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Microbiota-based probiotics to treat inborn errors in metabolism

Award Number: R01AT011396
ORGANIZATION: CENTER FOR DRUG EVALUATION AND RESEARCH, NIH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/16/2022
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Microbiota-based probiotics to treat inborn errors in metabolism - Project Summary/Abstract The human gut is a metabolic organ where anaerobic microbial pathways run at high capacity, expanding the biochemical landscape of the human body. Exploiting members of the gut microbiota and the metabolic pathways they encode represents an exciting new strategy to treat genetically encoded biochemical defects in humans such as Phenylketonuria. There are three reasons why identifying new microbiota probiotics should be a priority: 1) Gut microbes represent an important yet untapped resource for new metabolic pathways that influence human biochemistry. 2) Microbiota pathways are present in healthy individuals, and their metabolic end products are unlikely to be toxic to humans. 3) Native, non-genetically modified strains are likely to have a straightforward regulatory pathway for use in humans. While this proposal is focused on identifying microbes and pathways to reduce blood phenylalanine levels to treat phenylketonuria, our long-term goal is to lay the foundation for an entirely new approach to treat inborn errors in metabolism: controlling metabolic circuits via the gut microbiota. Our proposal is organized into the following two aims: In Aim 1, we will use gene cluster searches, transcriptomics, genetics, and metabolomics to identify and characterize anaerobic pathways for phenylalanine metabolism by gut bacteria. In Aim 2, we will assess the ability of microbial pathways to reduce plasma Phe levels in a gnotobiotic mouse model of phenylketonuria (PKU). Our results will not only provide new insights into how the microbiome expands the biochemical landscape of the host but will also lay the groundwork for a new approach to treating inborn errors in metabolism.


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: 2026 ( Subtotal = $587,879 )
2026	2026	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Research and Training in Complementary and Integrative Health	000	5	3/23/2026	NON-COMPETING CONTINUATION	$587,879
														Subtotal = $587,879

Issue Date FY: 2025 ( Subtotal = $529,091 )
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Research and Training in Complementary and Integrative Health	000	4	1/17/2025	NON-COMPETING CONTINUATION	$529,091
														Subtotal = $529,091

Issue Date FY: 2024 ( Subtotal = $576,120 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Research and Training in Complementary and Integrative Health	002	3	5/21/2024	NON-COMPETING CONTINUATION	$0
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Research and Training in Complementary and Integrative Health	001	3	5/13/2024	NON-COMPETING CONTINUATION	$47,029
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Research and Training in Complementary and Integrative Health	000	3	1/11/2024	NON-COMPETING CONTINUATION	$529,091
														Subtotal = $576,120

Issue Date FY: 2023 ( Subtotal = $587,879 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Research and Training in Complementary and Integrative Health	000	2	1/24/2023	NON-COMPETING CONTINUATION	$558,486
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Research and Training in Complementary and Integrative Health	001	2	3/24/2023	NON-COMPETING CONTINUATION	$29,393
														Subtotal = $587,879

Issue Date FY: 2022 ( Subtotal = $587,879 )
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Research and Training in Complementary and Integrative Health	000	1	2/16/2022	NEW	$587,879
														Subtotal = $587,879

Grand Total All Awards = $2,868,848

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Microbiota-based probiotics to treat inborn errors in metabolism

Award Number: R01AT011396

ORGANIZATION: CENTER FOR DRUG EVALUATION AND RESEARCH, NIH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/16/2022

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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