Immunoglobulin gene expression profiles and microbiome characteristics in periodontitis in nonhuman primates.

Colonization of mucosal tissues throughout the body occurs by a wide array of bacteria in the microbiome that stimulate the cells and tissues, as well as respond to changes in the local milieu. A feature of periodontitis is the detection of adaptive immune responses to members of the oral microbiome that show specificity and changes with disease and treatment. Thus, variations in antibody responses are noted across the population and affected by aging, albeit, data are still unclear as to how these differences relate to disease risk and expression. This study used a nonhuman primate model of experimental periodontitis to track local microbiome changes as they related to the use and expression of a repertoire of immunoglobulin genes in gingival tissues. Gingival tissue biopsies from healthy tissues and following ligature-placement for disease initiation and progression provided gene expression analysis. Additionally, following removal of the ligatures, clinical healing occurs with gene expression in disease resolved tissues. Groups of 9 animals (young: <3 yrs., adolescent: 3-7 yrs., adult -12 to 15 yrs.; aged: 17-22 yrs) were used in the investigation. In healthy tissues, young and adolescent animals showed levels of expression of 78 Ig genes that were uniformly less than adults. In contrast, ⅔ of the Ig genes were elevated by > 2-fold in the aged samples. Specific increases in an array of the Ig gene transcripts were detected in adults at disease initiation and throughout progression, while increases in young and adolescent animals were observed only with disease progression, and in aged samples primarily late in disease progression. Resolved lesions continued to demonstrate elevated levels of Ig gene expression in only young, adolescent and adult animals. The array of Ig genes significantly correlated with inflammatory, tissue biology and hypoxia genes in the gingival tissues, with variations associated with age. In the young group of animals, specific members of the oral microbiome positively correlated with Ig gene expression, while in the older animals, many of these correlations were negative. Significant correlations were observed with a select assortment of bacterial OTUs and multiple Ig genes in both younger and older animal samples, albeit the genera/species showed little overlap. Incorporating this array of microbes and host responses clearly discriminated the various time points in transition from health to disease and resolution in both the young and adult animals. The results support a major importance of adaptive immune responses in the kinetics of periodontal lesion formation, and support aging effects on the repertoire of Ig genes that may relate to the increased prevalence and severity of periodontitis with age.