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

Award Number: R01DK130815
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $398,637 )
2024	2024	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	12/28/2023	NON-COMPETING CONTINUATION	$398,637
														Subtotal = $398,637

Issue Date FY: 2023 ( Subtotal = $471,311 )
2023	2023	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	1/13/2023	SUPPLEMENT FOR EXPANSION	$10,297
2023	2023	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	1/11/2023	NON-COMPETING CONTINUATION	$461,014
														Subtotal = $471,311

Issue Date FY: 2022 ( Subtotal = $483,157 )
2022	2022	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	12/24/2021	NEW	$475,802
2022	2022	UNIVERSITY OF WASHINGTON	4333 BROOKLYN AVE NE	SEATTLE	WA	98195	KING	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	9/1/2022	SUPPLEMENT FOR EXPANSION	$7,355
														Subtotal = $483,157

Grand Total All Awards = $1,353,105

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

Award Number: R01DK130815

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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