Role of sulfide in oral microbiota-host interactions that promote periodontitis

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PROJECT SUMMARY/ABSTRACT (for administrative supplement to parent R00 award from NIDCR) Periodontal (gum) disease is one of the most prevalent inflammatory diseases worldwide, affecting nearly 50% of adults in the US alone. Untreated, periodontitis can erode the tissues that support the teeth, ultimately resulting in tooth loss, as well as increased risk for several co-morbidities (e.g., diabetes, heart disease, and cancer). In contrast to classic infectious diseases, periodontitis is triggered by the outgrowth of multiple (rather than individual) “pathogens” - pro-inflammatory, normally low-level constituents of the oral-cavity microbiota. These pathogens expand by metabolically exploiting local tissue damage, while also excreting metabolites that sustain further inflammation. A key example is hydrogen sulfide. This pro-inflammatory metabolite is produced in prolific amounts by periodontal pathogens, due to their increased access to tissue damage-derived, sulfur-containing amino acids - cysteine, methionine, and taurine. In our funded parent award (R00 through NIDCR), we focus on cysteine/methionine and a particular mechanism by which their degradation to sulfide, specifically by the pathogen Fusobacterium nucleatum, can potentially exacerbate periodontitis: inflammation triggered by F. nucleatum-derived sulfide constructs a metabolic niche that enables expansion of a prominent co-pathogen (Aggregatibacter actinomycetemcomitans). Unlike F. nucleatum, other pathogens within the oral microbiota can degrade taurine. Yet, whether sulfide from taurine-degrading pathogens can also contribute to periodontitis has not been explored. This is particularly concerning since taurine is widely consumed as a dietary supplement due to its many purported health benefits. Indeed, in a project supported by the Office of Dietary Supplements (ODS) Research Scholars Program, we recently reported that when provided prophylactically, dietary taurine-derived sulfide can enhance the microbiota’s resistance to invading pathogens. However, in the context of pre-existing inflammation, such as periodontitis, taurine-derived sulfide may instead exacerbate disease. In this ODS administrative supplement, we propose testing this exact possibility. Falling within the scope of our original award, we propose testing whether by a similar mechanism as the cysteine/methionine-degrading pathogen F. nucleatum, the taurine-degrading pathogen Bilophila wadsworthia can enhance periodontal disease. This new information will enhance our original award because it will demonstrate that sulfide’s negative impact on oral health is not restricted to a specific periodontal pathogen (not only F. nucleatum but also B. wadsworthia) nor a specific sulfide precursor (not only cysteine/methionine but also taurine). Most importantly, the new information that will be generated by this administrative supplement will shed light on the potential health risks of a widely consumed dietary supplement (the amino acid taurine) and a context (the prevalent disease periodontitis) in which consumption of this supplement should be avoided.