Cariogenic Biofilm: Pathology-Related Phenotypes and Targeted Therapy

Abstract

The initiation and development of cariogenic (that is, caries-related) biofilms are the result of the disruption of homeostasis in the oral microenvironment. There is a daily accumulation of dental biofilm on the surface of teeth and its matrix of extracellular polymers supports the host in its defense against invading microbes, thus helping to achieve oral microbial homeostasis. However, the homeostasis can be broken down under certain circumstances such as during long-term exposure to a low pH environment which results in the dominance of acidogenic and acid-tolerating species in the dental biofilm and, thus, triggers the shift of harmless biofilm to an acidic one. This work aims to explore microbial diversity and the quorum sensing of dental biofilm and their important contributions to oral health and disease. The complex and multispecies ecosystems of the cariogenic biofilm pose significant challenges for the modulation of the oral microenvironment. Promising treatment strategies are those that target cariogenic niches with high specificity without disrupting the balance of the surrounding oral microbiota. Here, we summarized the recent advances in modulating cariogenic biofilm and/or controlling its pathogenic traits.

Strategies to Combat Caries by Maintaining the Integrity of Biofilm and Homeostasis during the Rapid Phase of Supragingival Plaque Formation

“…Normal supragingival biofilm development can, however, be affected by the various aforementioned factors, which the bacterial community will be unable to counteract by the homeostatic capacity, and, as a result of the ecological changes, the microbiota will be modified. An increase in carbohydrates in the environment to be metabolized by bacteria and the subsequent generation of a low environmental pH can change the composition and metabolic properties of the bacterial communities in dental plaque, leading to enrichment of acid producers (acidogenic) and acid-tolerant (aciduric) microorganisms [ 21 , 40 ]. The overgrowth of these bacteria and the excessive carbohydrate fermentation modify the oxygen gradient, creating a more anaerobic environment, thereby favoring rapid growth of pathogenic genera such as Porphyromonas , Tannerella , Treponema , Capnocytophaga and Aggregatibacter , which were present in very low latent numbers and were waiting for favorable conditions to grow in the biofilm [ 35 , 40 ].…”

“…An increase in carbohydrates in the environment to be metabolized by bacteria and the subsequent generation of a low environmental pH can change the composition and metabolic properties of the bacterial communities in dental plaque, leading to enrichment of acid producers (acidogenic) and acid-tolerant (aciduric) microorganisms [ 21 , 40 ]. The overgrowth of these bacteria and the excessive carbohydrate fermentation modify the oxygen gradient, creating a more anaerobic environment, thereby favoring rapid growth of pathogenic genera such as Porphyromonas , Tannerella , Treponema , Capnocytophaga and Aggregatibacter , which were present in very low latent numbers and were waiting for favorable conditions to grow in the biofilm [ 35 , 40 ]. In this dysbiotic condition, the supragingival biofilm could be the initial point for developing diseases other than caries, such as periodontal and peri-implant diseases [ 21 , 38 ].…”

“…In this scenario, the growth of certain species of P. gingivalis , Treponema denticola , Tannerella forsythia , and Aggregatibacter actinomycetemcomitans also produce other acids, such as lactic and formic acid [ 9 , 59 , 60 ], which complicate the situation. The accumulation of more diverse microbiota tolerant to an acidic environment on the supragingival surface of the tooth, along with elevated carbohydrate fermentation, disrupts the demineralization–remineralization balance of dental tissues, facilitating the onset of carious lesions [ 23 , 40 , 60 , 61 ].…”

“…The dysbiosis of supragingival biofilm also decreases the H 2 O 2 production of S. gordonii and reduces its competitiveness against Streptococcus mutans [ 37 , 45 ]. Likewise, the dysbiosis promotes the growth of cariogenic bacteria, such as S. mutans , Lactobacillus , Actinomyces , and Veillonella [ 21 , 39 , 40 ]. These bacteria produce lactic acid, which alters the exopolysaccharide matrix and modifies the chemical gradients that contribute to decreasing the pH of the medium.…”

“…This group of compounds includes sugar molecules that contain an amino group instead of a hydroxyl group in one of their radicals and those derivatives of amines that contain sugars, such as N-acetylglucosamine and sialic acid, which—although they formally do not contain primary amines—are also considered amino sugars [ 83 , 84 ]. It has been reported that amino sugars can enhance the beneficial properties of oral streptococci and can moderate the cariogenicity of oral biofilms without disturbing homeostatic balance [ 40 ]. Amino sugars such as glucosamine and N-acetylglucosamine can increase the competitiveness of S. gordonii against S. mutans , reducing the viability of S. mutans against other commensal species.…”