Defining the Harmful Effects of Microplastics on Gastrointestinal Health

Program Director/Principal Investigator: Castillo, Eliseo, F
PROJECT SUMMARY
Plastic pollution and the breakdown of plastic materials primarily into micron-sized microplastic particles (MP)
have contaminated our food and water sources, raising public health concerns. MP ingestion by humans is
now an inevitable consequence of global plastic pollution and there is a critical gap in knowledge as to how MP
impact human health (WHO). There is also an important gap in knowledge regarding how MP affect the major
direct organ of contact, the gastrointestinal (GI) tract. The studies proposed in this grant application seek to
bridge this gap in environmental health knowledge and provide insight into how MP pose a significant health
risk to the general population as well as susceptible (i.e. Inflammatory Bowel Disease; IBD) individuals. Our
preliminary data provides evidence chronic MP exposure affects the GI tract specifically causing gut dysbiosis,
low-level intestinal inflammation, and alterations in cellular metabolism. Based on our preliminary studies, we
advance a novel hypothesis that MP ingestion indeed pose a human health hazard by disrupting oxidative
metabolism in epithelial cells subsequently causing intestinal permeability, dysbiosis, and an immunometabolic
active state which could lead to intestinal inflammation. Additionally, we hypothesize MP ingestion pose a
significant health risk to individuals that have an underlying condition such as intestinal inflammation as seen in
IBD patients. The goals of this application are to investigate how MP induce cellular changes in intestinal
epithelial cells and to determine how these MP-induced changes in cellular pathways can lead to intestinal
permeability, dysbiosis and an inflammatory state. In aim 1, we will investigate the effects of varying doses and
types of MP on intestinal permeability in a zebrafish model. In Aim 2, we will determine the mechanism behind
MP induced dysbiosis and intestinal permeability. Aim 3 will delineate how an intact human intestinal tract
responds to microplastics through the use of human colonoids derived from health patients as well as IBD
patients. The information generated from this project would be a ground-breaking step with important long-term
implications in understanding how MP can affect intestinal homeostasis through modulation of epithelial barrier
function and overall human health.

Grant Number: 3R01ES032037-04S1
NIH Institute/Center: NIH
Principal Investigator: Eliseo Castillo