Salivary Factors that Maintain the Normal Oral Commensal Microflora

Abstract

The oral microbiome is one of the most stable ecosystems in the body and yet the reasons for this are still unclear. As well as being stable, it is also highly diverse which can be ascribed to the variety of niches available in the mouth. Previous studies have focused on the microflora in disease-either caries or periodontitis-and only recently have they considered factors that maintain the normal microflora. This has led to the perception that the microflora proliferate in nutrient-rich periods during oral processing of foods and drinks and starves in between times. In this review, evidence is presented which shows that the normal flora are maintained on a diet of salivary factors including urea, lactate, and salivary protein degradation. These factors are actively secreted by salivary glands which suggests these factors are important in maintaining normal commensals in the mouth. In addition, the immobilization of SIgA in the mucosal pellicle indicates a mechanism to retain certain bacteria that does not rely on the bacterial-centric mechanisms such as adhesins. By examining the salivary metabolome, it is clear that protein degradation is a key nutrient and the availability of free amino acids increases resistance to environmental stresses.

Keywords: acetate; bacteria; metabolomics; mucosal pellicle; resilience; secretory IgA.

Figure 1.

The main bacterial substrates (blue box) and detected metabolites (indicated by boxes) in whole mouth saliva. The thickness of arrows and boxes indicates relative abundance, dotted lines indicate possible connections. Under resting conditions between meals, the products of the citric acid cycle (indicated by *) are largely undetectable. Most metabolites indicate the breakdown of salivary glycoproteins as the main nutrient source, the amino acids yielding acetate and propionate, the N- and O-linked glycans leading to pyruvate via the Embden Meyerhof Parnas (EMP) pathway.

Figure 2.

C¹³ labeled urea was added to whole mouth saliva and incubated for 1 h at 37°C. C¹³ nuclear magnetic resonance analysis revealed peaks assigned to ammonium carbamate and formate. In addition, propionate and acetate were detected of which only acetate was detected in the unlabeled control sample due to the natural abundance of C¹³ acetate isoform. The presence of ammonium carbamate and formate suggests urease is not active in reducing urea to ammonia. It is unclear how labeled propionate appeared or why formate is not further reduced to carbon dioxide by formate dehydrogenase (dotted box).

Figure 3.

Secretory IgA (SIgA) complexes with salivary mucins (Muc 5B and Muc 7) before binding to epithelial membrane–bound mucin Muc 1 to form the salivary mucosal pellicle. Secretory IgA can then mediate binding of bacteria (red rods and circles) helping them to adhere to epithelial cells. The mucin hydrogel–like properties of the mucosal pellicle allow concentration of bacterial products allowing quorum sensing and food networks that enhance their growth. As the epithelial surface is constantly sloughing, thick biofilms do not occur as they do in plaque around teeth. (Not drawn to scale).