Oral polymicrobial communities: Assembly, function, and impact on diseases

Abstract

Oral microbial communities assemble into complex spatial structures. The sophisticated physical and chemical signaling systems underlying the community enable their collective functional regulation as well as the ability to adapt by integrating environmental information. The combined output of community action, as shaped by both intra-community interactions and host and environmental variables, dictates homeostatic balance or dysbiotic disease such as periodontitis and dental caries. Oral polymicrobial dysbiosis also exerts systemic effects that adversely affect comorbidities, in part due to ectopic colonization of oral pathobionts in extra-oral tissues. Here, we review new and emerging concepts that explain the collective functional properties of oral polymicrobial communities and how these impact health and disease both locally and systemically.

Keywords: caries; dysbiosis; inflammation; oral microbiome; periodontitis; spatial structure; systemic comorbidities.

Figure 1.. The spatial structure (biogeography) of oral polymicrobial communities.

The oral microbiota harbors a multitude of bacterial, fungal, viral, and even ultrasmall organisms distributed across different biotic and abiotic niches present in the mouth environment. These diverse communities can be found intermixed forming a variety of co-adhered or clustered populations as well as segregated spatial patterns which are modulated by cooperative or competitive interactions among community members. Pathogenic microbes, such as Streptococcus mutans, form highly organized polymicrobial communities, in which precise biogeography dictates positioning at the infection site (supragingival) and promotes a disease-causing state (dental caries). Complex physical and chemical interactions with different species promote a multilayered, corona-like spatial arrangement formed by an inner core composed of S. mutans clusters surrounded by EPS glucans and outer layers of other oral microbes. This spatial structure enhances bacterial fitness and protection and creates a highly acidic microenvironment, leading to localized onset of dental caries. Precise positioning and polymicrobial arrangement can coordinate the disease process in situ to create virulence hotspots that could serve as therapeutic targets.

Figure 2.. (A) Metabolic interactions among oral bacteria.

Green arrows represent a synergistic relationship whereby the metabolite increases the colonization, growth, or pathogenicity of a partner species. Red flat arrows represent a converse antagonistic relationship. The nature of the exchange may depend on a concentration gradient as depicted in the H₂O₂ interaction between Mitis Group Streptococci (MGS) and A. actinomycetemcomitans. MGS include the species S. gordonii, S. sanguinis, S. parasanguinis and S. mitis. (B) Outcomes of the interaction between MGS and A. actinomycetemcomitans or P. gingivalis.

Figure 3.. The interconnection of dysbiosis with inflammation as a disease driver.

Periodontitis results from reciprocally reinforced interactions between a dysbiotic microbiome and the host inflammatory response (Lamont et al., 2018). A dysbiotic microbiome can be stably transferred from diseased mice both vertically (to their offspring) and horizontally (to germ-free mice) and initiate periodontal disease (Payne et al., 2019). Inflammation exacerbates and sustains dysbiosis by creating a nutritionally favorable environment (e.g., tissue breakdown products such as degraded collagen and heme-containing compounds), thus supporting the chronification of the disease. Besides inflammation, other factors that contribute to the transformation of a eubiotic (in balance with the host) microbial community to a dysbiotic one, include host genetic factors, interspecies interactions that promote the colonization and metabolic support of keystone and pathobiont species, and keystone pathogen functions, such as subversion of host immunity (Hashim et al., 2021; Hoare et al., 2021; Maekawa et al., 2014).

Figure 4.. Gingival solitary chemosensory cells promote host-microbe homeostasis in the periodontium.

Gingival solitary chemosensory cells (gSCCs) express bitter taste receptors (Tas2r) and are present also in the sulcular and junctional epithelia, where they can detect quorum-sensing acyl-homoserine lactone (AHL) molecules released from periodontal bacteria. Activation of Tas2r in gSCCs leads to the induction of antimicrobial proteins (AMPs). This activity is required for host-microbe homeostasis, since genetic ablation of a Tas2r-associated signaling component (α-gustducin; Gnat3) causes dysbiotic alterations to the indigenous microbiota and naturally occurring periodontal bone loss (Zheng et al., 2019).

Figure 5.. Oral microbiome and extra-oral inflammatory conditions.

In periodontal disease, the ulceration of periodontal pockets facilitates the translocation of bacteria into the circulation, leading to bacteremia (and potentially bacterial dissemination to systemic tissues), systemic inflammation and metabolic alterations, which can affect comorbid conditions, such as, cardiovascular disease (CVD), non-alcoholic fatty liver disease (NAFLD) and Type 2 diabetes (T2D). Oral pathobionts swallowed via the oro-digestive route can translocate to the colon, where they can aggravate inflammatory bowel disease (IBD) in susceptible hosts, by activating local inflammatory responses, promoting dysbiosis and compromising barrier function (Kato et al., 2018; Kitamoto et al., 2020; Xing et al., 2022). This in turn may lead to endotoxemia, changes to the blood metabolome, and liver pathology (oral-gut-liver axis) (Imai et al., 2021; Xing et al., 2022; Yamazaki et al., 2021). Periodontitis-associated systemic comorbidities, in turn, increase the systemic inflammatory burden which can exacerbate microbial dysbiosis in the periodontium (Teles et al., 2021).