Abstract
BackgroundPeriodontitis 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.MethodsMetatranscriptome 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.ResultsGene 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.ConclusionsWe 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.Trial registrationNCT01489839, 6 December 2011.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-015-0153-3) contains supplementary material, which is available to authorized users.
Highlights
Periodontitis is a polymicrobial biofilm-induced inflammatory disease that affects 743 million people worldwide
What was more striking was the complete rearrangement at the metagenome level between the baselines of sites that did not progress versus sites that did progress (Figure 1C)
Normalized counts were analyzed using LEfSe with default parameters, to identify significant differences at species level between the microbial communities compared. (A) Comparison baseline samples from active sites vs. progressing samples from active sites. (B) Comparison baseline samples from stable sites vs. follow-up samples from stable sites. (C) Comparison baseline samples from active sites vs. baseline samples from stable sites
Summary
Periodontitis is a polymicrobial biofilm-induced inflammatory disease that affects 743 million people worldwide. Imbalances of the oral microbiota, referred to as microbial dysbiosis, lead to a series of different oral diseases These dysbiotic microbial communities exhibit synergistic interactions for enhanced protection from host defenses, nutrient acquisition, and persistence in an inflammatory environment [1,2]. Periodontal disease is the sixth most prevalent health condition in the world affecting 743 million people worldwide [3]. It occurs in moderate form in 30% to 50% of American adults and in severe form in 10% of the population and is responsible for half of all tooth loss in adults [4,5]. Recent studies have suggested that periodontal diseases can influence the risk for certain systemic conditions such as cardiovascular diseases, diabetes, respiratory diseases, and can affect reproductive outcomes [6,7]
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