The effect of iron chelation on the gut microbiome

Chelation Partners Inc. is developing a class of drugs that sequester iron, intended to enhance the activities ofantibiotics by preventing microbes from taking up iron. In early preclinical trials, Chelation Partners Inc.'s leaddrug proved to not adversely affect rat health when given orally. While this outcome is highly encouraging,whether the drug altered the animals' intestinal microbiome is unknown. Nor is it know whether the drugaffected the normal functions of the intestinal epithelium, though subclinically. It is possible that thecombination of changes in the microbiome with subclinical effects of iron chelation on epithelial cell biologyrenders the animal susceptible to a secondary challenge such as infection. The partners in this submission bringtogether the experience and capability to answer these questions. Dr. Stadnyk is an expert in intestinalepithelial pathophysiology, including extensive experience working with mouse models of induced intestinaldisease. In the first phase of the project Dr. Stadnyk will determine whether oral dosing mice with ChelationPartners Inc.'s lead drug changes the healthy animal's intestinal bacterial populations. This experiment will alsohelp establish a dosing of the drug to be used to determine whether chelating iron alters a mouse's susceptibilityto experimental chemical colitis. All the techniques and technologies to conduct the experiments are availableand active in Dr. Stadnyk's research network. Oral application of the drug is highly desirable but consideringthe growing awareness of the gut microbiome in human and animal health, it is critical to understand whetherthe drug alone (and therefore iron chelation as an adjuvant for antibiotics) has consequences on bacterialpopulations that possibly predispose the animals to illness.