Novel pH-Sensitive Particles for Noninvasive Upper GI Tract Microbiota Sampling

Applied Research Project 2 – Project Summary Research involving assessment of the upper gastrointestinal tract microbiota is restricted by the difficulty in being able to accurately sample this space noninvasively. Currently, animal experiments interested in probing this population requires sacrificing the animal, negating the possibility of longitudinal monitoring of the microbiome. This method is particularly problematic when exploring the impact of a medical intervention, pre/pro-biotic use, and/or dietary change where observation of alterations to the microbiota population over time are required. In this case, animal cohorts must be euthanized at each time point greatly increasing the number of animals used while not providing an actual internal standard for these longitudinal studies. There exists a considerable need for a technology that can facilitate the periodic and selective noninvasive sampling of the upper gastrointestinal tract. The long-term objective of our research is to leverage our expertise in materials engineering to create a novel microbiota capture system that selectively samples only the upper gastrointestinal tract before safely passing into the stool where it can be harvested and analyzed using a standard technique like 16S rRNA amplicon sequencing. Specific Aim 1 will build upon our previous efforts generating a pH-sensitive poly(amino acid)-grafted magnetic particle system to allow for the generation of different particle sizes with greater changes in pH-sensitive surface charge with the option to include antibody-mediated capture components to the particles. In Specific Aim 2, the in vitro, ex vivo, and in vivo performance of our first-generation upper gastrointestinal tract sampling technology, as well as follow-on generations of this technology, will be assessed. After selective capture has been achieved, longitudinal studies can be completed that will explore the impact antibiotic treatment alone or in combination with a fecal transplant have on the change of the upper gastrointestinal tract microbiota over time. The successful completion of these studies will not only yield a product that will have a tremendous impact on in the animal research community but could be readily translated for use in the clinic for companion animal, productional animal, and human applications in the relatively near future.