Elevated risk of adverse effects from foodborne contaminants and drugs in inflammatory bowel disease: a review

Abstract

The global burden of Inflammatory bowel disease (IBD) has been rising over the last decades. IBD is an intestinal disorder with a complex and largely unknown etiology. The disease is characterized by a chronically inflamed gastrointestinal tract, with intermittent phases of exacerbation and remission. This compromised intestinal barrier can contribute to, enhance, or even enable the toxicity of drugs, food-borne chemicals and particulate matter. This review discusses whether the rising prevalence of IBD in our society warrants the consideration of IBD patients as a specific population group in toxicological safety assessment. Various in vivo, ex vivo and in vitro models are discussed that can simulate hallmarks of IBD and may be used to study the effects of prevalent intestinal inflammation on the hazards of these various toxicants. In conclusion, risk assessments based on healthy individuals may not sufficiently cover IBD patient safety and it is suggested to consider this susceptible subgroup of the population in future toxicological assessments.

Keywords: Chemically-induced disorders; Crohn’s disease; Drug-related side effects and adverse reactions; Foodborne illnesses; Inflammatory bowel disease; Ulcerative colitis.

Fig. 1

Dietary toxicity in IBD patients. Detrimental dietary additives, such as artificial sweeteners, emulsifiers and engineered nanomaterials (ENM) are able to enter the intestinal lamina propria as the epithelial barrier function is compromised, which can lead to activation of the immune system. Furthermore, these dietary compounds can disturb the microbiome, leading to further exacerbation of IBD. Biotoxins derived from pathogenic microbes such as C. difficile enter the lamina propria where they can further damage the intestine, as well as enter the systemic circulation. Created with BioRender.com

Fig. 2

Chemical toxicity in IBD patients. Various chemicals have proven to have a deleterious effect on gut health of individuals with IBD. For example, Propyzamide inhibits AhR signaling leading to tight junction (TJ) disruption. The pesticide chlorpyrifos has been found to alter gut microbiome composition and to disturb T_reg17/T_h17 balance, resulting in increased inflammation. Endocrine-disrupting chemicals such as bisphenol A have been found to aggravate IBD. Aluminium has shown to worsen colitis, and decrease epithelial regeneration in mice. Created with BioRender.com

Fig. 3

Altered transporter expression levels in IBD patients, divided into apical and basolateral transport. Upregulated transporters are shown in yellow, while downregulated transporters are shown in purple. Created with BioRender.com

Fig. 4

Toxicity induced by pharmaceuticals in IBD patients. The compromised epithelial barrier in IBD patients results in increased uptake of compounds. Chemotherapeutics are cytotoxic to the intestinal epithelium, releasing damage associated proteins leading to increased inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) damage the intestinal epithelium by disrupting oxidative phosphorylation, and prevent tissue repair via COX inhibition. Proton pump inhibitors increase the luminal pH, leading to gut microbial dysbiosis. Antibiotics cause dysregulation of both the immune response and the gut microbiome. Selective serotonin reuptake inhibitors (SSRIs), inhibit serotonin (5-HT) reuptake by enterocytes by blocking selective serotonin reuptake inhibitors. The increased 5-HT concentration in the lamina propria results in immune cell activation, which leads to increased intestinal inflammation. Created with BioRender.com