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Fenugreek, gut microbiota, and resiliency to Western diet

Award Number: R01AT010279
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: 09/20/2018
PERIOD OF PERFORMANCE END DATE: 08/31/2024

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Fenugreek, gut microbiota, and resiliency to Western diet - Fenugreek (Trigonella foenum-graecum) is used in many parts of the world for diabetes, cardiovascular disease, and depression. While the mechanism(s) of these actions is not known, it is becoming increasingly clear that gut microbiota are key players in homeostasis and also mediate true first-pass metabolism of dietary compounds. Furthermore, the high protein and fiber content of fenugreek seeds is particularly suited to modify intestinal bacteria and offset the dysbiotic effects of high fat/low fiber Western-style diets. Indeed, data from our lab shows that fenugreek significantly alters intestinal microbial populations, and reverses key Western diet- induced changes to gut microbiota. Based on these observations, we propose the following hypothesis: Fenugreek induces physiologic resiliency via changes to intestinal microbiota Our hypothesis is based on the ability of fenugreek to offset diet-induced gut dysbiosis, and on data showing that fenugreek-shaped microbiota can replicate selected effects of fenugreek. While these data support a role for gut bacteria in beneficial responses to fenugreek, key data are needed to confirm and identify mechanisms by which fenugreek-microbiota interactions drive physiologic benefits. First, the impact of gut microbiota on the beneficial profile of fenugreek needs to be established. Further, whether fenugreek-microbiota interactions alter the gut metabolome directly via unmasking/generation of otherwise-inaccessible botanical phytochemicals; or indirectly via altered metabolism of Western diets should be resolved. Finally, identification of intestinal and blood-based metabolites that mediate fenugreek-based physiologic resiliency is needed to accelerate the translation of these findings. To meet these needs, we have devised a unique experimental approach combining conventional and germ-free mice, an adaptive microbiome transplantation paradigm, and a series of cutting-edge in silico analyses to identify microbiome-derived, fenugreek-based metabolites that drive physiologic resiliency. Specific aim 1 conventionally-housed and germ-free mice to determine how intestinal microbiota shape the beneficial effects of fenugreek. Aim 2 will use microbiome transplants to determine if specific microbiota are both necessary and sufficient for the beneficial effects of fenugreek, and will determine if fenugreek-microbiota interactions alter the gut metabolome directly via unmasking/generation of otherwise- inaccessible botanical phytochemicals; or indirectly via altered metabolism of Western diets. Aim 3 will identify the exact metabolites in blood and intestinal fractions that predict neurobehavioral and metabolic impairment using validation cohorts and state-of-the art bioinformatic tools. Identification of these metabolites, and the commensal bacteria responsible for their production, could spearhead the formulation of safe and effective strategies to preserve health in the today's modern environment. Furthermore, improved understanding how gut microbiota balance the interactions of adverse and beneficial dietary elements could be harnessed to promote physiologic resilience in all patients regardless of diet.


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: 2025 ( Subtotal = -$10,362 )
2025	2021	PENNINGTON BIOMEDICAL RESEARCH CENTER	6400 PERKINS RD	BATON ROUGE	LA	70808	EAST BATON ROUGE	USA	Research and Training in Complementary and Integrative Health	000	4	11/1/2024	NON-COMPETING CONTINUATION	-$10,362
														Subtotal = -$10,362

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	LOUISIANA STATE UNIVERSITY SYSTEM	6400 PERKINS RD	BATON ROUGE	LA	70808	EAST BATON ROUGE	USA	Research and Training in Complementary and Integrative Health	000	4	8/1/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $370,231 )
2021	2021	LOUISIANA STATE UNIVERSITY SYSTEM	6400 PERKINS RD	BATON ROUGE	LA	70808	EAST BATON ROUGE	USA	Research and Training in Complementary and Integrative Health	000	4	8/13/2021	NON-COMPETING CONTINUATION	$370,231
														Subtotal = $370,231

Issue Date FY: 2020 ( Subtotal = $369,548 )
2020	2020	LOUISIANA STATE UNIVERSITY SYSTEM	6400 PERKINS RD	BATON ROUGE	LA	70808	EAST BATON ROUGE	USA	Research and Training in Complementary and Integrative Health	001	3	8/4/2020	NON-COMPETING CONTINUATION	$369,548
2020	2019	LOUISIANA STATE UNIVERSITY SYSTEM	6400 PERKINS RD	BATON ROUGE	LA	70808	EAST BATON ROUGE	USA	Research and Training in Complementary and Integrative Health	000	2	4/22/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $369,548

Issue Date FY: 2019 ( Subtotal = $368,889 )
2019	2019	LOUISIANA STATE UNIVERSITY SYSTEM	6400 PERKINS RD	BATON ROUGE	LA	70808	EAST BATON ROUGE	USA	Research and Training in Complementary and Integrative Health	001	2	8/15/2019	NON-COMPETING CONTINUATION	$368,889
2019	2018	LOUISIANA STATE UNIVERSITY SYSTEM	6400 PERKINS RD	BATON ROUGE	LA	70808	EAST BATON ROUGE	USA	Research and Training in Complementary and Integrative Health	000	1	10/25/2018	NEW	$0
														Subtotal = $368,889

Issue Date FY: 2018 ( Subtotal = $380,253 )
2018	2018	LOUISIANA STATE UNIVERSITY SYSTEM	6400 PERKINS RD	BATON ROUGE	LA	70808	EAST BATON ROUGE	USA	Research and Training in Complementary and Integrative Health	000	1	9/20/2018	NEW	$380,253
														Subtotal = $380,253

Grand Total All Awards = $1,478,559

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Fenugreek, gut microbiota, and resiliency to Western diet

Award Number: R01AT010279

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: 09/20/2018

PERIOD OF PERFORMANCE END DATE: 08/31/2024

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