Commensal Gut-Derived Anaerobes as Novel Therapy for Inflammatory Autoimmune Diseases
Abstract
Predisposition to rheumatoid arthritis (RA) is associated with the presence of genetic factors, HLA class II molecules, DR4 and DQ8, being the strongest. Patients with RA show an imbalance of gut microbiota suggesting its role in regulation of disease. Recently, we isolated Prevotella histicola, anaerobic commensal bacteria of Human gut, from bowel of a patient and have shown that it possesses anti-inflammatory activity. We propose that gut microbiota can influence peripheral immune response and may modulate arthritis in a murine model. HLA transgenic mice expressing RA-susceptible genes DR4 and DQ8 develop collagen-induced arthritis (CIA) following immunization with type II collagen (CII). We have used HLA-DR4/ DQ8 mice to test our hypothesis that treatment with commensal bacteria like Prevotella histicola can modulate CIA. First using various doses of bacteria, we have identified the optimal dose for mice and then used that dose for treatment of arthritis. Treatment of mice with P. histicola as probiotics and therapy are ongoing. In vitro study showed that treatment of mice with P. histicola in CII-immunized mice led to suppression of antigen-specific immune response and reduction in production of inflammatory cytokines. Our data suggests that P histicola induced immune responses in the gut can induce tolerance in periphery leading to systemic immune suppression.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2011
- Accession Number
- ADA543751
Entities
People
- Venna Taneja
Organizations
- Mayo Clinic