Microplastic biodistribution and impact on mental health during inflammatory bowel disease

About This Grant

PROPOSAL SUMMARY/ABSTRACT Global annual plastic production has grown significantly over the years, and plastic products are embedded in many facets of our daily lives. Microplastics (MPs) are small (< 500 mm) particles created during the breakdown of plastic materials. MPs are emerging as a significant environmental and public health risk due to their constant presence and consumption. Studies have shown that MPs consumed on a daily basis are known to distribute into multiple organ systems and illicit host-dependent responses, such as inflammation. MPs of various sizes are known to disrupt the intestinal barrier and promote tissue-dependent inflammation (e.g. neuroinflammation), leading to adverse events such as alterations in behavior linked by the gut-brain axis (GBA). In the current application, we propose conducting studies to determine how MP consumption impacts an animal model of inflammatory bowel disease (IBD). IBDs, such as ulcerative colitis (UC), refer to states of chronic inflammatory conditions in all or part of the gastrointestinal (GI) tract which results in increased intestinal permeability or “leaky gut”. IBDs such as UC are known to have extraintestinal manifestations (EIMs) such as alterations in mood or behavior, including development of depression. While growing research suggests that MP consumption can damage the GI barrier and distribute into various tissue/organ systems to promote inflammation, there are currently very few studies which focus on how MP consumption might impact an already weakened intestinal barrier due to colitis. The purpose of this application is to address this current unknown and generate preliminary data with the following specific aims: 1.) Assess depression-like behavior in a murine model of IBD after exposure to varied sizes of MPs; 2.) Develop a novel method for the quantification and visualization of MP localization in an IBD murine model. In order to complete these aims, this application proposes to test how consumption of MPs of varied sizes impact the dextran sodium sulfate (DSS) mouse model, a UC-like IBD animal model. In the first aim, we will test how MP consumption impacts colitis-associated depressive-like behavior and biomarkers of neuroinflammation. In the second aim, using the same model, we will next incorporate the use of tissue clearance and light sheet fluorescence microscopy (LSFM) to visualize and quantify biodistribution of MPs in various organs during an active colitis state. Results from these studies will help us better understand if MP consumption exacerbates colitis and colitis-related EIMs such as depression development and inflammation induced by deposition into other organs due to enhanced breakdown of the intestinal barrier.