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Elucidating the consequences of dietary sugar consumption on the gut microbiota

Award Number: R01DK132711
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2023
PERIOD OF PERFORMANCE END DATE: 02/28/2027

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Elucidating the consequences of dietary sugar consumption on the gut microbiota - Project Summary The gut microbiota is a critical determinant of human health and development. Diets rich in the refined sugars glucose and fructose can modulate gut microbial abundance and metabolism thereby increasing disease susceptibility. However, the mechanisms governing microbial responses to dietary sugar in the gut remain poorly understood. We have demonstrated that host dietary sugar consumption silences expression of a colonization factor called Roc in Bacteroides thetaiotaomicron, an abundant gut bacterium associated with lean, healthy individuals. We determined that a conserved transcription factor is necessary to synthesize Roc and regulates additional bacterial factors that mediate critical host-microbial interactions, including an immunomodulatory protein and fucose utilization genes. We hypothesize that the activity of this transcription factor is governed by a putative intracellular metabolite that is differentially synthesized according to host diet composition and dramatically reduced upon sugar-rich diet consumption. We have identified critical molecular players governing the activity of this transcription factor and propose to 1.) elucidate the mechanisms governing its activation, 2.) determine how dietary sugar consumption silences its activity, and 3.) characterize the consequences of host sugar-rich diet consumption on microbial product synthesis in vivo. We believe that this work will reveal a conserved pathway that is disrupted by host sugar consumption resulting in aberrant gut microbial activities. Furthermore, this work has uncovered a molecular target for modulation of microbial abundance and metabolism in the host and can be exploited for rational manipulation of the gut microbiota to treat diseases.


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 = $562,589 )
2026	2026	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	2/11/2026	NON-COMPETING CONTINUATION	$562,589
														Subtotal = $562,589

Issue Date FY: 2025 ( Subtotal = $506,330 )
2025	2025	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	2/28/2025	NON-COMPETING CONTINUATION	$506,330
														Subtotal = $506,330

Issue Date FY: 2024 ( Subtotal = $540,085 )
2024	2024	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	5/15/2024	NON-COMPETING CONTINUATION	$33,755
2024	2024	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	1/30/2024	NON-COMPETING CONTINUATION	$506,330
														Subtotal = $540,085

Issue Date FY: 2023 ( Subtotal = $590,990 )
2023	2023	PENNSYLVANIA STATE UNIVERSITY	500 UNIVERSITY DRIVE	HERSHEY	PA	17033	DAUPHIN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	4/20/2023	NEW	$590,990
														Subtotal = $590,990

Grand Total All Awards = $2,199,994

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Elucidating the consequences of dietary sugar consumption on the gut microbiota

Award Number: R01DK132711

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2023

PERIOD OF PERFORMANCE END DATE: 02/28/2027

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