Titanium dioxide particles from the diet: involvement in the genesis of inflammatory bowel diseases and colorectal cancer

Abstract

The gastrointestinal tract is a complex interface between the external environment and the immune system. Its ability to control uptake across the mucosa and to protect the body from damage of harmful substances from the lumen is defined as the intestinal barrier function (IBF). The IBF involves four elements: the intestinal microbiota, the mucus layer, the epithelium and the immune system. Its dysfunction is linked with human diseases including inflammatory, metabolic, infectious, autoimmune and neurologic disorders. Most of these diseases are complex and involve genetic, psychological and environmental factors. Over the past 10 years, many genetic polymorphisms predisposing to inflammatory bowel disease (IBD) have been identified. Yet, it is now clear that they are insufficient to explain the onset of these chronic diseases. Although it has been evidenced that some environmental factors such as cigarette smoking or carbohydrate intake are associated with IBD, other environmental factors also present potential health risks such as ingestion of food additives introduced in the human diet, including those composed of mineral particles, by altering the four elements of the intestinal barrier function. The aim of this review is to provide a critical opinion on the potential of TiO2 particles, especially when used as a food additive, to alter the four elements of the intestinal barrier function, and consequently to evaluate if this additive would likely play a role in the development and/or exacerbation of IBD.

Intestinal Microecology of Mice Exposed to TiO2 Nanoparticles and Bisphenol A

“…Our data indicate that the combination of TiO 2 NPs and BPA causes intestinal microbial dysregulation in mice, in which TiO 2 NPs play a critical role in microbial dysbiosis. Previously, TiO 2 NP-induced alterations in the gut microbiota have been reported to be associated with IBD [ 7 ]. Therefore, we hypothesised that the gut microbial dysbiosis caused by TiO 2 NPs and BPA might be related to IBD.…”

“…Microbial dysbiosis can aggravate various diseases, including diabetes, obesity, Crohn’s disease, and inflammatory bowel disease [ 1 , 4 , 5 , 6 ]. In addition, the gut microbiota is highly sensitive to exogenous stressors, including nanoparticles (NPs) and persistent organic pollutants (POPs) [ 7 , 8 , 9 , 10 ].…”

“…The intestine, the longest residence organ for TiO 2 NPs following their ingestion, is the most sensitive. Some studies have demonstrated that the long-term oral use of foods containing TiO 2 NPs may increase the risk of colorectal cancer [ 7 ]. In vitro studies have shown that TiO 2 NPs have antimicrobial activity and can promote the production of reactive oxygen species [ 22 , 23 ].…”

Food-Grade Titanium Dioxide Induces Toxicity in the Nematode Caenorhabditis elegans and Acute Hepatic and Pulmonary Responses in Mice

“…Once ingested, TiO 2 NPs can cross biological membranes, enter cells, and accumulate in tissues and organs, where they exert toxicity and can trigger both local and systemic responses [ 24 ]. In addition, once it enters the circulation, E171 perfuses all peripheral organs (including the lungs and liver), accumulating in the digestive organs and impairing gastrointestinal functions [ 25 ]. It can also accumulate in the reproductive system, pass through the placenta, and be transferred from maternal to fetal circulation [ 24 , 25 , 26 , 27 , 28 ].…”

“…In addition, once it enters the circulation, E171 perfuses all peripheral organs (including the lungs and liver), accumulating in the digestive organs and impairing gastrointestinal functions [ 25 ]. It can also accumulate in the reproductive system, pass through the placenta, and be transferred from maternal to fetal circulation [ 24 , 25 , 26 , 27 , 28 ].…”