Crohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) which represent a chronic, relapsing inflammation of the intestine. They are characterized by a defective mucosal barrier and increased intestinal permeability, the so-called “leaky gut”. Both environmental and genetic factors are associated with an increased risk to develop IBD.
Data from twin studies indicate that the genetic background may be responsible for 50% of the risk or “susceptibility” to develop CD. Genome wide association studies (GWAS) have identified more than 70 "risk" genes,, among them many genes involved in innate immune functions, such as the "pattern recognition receptor NLRP3"
However, obviously genetic susceptibility is not a sufficient condition as otherwise there would be 100% concordance of disease in monozygotic twin pairs. Environmental factors as well must play an important role. This is further supported by the fact that there is only low development in genetic risk factors over ten thousands of years. In contrast, the incidence of CD and UC has dramatically increased in Western countries in the last 100 years. This further supports the concept of “Western lifestyle factor(s)” that trigger chronic intestinal inflammation in a genetically susceptible host.
Microparticles are widely used as food additives or in pharmaceutical formulations and are consumed by millions of people. The most commonly used microparticles are sub-micron sized (0.1-1 μm diameter), inorganic compounds of titanium dioxide (TiO2, E171) aluminum silicate (AlSi, Kaolin, E559), silicon dioxide (SiO2, E551) and iron oxide (E172). The total daily intake of TiO2 in the Western world is estimated to be 76 mg. Indicators that TiO2 may have hazardous potential were found in animal and in vitro studies. In intestinal biopsies, aggregates of titanium were detected. These sites of titanium uptake correspond to regions where first signs of inflammation in Crohn’s disease (CD) manifest.
We have found that TiO2 particles are taken up by cells of the intestinal mucosa. The presence of TiO2 triggered inflammatory reaction in the mucosal cells.
Based on our recent findings we aim to further analyze
1) whether TiO2 is an environmental factor contributing to the pathogenesis of IBD
2) whether TiO2 may contribute to extraintestinal manifestations in IBD
3) whether there is evidence for other microparticles to activate inflammatory reactions
The long term goal will be a better understanding of mucosal tolerance and the development of new treatment options for chronic mucosal inflammatory diseases such as CD.