Role of Oral and Intestinal Microbiota in Rheumatoid Arthritis (RA)

Rheumatoid arthritis (RA) is an inflammatory form of arthritis that causes joint pain and damage. RA attacks the lining of the joints (synovium), causing swelling that can result in aching and throbbing, and eventually deformity. Even though there have been many advances in the treatment of RA, psoriatic arthritis (PsA), and other inflammatory arthritis, doctors still do not know what causes this inflammation in joints. It is likely that RA occurs as a result of a complex combination of factors, including a person's genes; lifestyle choices, such as smoking and diet; and things in a person's environment, including bacteria or viruses. This study investigates the hypothesis that bacteria living in a person's mouth and/or intestinal tract are responsible, at least in part, for the development of Rheumatoid Arthritis. The investigators believe that by killing those bacteria with antibiotics, they might be able to understand how the immune system works and, maybe, what causes RA.

If you would like to participate in this study, we will first ask you several questions regarding the status of your arthritis, the medications you use or have used in the recent past, your social and dietary habits, and your medical and surgical history. If your answers tell us that you are the right patient for our study, we will go over a consent form which describes in more detail how we will study your intestinal and mouth bacteria, the immune cells in your blood and other genes, enzymes and proteins that tell us about your disease status.

If you have Psoriatic Arthritis (PsA) or are healthy with no history of arthritis, and would like to participate in this study, your participation would involve only one or two visits, and no treatment.

If you have Rheumatoid Arthritis (RA), your participation would involve six visits, and you would be randomly assigned to receive treatment with the antibiotic doxycycline, or the antibiotic vancomycin, or no antibiotic treatment.

Eligibility Criteria:
Inclusion Criteria:

* Rheumatoid Arthritis (RA) patients must meet American College of Rheumatology (ACR) criteria for RA
* RA patients: duration of disease will be greater than 6 weeks and less than 2 years.
* RA patients should have a Disease Activity Score 28 (DAS28) greater than or equal to 5.
* PsA patients will be required to have disease duration and DAS28 similar to the RA patients, and to meet Moll and Wright criteria for PsA.
* Allowable medications for both groups at study entry will include: prednisone (or equivalent) 5 mg or less per day (stable dose for at least 2 months); methotrexate 15 mg or less per week (stable dose for at least 2 months); and nonsteroidal anti-inflammatory drugs (NSAIDs) at FDA-approved doses.
* Healthy controls will be age- and sex-matched individuals with no personal or family history of inflammatory arthritis.

Exclusion Criteria:

* Patients who are unable to provide informed consent.
* Pregnant or lactating women.
* Recent (\<3 months prior) use of any antibiotic therapy
* Current consumption of probiotics
* Current extreme diet (parenteral nutrition, macrobiotic diet, etc.)
* Prednisone \>5 mg/day or equivalent
* Use of other disease-modifying antirheumatic drugs (DMARDs) with known antibiotic properties (Gold salts, hydroxychloroquine, sulfasalazine or minocycline).
* Use of biologic DMARDs
* Known inflammatory bowel disease
* Known gastrointestinal (GI) tract neoplasm.
* Recent GI tract infection (gastroenteritis, colitis, diverticulitis, appendicitis)
* Chronic unexplained diarrhea.
* Any GI tract surgery leaving permanent residua (e.g., gastrectomy; bariatric surgery; colectomy)
* Significant liver, renal or peptic ulcer disease, defined as:

  * Liver: aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \> 2 x upper limit of normal (ULN)
  * Renal: Creatinine \>1.5 or endstage renal disease
  * Peptic ulcer disease: recent ulcer or GI bleed (within past 12 months)
* Inability or unwillingness to abstain from alcohol consumption.