Oral microbiota dysbiosis accelerates the development and onset of mucositis and oral ulcers

Abstract

With the rapid development of metagenomic high-throughput sequencing technology, more and more oral mucosal diseases have been proven to be associated with oral microbiota shifts or dysbiosis. The commensal oral microbiota can greatly influence the colonization and resistance of pathogenic microorganisms and induce primary immunity. Once dysbiosis occurs, it can lead to damage to oral mucosal epithelial defense, thus accelerating the pathological process. As common oral mucosal diseases, oral mucositis and ulcers seriously affect patients' prognosis and quality of life. However, from the microbiota perspective, the etiologies, specific alterations of oral flora, pathogenic changes, and therapy for microbiota are still lacking in a comprehensive overview. This review makes a retrospective summary of the above problems, dialectically based on oral microecology, to provide a new perspective on oral mucosal lesions management and aims at improving patients' quality of life.

Keywords: dysbiosis; oral microbiota; oral mucositis; probiotics; recurrent aphthous stomatitis (RAS).

FIGURE 1

Differences between dysbiosis and homeostasis of mucosal microbiota: (A) the dysbiosis of microbiota could be symbolized by the impaired epithelium, thinner biofilm attached to the epithelium, and dominant microflora being pathogens. (B) Microbiota homeostasis could be characterized by intact epithelium, thicker biofilm, and commensal microflora instead. (This figure was partially cited from Lin et al. (2021) with modifications).

FIGURE 2

Factors leading to the microbiota shifts: (A) smoking exerts a significant influence on dysbiosis by microbiota carried by immune reaction inhibition and upregulation of IL-1/6 induced by receptor activator of nuclear factor- κβ Ligand (RANKL). (B) Radiotherapy could initiate oral mucositis induced by damage-associated molecular patterns (DAMPs) along with lipopolysaccharide (LPS). (C) Hematopoietic stem cell transplantation impacts the flora alterations in a way undiscovered.

FIGURE 3

Dysbiosis-induced immunoreaction: (a) innate immunity: lipopolysaccharide (LPS) and Peptidoglycan (PTG) contribute to the activation of immune and inflammatory responses in Th1/2. (b) Adaptive immunity: Porphyromonas gingivalis enhanced Th2 cytokine-mediated inflammatory immune response by prompting the secretion of IL-33 of epithelium, and antigen presentation by antigen–presenting cells (APCs) could activate Th1/2 by signal 1 and signal 2. (c) Candida albicans producing cytokines such as IL-1/IL-36 mediates the expression of IL-17 and the proliferation of Th17 cells, and short-chain fatty acids produced by microbiota facilitate the viability of Th17 with regulating the Tregs.

FIGURE 4

Microbiota in prevention and therapy of mucositis and ulcerations: (A) oral microbiota transplantation (OMT) was carried out in dogs and found that the relative abundance of Chlorobi g-1 sp., Neisseria sp., and Bergeyella sp. increased rather than α-diversity; while downregulating the Lactobacillaceae but increasing the α-diversity in mice. (B) Photobiomodulation therapy is demonstrated to inhibit the Haemophilus, Neisseria, and Prevotella, instead benefiting the commensal Streptococcus, meanwhile which is lethal to HSV-1, too. (C) Probiotics including Lactobacillus, Bifidobacterium, Escherichia coli, and Escherichia faecalis, could neutralize the lipopolysaccharide (LPS) of Porphyromonas gingivalis by secreting the reuterin and inhibiting Pasteurella and anaerobic bacteria by downregulating the expression of gene encoding nitrate reduction (napA).