Dataset Information

Oral Microbiome and Gingival Transcriptome Profiles of Ligature-Induced Periodontitis.

ABSTRACT: This investigation evaluated the relationship of the oral microbiome and gingival transcriptome in health and periodontitis in nonhuman primates (Macaca mulatta). Subgingival plaque samples and gingival biopsies were collected from healthy sites and at sites undergoing ligature-induced periodontitis. Microbial samples were analyzed with 16S amplicon sequencing to identify bacterial profiles in young (3 to 7 y) and adult (12 to 23 y) animals. The gingival transcriptome was determined with a microarray analysis and focused on the expression level of 452 genes that are associated with the development of inflammation and innate and adaptive immune responses. Of the 396 total operational taxonomic units (OTUs) identified across the samples, 81.8% were detected in the young group and 99.5% in the adult group. Nevertheless, 58 of the OTUs composed 88% of the signal in adults, and 49 OTUs covered 91% of the OTU readouts in the young group. Correlation analyses between the microbiome members and specific gingival genes showed a high number of significant bacteria-gene correlations in the young healthy tissues, which decreased by 75% in diseased tissues. In contrast, these correlations increased by 2.5-fold in diseased versus healthy tissues of adult animals. Complexes of bacteria were delineated that related to specific sets of immune genes, differing in health and disease and in the young versus adult animals. The correlated gene profiles demonstrated selected pathway overrepresentation related to particular bacterial complexes. These results provide novel insights into microbiome changes with disease and the relationship of these changes to specific gene profiles and likely biologic activities occurring in healthy and diseased gingival tissues in this human-like periodontitis model.

SUBMITTER: Ebersole J

PROVIDER: S-EPMC7243415 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:The epithelial barrier at mucosal sites comprises an important mechanical protective feature of innate immunity, and is intimately involved in communicating signals of infection/tissue damage to inflammatory and immune cells in these local environments. A wide array of antimicrobial factors (AMF) exist at mucosal sites and in secretions that contribute to this innate immunity. A non-human primate model of ligature-induced periodontitis was used to explore characteristics of the antimicrobial factor transcriptome (n = 114 genes) of gingival biopsies in health, initiation and progression of periodontal lesions, and in samples with clinical resolution. Age effects and relationship of AMF to the dominant members of the oral microbiome were also evaluated. AMF could be stratified into 4 groups with high (n = 22), intermediate (n = 29), low (n = 18) and very low (n = 45) expression in healthy adult tissues. A subset of AMF were altered in healthy young, adolescent and aged samples compared with adults (e.g., APP, CCL28, DEFB113, DEFB126, FLG2, PRH1) and were affected across multiple age groups. With disease, a greater number of the AMF genes were affected in the adult and aged samples with skewing toward decreased expression, for example WDC12, PGLYRP3, FLG2, DEFB128, and DEF4A/B, with multiple age groups. Few of the AMF genes showed a >2-fold increase with disease in any age group. Selected AMF exhibited significant positive correlations across the array of AMF that varied in health and disease. In contrast, a rather limited number of the AMF significantly correlated with members of the microbiome; most prominent in healthy samples. These correlated microbes were different in younger and older samples and differed in health, disease and resolution samples. The findings supported effects of age on the expression of AMF genes in healthy gingival tissues showing a relationship to members of the oral microbiome. Furthermore, a dynamic expression of AMF genes was related to the disease process and showed similarities across the age groups, except for low/very low expressed genes that were unaffected in young samples. Targeted assessment of AMF members from this large array may provide insight into differences in disease risk and biomolecules that provide some discernment of early transition to disease.

Project description:Although data describe the presence and increase of inflammatory mediators in the local environment in periodontitis vs. health in humans, details regarding how these responses evolve in the transition from health to disease, changes during disease progression, and features of a resolved lesion remain unknown. This study used a nonhuman primate model of ligature-induced periodontitis in young, adolescent, adult, and aged animals to document features of inflammatory response affected by age. Rhesus monkeys had ligatures tied and provided gingival tissue biopsy specimens at baseline, 0.5, 1, and 3 months of disease and at 5 months of the study, which was 2 months post-ligature removal for clinically resolved tissues. The transcriptome was assessed using microarrays for chemokine (n = 41), cytokine (n = 45), chemokine receptor (n = 21), cytokine receptor (n = 37), and lipid mediator (n = 31) genes. Limited differences were noted in healthy tissues for chemokine expression with age; however, chemokine receptor genes were decreased in young but elevated in aged samples. IL1A, IL36A, and IL36G cytokines were decreased in the younger groups, with IL36A elevated in aged animals. IL10RA/IL10RB cytokine receptors were altered with age. Striking variation in the lipid mediator genes in health was observed with nearly 60% of these genes altered with age. A specific repertoire of chemokine and chemokine receptor genes was affected by the disease process, predominated by changes during disease initiation. Cytokine/cytokine receptor genes were also elevated with disease initiation, albeit IL36B, IL36G, and IL36RN were all significantly decreased throughout disease and resolution. Significant changes were observed in similar lipid mediator genes with disease and resolution across the age groups. Examination of the microbiome links to the inflammatory genes demonstrated that specific microbes, including Fusobacterium, P. gingivalis, F. alocis, Pasteurellaceae, and Prevotella are most frequently significantly correlated. These correlations were generally positive in older animals and negative in younger specimens. Gene expression and microbiome patterns from baseline were distinctly different from disease and resolution. These results demonstrate patterns of inflammatory gene expression throughout the phases of the induction of a periodontal disease lesion. The patterns show a very different relationship to specific members of the oral microbiome in younger compared with older animals.

Dataset Information

Oral Microbiome and Gingival Transcriptome Profiles of Ligature-Induced Periodontitis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets