Challenges in IBD Research: Environmental Triggers

Author:

Ho Shuk-Mei1,Lewis James D2,Mayer Emeran A3,Bernstein Charles N4,Plevy Scott E5,Chuang Emil6,Rappaport Stephen M7,Croitoru Kenneth8,Korzenik Joshua R9,Krischer Jeffrey10,Hyams Jeffrey S11,Judson Richard12,Kellis Manolis13,Jerrett Michael2,Miller Gary W14,Grant Melanie L15,Shtraizent Nataly16,Honig Gerard16,Hurtado-Lorenzo Andrés16,Wu Gary D2

Affiliation:

1. University of Cincinnati, Cincinnati, Ohio

2. Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

3. University of California Los Angeles, Los Angeles, California

4. Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada

5. Synlogic, Cambridge Massachusetts, Massachusetts

6. Progenity, San Diego, California

7. University of California Berkeley, Berkeley, California

8. Mount Sinai Hospital, University of Toronto, Toronto, Canada

9. Brigham and Women’s Hospital, Boston, Massachusetts

10. University of South Florida, Tampa, Florida

11. Connecticut Children’s Medical Center, Hartford, Connecticut

12. United States Environmental Protection Agency, Washington, District of Columbia

13. Massachusetts Institute of Technology, Cambridge, Massachusetts

14. Columbia University, New York, New York

15. Children’s National Health System, Washington, District of Columbia

16. Crohn’s & Colitis Foundation, New York, New York

Abstract

Abstract Environmental triggers is part of five focus areas of the Challenges in IBD research document, which also includes preclinical human IBD mechanisms, novel technologies, precision medicine and pragmatic clinical research. The Challenges in IBD research document provides a comprehensive overview of current gaps in inflammatory bowel diseases (IBD) research and delivers actionable approaches to address them. It is the result of a multidisciplinary input from scientists, clinicians, patients, and funders, and represents a valuable resource for patient centric research prioritization. In particular, the environmental triggers section is focused on the main research gaps in elucidating causality of environmental factors in IBD. Research gaps were identified in: 1) epidemiology of exposures; 2) identification of signatures of biological response to exposures; and 3) mechanisms of how environmental exposures drive IBD. To address these gaps, the implementation of longitudinal prospective studies to determine disease evolution and identify sub-clinical changes in response to exposures is proposed. This can help define critical windows of vulnerability and risk prediction. In addition, systems biology analysis and in silico modeling were proposed as approaches to integrate the IBD exposome for the identification of biological signatures of response to exposures, and to develop prediction models of the effects of environmental factors in driving disease activity and response to therapy. This research could lead to identification of biomarkers of exposures and new modalities for therapeutic intervention. Finally, hypothesis-driven mechanistic studies to understand gene-environment interactions and to validate causality of priority factors should be performed to determine how environment influences clinical outcomes.

Funder

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Gastroenterology,Immunology and Allergy

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