MedicalResearch.com Interview with:
Randy Longman, M.D. / Ph.D.
Assistant Professor of Medicine
Jill Roberts Center and Institute for Research in Inflammatory Bowel Disease
Weill Cornell Medicine
Division of Gastroenterology and Hepatology
Joan and Sanford I. Weill Department of Medicine
Department of Microbiology and Immunology
New York, NY 10021
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Inflammatory bowel disease is not limited to intestinal inflammation. Up to 1/3 of patients with active disease suffer from extra-intestinal manifestations.
The most common extra-intestinal manifestations in IBD is joint inflammation or spondyloarthritis. Peripheral joint spondyloarthritis carries a prevalence of 20% in Crohn’s Disease and 10% in Ulcerative Colitis, predominantly affecting joints of the lower limbs. It has long been suggested that gut bacteria can drive this systemic joint inflammation, but microbial targets have not been characterized.
MedicalResearch.com: What should readers take away from your report?
Response: Our work discovered that there are differences in the intestinal microbiome between patients with Crohn’s disease associated peripheral spondyloarthritis (SpA) and Crohn’s disease without SpA.
While several previous studies also identified signatures in the microbiome composition associated with inflammatory joint disease, we used a novel technique to sort and sequence IgA-coated microbiota to better understand which bacteria are immune-reactive. Using this technique, we found the enrichment of a pathotype of E. coli called adherent-invasive E. coli (AIEC) in the IgA-coated fraction of patients with CD-SpA. These patient derived AIEC trigger inflammatory Th17 cells in genetically susceptible mouse models of colitis and arthritis.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: There are few important clinical implications.
First, we show a correlation of a simple, patient reported disease activity index (called the Bath Ankylosing Spondylitis Disease Activity Index or BASDAI) with Enterobacteriaceae abundance in CD-SpA. This coupled with the increased abundance of IgA-coated adherent-invasive E. coli may allow us to develop diagnostic tools to stratify patients with symptoms as well as identify patients at risk. Importantly, our work highlights the activation of the IL-23 / Th17 pathway in patients with Crohn’s disease associated peripheral spondyloarthritis. With the recent approval of anti-IL-23 biologic therapy in Crohn’s disease, our findings may offer a guide for helping to select biologic therapy.
In addition, our study found the presence of a virulence gene called pduC in AIEC isolates from patients with CD-SpA. This gene allows these bacteria to forage for fucose metabolites abundant in the intestinal mucous layer and promote close association with the epithelial layer. When we genetically knockout this gene in one of our isolates, we prevent this bacteria from inducing Th17 cells. This exciting finding highlights a potential bacterial metabolic pathway that can be therapeutically targeted to alter Th17 induction.
MedicalResearch.com: Is there anything else you would like to add?
Response: While these data represent very exciting findings in a subset of patients with Crohn’s disease associated peripheral SpA, further work is needed to evaluate these findings in axial, HLA-B27+ associated disease as well as UC associated SpA. In addition, further studies are needed to evaluate the specificity of the immune cells within the inflamed joints.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Monica Viladomiu, Charles Kivolowitz, Ahmed Abdulhamid, Belgin Dogan, Daniel Victorio, Jim G. Castellanos, Viola Woo, Fei Teng, Nhan L. Tran, Andrew Sczesnak, Christina Chai, Myunghoo Kim, Gretchen E. Diehl, Nadim J. Ajami, Joseph F. Petrosino, Xi K. Zhou, Sergio Schwartzman, Lisa A. Mandl, Meira Abramowitz, Vinita Jacob, Brian Bosworth, Adam Steinlauf, Ellen J. Scherl, Hsin-Jung Joyce Wu, Kenneth W. Simpson, Randy S. Longman. IgA-coated E. coli enriched in Crohn’s disease spondyloarthritis promote T H 17-dependent inflammation. Science Translational Medicine, 2017; 9 (376): eaaf9655 DOI: 10.1126/scitranslmed.aaf9655
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