The oralome and its dysbiosis: New insights into oral microbiome-host interactions

Abstract

The oralome is the summary of the dynamic interactions orchestrated between the ecological community of oral microorganisms (comprised of up to approximately 1000 species of bacteria, fungi, viruses, archaea and protozoa - the oral microbiome) that live in the oral cavity and the host. These microorganisms form a complex ecosystem that thrive in the dynamic oral environment in a symbiotic relationship with the human host. However, the microbial composition is significantly affected by interspecies and host-microbial interactions, which in turn, can impact the health and disease status of the host. In this review, we discuss the composition of the oralome and inter-species and host-microbial interactions that take place in the oral cavity and examine how these interactions change from healthy (eubiotic) to disease (dysbiotic) states. We further discuss the dysbiotic signatures associated with periodontitis and caries and their sequalae, (e.g., tooth/bone loss and pulpitis), and the systemic diseases associated with these oral diseases, such as infective endocarditis, atherosclerosis, diabetes, Alzheimer's disease and head and neck/oral cancer. We then discuss current computational techniques to assess dysbiotic oral microbiome changes. Lastly, we discuss current and novel techniques for modulation of the dysbiotic oral microbiome that may help in disease prevention and treatment, including standard hygiene methods, prebiotics, probiotics, use of nano-sized drug delivery systems (nano-DDS), extracellular polymeric matrix (EPM) disruption, and host response modulators.

Keywords: Complex diseases; Dysbiosis; Host-microbe interactions; Oral biofilm; Oral microbiome.

Graphical abstract

Fig. 1

Interactions between microorganisms that may drive the community assembly of oral biofilms. Different interactions are designated as having a primary function in synergy, signaling or antagonism. However, in many cases, components may have multiple roles with both positive and negative impacts depending on the situation. Reprinted from Jakubovics .

Fig. 2

Oral biofilm dysbiotic signature leading to dental caries.

Fig. 3

Main hypotheses proposed so far for the initiation of periodontitis.

Fig. 4

Oral microbial dysbiosis is associated with oral cancer development through different mechanisms. A - Oral infections and dysbiosis are responsible for promoting a pro-inflammatory microenvironment, wherein inflammatory cytokines and matrix metalloproteinases favor the development and progression of tumors. Furthermore, the bacteria in the oral cavity produce oxygen and nitrogen reactive species, as well as oncogenic metabolites (e.g., nitrosamines) to induce genetic damage to cells within the oral mucosa. Another mechanism by which neoplastic transformation is mediated by oral dysbiosis is via the alteration of epithelial barriers, which predispose the oral mucosa to the development of chronic pre-cancerous lesions. Oral dysbiosis is responsible for several epigenetic alterations, which promote the development of tumors (e.g., alteration of onco-miR or DNA methylation phenomena). Figure reprinted from “Association of oral dysbiosis with oral cancer development” by La Rosa et al licensed under CC BY 4.0; no changes were made to the figure. B - A recent report by Kamarajan et al documents an in vivo model in which periodontal pathogens, i.e. Treponema denticola (ATCC 35405), Porphyromonas gingivalis (ATCC 33277) and Fusobacterium nucleatum (ATCC 25586) and, their lipopolysaccharides activate TLR/MyD88-Integrin/FAK cross talk to promote cancer cell migration and invasion. Interestingly, nisin Z (Handary, Belgium), a bacteriocin produced by Lactococcus lactis inhibits the cancer formation. Image courtesy of Drs. Pachiyappan Kamarajan and Ryutaro Kuraji.

Fig. 5

Snapshots of biofilm composition at t = 60d receiving 6 glucose pulses per day, and a total daily amount of (a) 10 g/L/d and (b) 20 g/L/d. (a) Green spheres represent particles of a non-aciduric cell type (NA), and (b) red spheres represent those of an aciduric type (A). The computer simulations were initiated with 5% particles of type A and the remaining of type NA. Reproduced from Head et al. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 6

Networks of protein–protein interactions (PPIs) between Candida albicans (orange triangles), human oral proteins (blue diamonds), and proteins from other oral microorganisms (gray rectangles) are identified by gene name. Reprinted from Rosa et al. . (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)