Fusobacteria (genus Fusobacterium, Leptotrichia). More than 60% relative abundance of each sample for both CAD patients and controls is represented by three major genera including Streptococcus (24.97 and 26.33%), Veillonella (21.43 and 19.91%), and Neisseria (14.23 and 15.33%).Using penalized regression analysis, the bacterial genus Eikenella was involved as the major discriminant genus for both status and Syntax score of CAD. We also reported a significant negative correlation between Syntax score and Eikenella abundance in coronary patients’ group (Spearman rho = −0.68, P=0.00094).In conclusion, the abundance of Eikenella in oral coronary patient samples compared with controls could be a prominent pathological indicator for the development of CAD.     

Dysbiosis of salivary microbiome and cytokines influence oral squamous cell carcinoma through inflammation

Archives of Microbiology - Advanced combinatorial treatments of surgery, chemotherapy, and radiotherapy do not have any effect on the enhancement of a 5-year survival rate of oral squamous cell...