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Although the composition of the oral human microbiome is now well studied, regulation of genes within oral microbial communities remains mostly uncharacterized. Current concepts of periodontal disease and caries highlight the importance of oral biofilms and their role as etiological agents of those diseases. Currently, there is increased interest in exploring and characterizing changes in the composition and gene-expression profiles of oral microbial communities. These efforts aim to identify changes in functional activities that could explain the transition from health to disease and the reason for the chronicity of those infections. It is now clear that the functions of distinct species within the subgingival microbiota are intimately intertwined with the rest of the microbial community. This point highlights the relevance of examining the expression profile of specific species within the subgingival microbiota in the case of periodontal disease or caries lesions, in the context of the other members of the biofilm in vivo. Metatranscriptomic analysis of the oral community is the starting point for identifying environmental signals that modulate the shift in metabolism of the community from commensal to dysbiotic. These studies give a snapshot of the expression patterns of microbial communities and also allow us to determine triggers to diseases. For example, in the case of caries, studies have unveiled a potential new pathway of sugar metabolism, namely the use of sorbitol as an additional source of carbon by Streptococcus mutans; and in the case of periodontal disease, high levels of extracellular potassium could be a signal of disease. Longitudinal studies are needed to identify the real markers of the initial stages of caries and periodontal disease. More information on the gene-expression profiles of the host, along with the patterns from the microbiome, will lead to a clearer understanding of the modulation of health and disease. This review presents a summary of these initial studies, which have opened the door to a new understanding of the dynamics of the oral community during the dysbiotic process in the oral cavity., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Oral bacterial biofilms are highly complex microbial communities with up to 700 different bacterial taxa. We report here the use of metatranscriptomic analysis to study patterns of community gene expression in a multispecies biofilm model composed of species found in healthy oral biofilms (Actinomyces naeslundii, Lactobacillus casei, Streptococcus mitis, Veillonella parvula, and Fusobacterium nucleatum) and the same biofilm plus the periodontopathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. The presence of the periodontopathogens altered patterns in gene expression, and data indicate that transcription of protein-encoding genes and small noncoding RNAs is stimulated. In the healthy biofilm hypothetical proteins, transporters and transcriptional regulators were upregulated while chaperones and cell division proteins were downregulated. However, when the pathogens were present, chaperones were highly upregulated, probably due to increased levels of stress. We also observed a significant upregulation of ABC transport systems and putative transposases. Changes in Clusters of Orthologous Groups functional categories as well as gene set enrichment analysis based on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed that in the absence of pathogens, only sets of proteins related to transport and secondary metabolism were upregulated, while in the presence of pathogens, proteins related to growth and division as well as a large portion of transcription factors were upregulated. Finally, we identified several small noncoding RNAs whose predicted targets were genes differentially expressed in the open reading frame libraries. These results show the importance of pathogens controlling gene expression of a healthy oral community and the usefulness of metatranscriptomic techniques to study gene expression profiles in complex microbial community models.

Dysbiosis, or the imbalance in the structural and/or functional properties of the microbiome, is at the origin of important infectious inflammatory diseases such as inflammatory bowel disease (IBD) and periodontal disease. Periodontitis is a polymicrobial inflammatory disease that affects a large proportion of the world's population and has been associated with a wide variety of systemic health conditions, such as diabetes, cardiovascular and respiratory diseases. Dysbiosis has been identified as a key element in the development of the disease. However, the precise mechanisms and environmental signals that lead to the initiation of dysbiosis in the human microbiome are largely unknown. In a series of previous in vivo studies using metatranscriptomic analysis of periodontitis and its progression we identified several functional signatures that were highly associated with the disease. Among them, potassium ion transport appeared to be key in the process of pathogenesis. To confirm its importance we performed a series of in vitro experiments, in which we demonstrated that potassium levels a increased the virulence of the oral community as a whole and at the same time altering the immune response of gingival epithelium, increasing the production of TNF-α and reducing the expression of IL-6 and the antimicrobial peptide human β-defensin 3 (hBD-3). These results indicate that levels of potassium in the periodontal pocket could be an important element in of dysbiosis in the oral microbiome. They are a starting point for the identification of key environmental signals that modify the behavior of the oral microbiome from a symbiotic community to a dysbiotic one. [ABSTRACT FROM AUTHOR]