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Therapeutic bubble tea: Preventing the formation of uremic toxins with hydrogel immobilized microbes

治疗性珍珠奶茶：利用水凝胶固定微生物预防尿毒症毒素的形成

基本信息

批准号：
10733487
负责人：
Mari-Karoliina Winkler
金额：
$ 1.03万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-01-01 至 2026-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10733487
关键词：
Aerobic Aftercare Alkanesulfonates American Amino Acids Bacteria Binding Binding Proteins Biological Biological Assay Biomedical Engineering Bioreactors Blood Blood Circulation Cardiovascular system Chemistry Chronic Kidney Failure Clinical Colon Communities Cresol Data Dialysis procedure Diffuse Diffusion Dose Drug Delivery Systems End stage renal failure Engineering Environment Environmental Engineering technology Excision Excretory function Fermentation Formulation Gastrointestinal tract structure Gel Goals Human Microbiome Hydrogels Immobilization Impaired cognition In Vitro Indican Indoles Ingestion Intestines Kidney Kidney Diseases Kidney Failure Kinetics Large Intestine Liver Mathematics Measures Membrane Metabolism Microbe Microbiology Morbidity - disease rate Needles Nutrient Oxygen Patient-Focused Outcomes Patients Performance Personal Satisfaction Plasma Plasma Albumin Polymer Chemistry Polymers Probiotics Research Residual state Running Science Side Site Small Intestines Source Stomach Sulfate Swelling Symptoms Tea Technology Testing Therapeutic Time Toxic effect Toxin Uremia Visualization absorption conventional therapy design experience experimental study gastrointestinal system gut microbiome high reward high risk improved improved outcome innovation mathematical model microbial microbiome microorganism microorganism culture mortality novel pH gradient particle preservation prevent protein degradation response scale up solute success symptomatology tool

项目摘要

Project summary Each year over 100,000 Americans begin dialysis when their kidneys lose the capacity to remove toxins from the blood and half of them die within five years. These high mortality rates are in part due to the ineffectiveness of dialysis at removing protein-bound uremic toxins (PBUTs) such as indoxyl sulfate and p-cresol sulfate, which would otherwise be removed by healthy kidneys. Herein, we propose a non-invasive ingestible bubble tea to reduce the blood concentration of PBUTs and improve the outcomes of patients with end stage kidney disease (ESKD). In contrast to conventional treatments, which attempt to remove toxins from the blood by dialysis, this research offers a radically different approach, which prevents the formation of toxins at their origin. PBUTs are byproducts of gut microbial metabolism; indole and p-cresol originate in the gut from fermentation of amino acids and both solutes are sulfonated in the liver to form the PBUTs indoxyl sulfate and p-cresol sulfate. We propose a novel microbe enriched bubble tea which will expand the capacity of the gut to degrade the uremic toxin (UT) precursors (indole and p-cresol) and thereby prevent their sulfonation to toxic forms in the liver. The bubble components will be engineered to remain tight in the stomach, hence protecting the hydrogel entrapped microbes from low pH, and then swell at neutral pH in the small intestine and colon, allowing UTs to diffuse into the hydrogel where the UT degrading microorganisms will deactivate them. Finally, the bubble tea will be excreted intact without altering the natural gut microbiome. This concept builds on the successful applications of microbe enriched hydrogels in bioengineering and environmental engineering for drug delivery and wastewater treatment. We will develop the bubble tea by first enriching novel indole and p-cresol degrading microbes from the environment, second engineering specialized hydrogel carriers for the microbes, and finally replicating their trip through the gut in well controlled bioreactor units. The substrate profiles, pH gradients, and removal rates will be experimentally measured and mathematically simulated to visualize spatial localization of bacteria and to determine UT degradation over time. Delivering these hydrogels in a formulated bubble tea drink could improve the lives of chronic kidney disease and ESKD patients by reducing the burden from uremic symptoms and complications.

项目总结