Oral Metagenomic Biomarkers in Rheumatoid Arthritis

Overview

Rheumatoid Arthritis (RA) is a chronic and potentially severe autoimmune disease affecting 2 million in the United States. The role of environmental factors in modulating autoimmunity pathogenesis has been clearly described and yet the specific mechanisms of action remain poorly understood. A growing body of evidence implicates microbiota of mucosal surfaces in the development of autoimmune disorders. Various studies have clearly linked RA to periodontal disease. The latter is linked to the red-complex that includes the oral bacterium Porphyromonas gingivalis. And yet there has not been a systematic analysis of the oral microbiota in RA to determine whether there are specific markers for P. gingivalis (and other oral bacteria) that are linked to RA. In this study, the investigators will characterize oral microbial composition (microbiome) and gene content (metagenome) of DNA isolated from oral samples obtained from patients with (i) early stage RA prior to biologics treatments and (ii) subsets of RA patients who are responsive or unresponsive to anti-TNF-alpha therapy. The innovative aspect of this study is going beyond the identification of oral bacterial species, to the level of strains and genes that are associated with these groups. The overall hypothesis is that oral microbial variation exists between individuals that influences development of autoimmunity and autoimmune disease.

This is a multi-disciplinary research study with five investigators from different, yet complementary, disciplines to establish this new collaboration. There is a high translational potential for information gained from this project based on the collaboration of a rheumatologist, a dentist, oral biologists, and infectious disease experts with expertise in immunology, microbiology, and genomics. In brief, RA participants will be recruited by the rheumatologist. A total of 100 participants will be recruited for two groups to be studied; one group of subjects with RA and the other group will be healthy controls. These two groups will be divided into the following groups for participation in the study: Group 1: will consist of 25 RA adult subjects who have not been treated with biologics which will be compared to 25 healthy controls from age-matched members of the same household. Group 2 will consist of 25 RA adult subjects responsive to first line anti-TNF therapy which will be compared to 25 subjects of the same age and sex with RA who are resistant to two or more TNF antagonists. The participants will be scheduled for a research study visit at the University of Florida Dental Clinic Research Unit. During the exam the following will take place: the multidimensional health assessment questionnaire (MDHAQ), dental exam, saliva collection, and dental plaque will be removed from different tooth surfaces for supragingival. The supragingival will be subjected to deep sequencing in the genomics lab. To test two specific aims: 1) testing the hypothesis that oral microbiome profiles based on 16S RNA data are associated with the development of RA or with the response to a specific therapy, and 2) testing the hypothesis that the specific genes, variants, and functional capabilities (metagenome) are associated with RA or with therapeutic response. Upon completion of this pilot study, the investigators will have systematically identified bacterial biomarkers (e.g. species, subspecies, genes) that correlate with RA and may serve as potential targets for disease treatment. These markers may be developed into new drug targets for RA therapy in future studies.