Clin Gastroenterol Hepatol. 2021 Mar 26;S1542-3565(21)00339-6.doi: 10.1016/j.cgh.2021.03.029. Online ahead of print.

Emily W Lopes ¹, Benjamin Lebwohl ², Kristin E Burke ¹, Kerry L Ivey ³, Ashwin N Ananthakrishnan ⁴, Paul Lochhead ¹, James M Richter ¹, Jonas F Ludvigsson ⁵, Walter C Willett ⁶, Andrew T Chan ⁷, Hamed Khalili ⁸

Author information

• ¹Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
• ²Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
• ³Department of Nutrition and Dietetics, College of Nursing and Health Sciences, Flinders University, Adelaide, Australia; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; South Australian Health and Medical Research Institute, Infection and Immunity Theme, School of Medicine, Flinders University, Adelaide, Australia.
• ⁴Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Clinical and Translation Epidemiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
• ⁵Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro University, Örebro, Sweden.
• ⁶Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
• ⁷Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Clinical and Translation Epidemiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
• ⁸Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Clinical and Translation Epidemiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts. Electronic address: hkhalili@mgh.harvard.edu.

Abstract

Background & aims: Diet is thought to play a role in the development of inflammatory bowel disease (IBD), although the relationship between gluten intake and risk of IBD has not been explored. The aim of this study was to determine the relationship between gluten intake and risk of incident Crohn's disease (CD) and ulcerative colitis (UC).

Methods: We performed a prospective cohort study of 208,280 US participants from the Nurses' Health Study (1986-2016), Nurses' Health Study II (1991-2017), and the Health Professionals Follow-up Study (1986-2016) who did not have IBD at baseline or celiac disease, and who completed semiquantitative food frequency questionnaires. We used Cox proportional hazards modeling to estimate the risk of IBD according to quintiles of cumulative average energy-adjusted dietary gluten intake over the follow-up period.

Results: We documented 337 CD cases and 447 UC cases over 5,115,265 person-years of follow-up evaluation. Dietary gluten intake was not associated with risk of IBD. Compared with participants in the lowest quintile of gluten intake, the adjusted hazard ratios and 95% CIs for participants in the highest quintile of gluten intake were 1.16 (95% CI, 0.82-1.64; P_trend = .41) for CD and 1.04 (95% CI, 0.75-1.44; P_trend = .64) for UC. Adjusting for primary sources of gluten intake did not materially change our estimates.

Conclusions: In 3 large adult US prospective cohorts, gluten intake was not associated with risk of CD or UC. Our findings are reassuring at a time when consumption of gluten has been increasingly perceived as a trigger for chronic gastrointestinal diseases.