Toxicological effects of metal oxide nanoparticles in combination with microbial components and inflammatory mediators on intestinal epithelial cells

Fredericks, Jorrell
Major Professor
Michael J. Wannemuehler
Anumantha Kanthasamy
Committee Member
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Veterinary Microbiology and Preventive Medicine

Inflammatory bowel disease (IBD) are inflammatory disorders with multi-factorial etiologies and many contributing factors (e.g., genetic disposition, luminal antigen, gut microbiota, and environment) that occur in about 1 in 300 persons in the United States and other western countries, but its etiology is still not well understood. Research has shown that maintenance of epithelial barrier plays an important role in mucosal homeostasis. Intestinal epithelial cells (IECs) play a critical role in formation and maintenance of the intestinal epithelial barrier which functions as a protective barrier from microbial components, environmental pollutants, food particles, and other luminal content and xenobiotics. As environmental factors can contribute to the onset or exacerbate the effects of IBD, there are not many studies investigating the impact of environmental factors, more specifically metal oxide nanoparticles found in the environment and food products, on the maintenance of the intestinal epithelial barrier. Furthermore, there are no studies investigating the impact of metal oxide nanoparticles in combination with microbial components or host inflammatory mediators on the health of intestinal epithelial cells.

Metal oxide nanoparticles, specifically manganese oxide nanoparticles (MnO NP) and titanium dioxide nanoparticles (TiO2 NP), are used in everyday life in a variety of applications, including welding, magnetic resonance imaging, drug delivery, and food products. Despite the gastrointestinal (GI) tract being the major route of excretion of metal oxide nanoparticles, studies that assess the toxicity of these nanoparticles on intestinal epithelial cells (IECs) and their interaction with components of the GI tract, such as the microbiota and host inflammatory mediators, are virtually nonexistent.

In this research, we examine the toxicity of MnO NP in conjunction with bacterial lysate on IECs and TiO2 NP in conjunction with host inflammatory mediators on IECs. In the studies in this dissertation, MODE-K cells, mouse intestinal epithelial cells, were exposed to nanoparticles (10 µg/ml MnO NP or 50 µg/ml TiO2 NP) alone or nanoparticles plus bacterial lysate or nanoparticle plus host inflammatory mediators for the duration of the experiment. Taken together, data suggests that toxicological effects of metal oxide nanoparticles (MnO NP and TiO2 NP) on intestinal epithelial cells were exacerbated in the presence of presence of microbial components and host inflammatory mediators.