The culprit environmental substances include heavy and transition metals, air pollutants, pesticides, and industrial contaminants. The latter encompass synthetic chemicals such as perfluoroalkyls and polyfluoroalkyls (PFAs), which are present in many common household products.
In contrast, zinc exposure may have a protective, anti-inflammatory effect, according to a research group led by Maria Manuela Estevinho, MD, of the Department of Gastroenterology of the Unidade Local de Saúde Gaia e Espinho in Vila Nova de Gaia, Portugal.
Published in Gut , the review also found limited data suggesting adverse IBD outcomes such as hospitalizations are more prevalent with increased exposure to air contaminants in particular.
“These data carry relevance toward counseling patients and family members,” coauthor Manasi Agrawal, MD, assistant professor of medicine at the Icahn School of Medicine, Mount Sinai, and a gastroenterologist at Mount Sinai Hospital in New York City, said in an interview. “At the individual level, we can try to decrease our exposure to chemicals; for example, to minimize use of pesticides and products containing in our homes. However, at the broader community level, health policy changes are needed to help with mitigation strategies and curb production.”
Icahn School of Medicine at Mount Sinai
Dr. Manasi Agrawal
The physiological mechanisms by which pollutants raise IBD risk include an exaggerated immune response leading to systemic inflammation, loss of tight junction proteins leading to increased gut permeability, and dysbiosis of the intestinal microbiota.
The review found the following effects for various pollutants:
- Heavy and transition metals such as copper, lead, and cadmium were associated with gut dysbiosis, overgrowth of undesirable species of microorganisms, and loss of tight junction proteins leading to leaky gut. In all studies, individuals with IBD showed higher concentrations of such metals than healthy control individuals. While the specific profile of heavy metals varied across studies, lead, copper, and iron, were linked to IBD risk in more than one study.
- The particulate matter present in air pollution — including agricultural and wood dust as well as volcanic ash and hydrocarbon dioxin — was linked to dysbiosis and tight junction protein loss. Air pollution has also been linked to increased incidence of irritable bowel syndrome.
- Industrial and organic pollutants such as perfluoroalkyl and polyfluoroalkyl compounds, triclocarban, and polychlorinated biphenyls were also associated with gut permeability and/or reduced microbial diversity.
- Pesticides such as PFAs, organochloride and organophosphate compounds, and pyrethroids were associated with loss of tight junction proteins.
- Zinc was linked to an increase in tight junction proteins.
Commenting on the review but not involved in it, Ashwin N. Ananthakrishnan, MBBS, MD, MPH, AGAF, director of the Crohn’s and Colitis Center at Massachusetts General Hospital, and associate professor at Harvard Medical School in Boston, called it a very important study that expands our understanding of the role of environment in IBD.
Dr. Ashwin N. Ananthakrishnan
“While traditionally studies have focused on dietary and other exposures related to personal behavior and lifestyle such as smoking, this expands consideration to exposures at the environmental level, where an individual may have less control,” he said in an interview.
“This shift could be critically important from a policy standpoint as modifying these risk factors may require more societal than individual efforts,” he added. He did offer a caveat, however. “While the review highlights several plausible associations, all of which merit further study, importantly, one should also avoid overinterpreting the results as there are very few high-quality studies that provide robust evidence of an association. So more work is needed.”
Recent research has suggested that environmental exposures affect IBD risk more than genetic predisposition.
As background to this review, the growing industrialization and consumerism of the developing world has seen the global number of IBD cases rise from 3.3 million in 1990 to an estimated 4.9 million in 2019, a jump of 47.5%. In the United States, IBD accounts for more than $25 billion in direct healthcare costs.
In terms of the near future, Dr. Agrawal said, “Next steps would be to measure various chemicals in pre-disease biological samples for objective assessment of the impact of chemicals on IBD risk, and such studies are already underway.”
That would mean using exposure biomarkers with high temporal resolution in preclinical samples, as well as advanced measurement techniques and machine-based composite data analysis to explain the IBD-pollutant relationship. “This approach may also provide insight into the role of different environmental insults in different stages of life and clarify whether the timing of exposure may be more critical than the duration,” the authors wrote.
Dr. Agrawal was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the International Organization For the Study of Inflammatory Bowel Disease, and the Crohn’s and Colitis Foundation. She reported consulting for Douglas Pharmaceuticals. Other authors reported lecture/consulting fees from multiple pharmaceutical/biomedical companies. Dr. Ananthakrishnan had no relevant conflicts of interest.
A version of this article appeared on Medscape.com.