The oral environment operates under a “different paradigm” from other parts of the GI tract, according to Richard Darveau. A key difference between the oral and intestinal environments, one with significant implications for differentiating health and disease, is that two-way communication between the inside and outside environments is a regular feature of even a healthy oral cavity. Unlike the intestinal epithelium, which is characterized by tight junctions, junctional epithelium in the oral cavity is very loosely organized. The looseness allows for constant neutrophil movement from the vasculature to the gingival crevice. Elsewhere in the GI tract, neutrophil movement is a sign of inflammation or disease. In the oral cavity, it is “normal.” Similarly, inflammatory cytokines are widely present in healthy mouths, where they play a key role in healthy tissue development and function. There are just “a lot more of them” in diseased mouths, Darveau explained. So the innate immune defense system is highly active even in healthy tissue. For example, Yoshioka and colleagues (2008) showed that plaque from both clinically healthy and diseased sites can stimulate both Toll-like receptor-2 (TLR-2)-mediated and TLR-4-mediated inflammatory responses. Darveau described disease as a “disruption in homeostasis,” that is, a disruption in the healthy relationship between oral microbes and the host tissue—one that causes increased inflammation and, eventually, bone and teeth loss (Darveau, 2010).
Constant movement across the junctional epithelium in the oral cavity, combined with the fact that the periodontium is a highly vascularized tissue, implicates periodontitis as a contributing factor to systemic disease. Darveau remarked that while the mechanisms are still unclear, researchers have reported clinical associations between dental and systemic diseases (Zelkha et al., 2010).
Another important difference between the oral and gut microbiomes is the ease of sampling the former. Scientists have conducted “thousands and thousands of analyses” of the oral microbiome, according to Darveau, providing the data to paint a good picture of healthy versus diseased oral bacterial consortia. A healthy oral bacterial consortium is characterized by mostly Gram-positive bacteria, whereas a periopathogenic bacterial consortium is characterized by mostly Gram-negative bacteria. Years ago, Darveau was involved in work that led to the identification of three of these Gram-negative bacteria collectively known as the “red complex bacteria”: Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola. The three species are associated both with each other and with periodontitis (Socransky et al., 1998). Much of Darveau’s research is on P. gingivalis, a
2 This section summarizes the presentation of Richard Darveau.