The Role of Short-Chain Fatty Acids Produced by Oral Bacteria in Modulating Oral Immunity

Dental plaque is a complex biofilm composed of various bacterial species. These bacteria metabolize nutrients, producing high concentrations of short-chain fatty acids (SCFAs) as metabolic by-products, including acetate, propionate, butyrate, isobutyrate, isovalerate, and others. SCFAs are also produced by colonic bacteria. Given that the concentration of SCFAs is significantly higher in the colon than in dental plaque, most of the existing literature focuses on the intestinal context. Following the discovery of SCFA receptors, transporters, and their histone deacetylase (HDAC) inhibitory activities, research on the effects of SCFAs on the immune system has gained increasing attention. Additionally, certain SCFAs induce cell death in periodontal tissues, leading to the release of intracellular molecules that act as damage-associated molecular patterns (DAMPs), thereby influencing the immune system. In this chapter, we first describe oral bacteria that produce SCFAs and compare the concentrations of these SCFAs in the oral cavity with those in the intestinal tract. Then, we provide an overview of the SCFA receptors, the transporters required for their transmembrane passage, and the histone deacetylase inhibitory effects of certain SCFAs. We then discuss how these mechanisms contribute to, or are hypothesized to influence, the effects of SCFAs on various immune cells. After reviewing various forms of cell death capable of triggering DAMP release, we will discuss the potential role of SCFA-induced gingival epithelial cell death in promoting the release of DAMPs and its contribution to gingival inflammation.