Gut. 2025 Feb 6;74(3):477-486. doi: 10.1136/gutjnl-2024-332523.

Maria Manuela Estevinho ^1 2, Vishal Midya ³, Shirley Cohen-Mekelburg ^4 5, Kristine Højgaard Allin ^6 7, Mathurin Fumery ⁸, Salome S Pinho ^9 10 11, Jean-Frederic Colombel ¹², Manasi Agrawal ^13 12

Author information

¹Department of Gastroenterology, Unidade Local de Saúde Gaia Espinho, Vila Nova de Gaia, Portugal.

²Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal.

³Department of Environmental Medicine and Climate Science, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

⁴Division of Gastroenterology and Hepatology, University of Michigan Medicine, Ann Arbor, Michigan, USA.

⁵VA Center for Clinical Management Research, VA Ann Arbor Health Care System, Ann Arbor, Michigan, USA.

⁶Center for Molecular Prediction of Inflammatory Bowel Disease (PREDICT), Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark.

⁷Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.

⁸Department of Gastroenterology, CHU Amiens and PériTox, UMR-I 01 INERIS, Picardie Jules Verne University, Amiens, France.

⁹i3S, Institute for Research and Innovation in Health, Porto, Portugal.

¹⁰ICBAS-School of Medicine and Biomedical Sciences, Porto, Portugal.

¹¹Faculty of Medicine, University of Porto, Porto, Portugal.

¹²The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

¹³Center for Molecular Prediction of Inflammatory Bowel Disease (PREDICT), Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark manasi.agrawal@mountsinai.org.

Abstract

Epidemiological and translational data increasingly implicate environmental pollutants in inflammatory bowel disease (IBD). Indeed, the global incidence of IBD has been rising, particularly in developing countries, in parallel with the increased use of chemicals and synthetic materials in daily life and escalating pollution levels. Recent nationwide and ecological studies have reported associations between agricultural pesticides and IBD, particularly Crohn's disease. Exposure to other chemical categories has also been linked with an increased risk of IBD. To synthesise available data and identify knowledge gaps, we conducted a systematic review of human studies that reported on the impact of environmental pollutants on IBD risk and outcomes. Furthermore, we summarised in vitro data and animal studies investigating mechanisms underlying these associations. The 32 included human studies corroborate that heavy and transition metals, except zinc, air pollutants, per- and polyfluorinated substances, and pesticides are associated with an increased risk of IBD, with exposure to air pollutants being associated with disease-related adverse outcomes as well. The narrative review of preclinical studies suggests several overlapping mechanisms underlying these associations, including increased intestinal permeability, systemic inflammation and dysbiosis. A consolidated understanding of the impact of environmental exposures on IBD risk and outcomes is key to the identification of potentially modifiable risk factors and to inform strategies towards prediction, prevention and mitigation of IBD.