Abstract
Significance
Experimental gingivitis studies where dental hygiene is withheld from select teeth, allowing natural bacterial accumulation, provide a unique opportunity to study the reversible transition from health to inflammatory disease in humans. Longitudinal analysis of both the microbial and host changes during human experimental gingivitis revealed a previously unknown variation in the human host response and microbial succession sequence during inflammation. The significance of our findings can be summarized in two major points. First, the study comprehensively characterizes three different clinical responses—designated high, low, and slow—discerning unique host and microbial features that define each group. Second, we have unveiled previously unrecognized host protective mechanisms to prevent inflammatory bone resorption during reversible gingival inflammation.
Oral commensal bacteria actively participate with gingival tissue to maintain healthy neutrophil surveillance and normal tissue and bone turnover processes. Disruption of this homeostatic host–bacteria relationship occurs during experimental gingivitis studies where it has been clearly established that increases in the bacterial burden increase gingival inflammation. Here, we show that experimental gingivitis resulted in three unique clinical inflammatory phenotypes (high, low, and slow) and reveal that interleukin-1β, a reported major gingivitis-associated inflammatory mediator, was not associated with clinical gingival inflammation in the slow response group. In addition, significantly higher levels of
Streptococcus
spp. were also unique to this group. The low clinical response group was characterized by low concentrations of host mediators, despite similar bacterial accumulation and compositional characteristics as the high clinical response group. Neutrophil and bone activation modulators were down-regulated in all response groups, revealing novel tissue and bone protective responses during gingival inflammation. These alterations in chemokine and microbial composition responses during experimental gingivitis reveal a previously uncharacterized variation in the human host response to a disruption in gingival homeostasis. Understanding this human variation in gingival inflammation may facilitate the identification of periodontitis-susceptible individuals. Overall, this study underscores the variability in host responses in the human population arising from variations in host immune profiles (low responders) and microbial community maturation (slow responders) that may impact clinical outcomes in terms of destructive inflammation.