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Impact of L. plantarum 299v supplementation on endothelial function and inflammation in humans with type 2 diabetes

Award Number: K24HL152143
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 12/10/2020
PERIOD OF PERFORMANCE END DATE: 11/30/2025

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Impact of L. plantarum 299v supplementation on endothelial function and inflammation in humans with type 2 diabetes - This mid-career development award application is designed to provide critical protected time for the applicant to increase and improve his mentoring activities along with further developing his research program in clinically oriented translational research in vascular biology and endothelial function. During his 12+ years as a faculty member, the applicant has served as research mentor for 17 post-doctoral mentees, including 10 physician- scientists. Nearly 90% percent of the applicant's mentees engaged in patient-oriented research, nearly 50% percent are women, and 82% have remained in academic medicine settings. As part of this program, the applicant will create a more detailed and structured mentorship program for his trainees who are interested in careers in patient-oriented clinical/translational research in vascular biology and physiology. This K24 application is scientifically centered on determining the vascular and inflammatory impact of supplementation of humans with type 2 diabetes (T2DM) with the probiotic Lactobacillus plantarum 299v (Lp299v). This proposal represents a natural outgrowth of the applicant's current work. Despite aggressive traditional risk factor modification and glycemic control efforts with even the most recent glycemic control agents with favorable cardiovascular profiles, atherosclerotic vascular diseases and microvascular disease continue to disproportionately impact individuals with diabetes mellitus (DM). Vascular disease in T2DM begins with the development of vascular endothelial dysfunction. The applicant's group recently reported that once daily supplementation with Lp299v results in improved endothelial function and reduced systemic vascular inflammation in men with stable coronary artery disease. This was the first report of a probiotic supplement having a favorable impact on vascular endothelial function in humans. While this data supports the concept that Lp299v improves vascular endothelial function and reduces systemic inflammation, only three individuals in the pilot study had T2DM. Whether the favorable effects of Lp299v supplementation extend to humans with T2DM remains uncertain. Equipose regarding impact of Lp299v supplementation in human T2DM is further supported by the known significant differences in the composition and metabolism of the gut microbiota of humans with T2DM suggesting the interaction of T2DM gut microbiota with Lp299v may significantly differ compared to those without diabetes. The applicant's preliminary data suggest Lp299v's favorable impact on endothelium-dependent vasodilation and vascular inflammation may be magnified in individuals with T2DM. We will test the hypothesis that Lp299v supplementation improves endothelium-dependent vasodilation and microvascular function, reduces inflammation, and improves insulin sensitivity in humans with T2DM in the setting of a randomized, double-blind, placebo-controlled crossover clinical trial. The proposed studies will both advance our knowledge about a novel method for reducing vascular risk in T2DM through a gut microbiota-targeted intervention and provide an outstanding framework for mentoring the next generation of researchers in vascular-centered patient-oriented research.


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 = $114,463 )
2025	2025	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Cardiovascular Diseases Research	000	5	11/29/2024	NON-COMPETING CONTINUATION	$114,463
														Subtotal = $114,463

Issue Date FY: 2024 ( Subtotal = $114,463 )
2024	2024	THE MEDICAL COLLEGE OF WISCONSIN, INC.	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Cardiovascular Diseases Research	000	4	11/29/2023	NON-COMPETING CONTINUATION	$114,463
														Subtotal = $114,463

Issue Date FY: 2023 ( Subtotal = $114,463 )
2023	2023	MEDICAL COLLEGE OF WISCONSIN, INC., THE	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Cardiovascular Diseases Research	000	3	12/19/2022	NON-COMPETING CONTINUATION	$114,463
														Subtotal = $114,463

Issue Date FY: 2022 ( Subtotal = $114,463 )
2022	2022	MEDICAL COLLEGE OF WISCONSIN, INC., THE	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Cardiovascular Diseases Research	000	2	12/2/2021	NON-COMPETING CONTINUATION	$114,463
														Subtotal = $114,463

Issue Date FY: 2021 ( Subtotal = $114,463 )
2021	2021	MEDICAL COLLEGE OF WISCONSIN, INC., THE	8701 WATERTOWN PLANK RD	MILWAUKEE	WI	53226	MILWAUKEE	USA	Cardiovascular Diseases Research	000	1	12/7/2020	NEW	$114,463
														Subtotal = $114,463

Grand Total All Awards = $572,315

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Impact of L. plantarum 299v supplementation on endothelial function and inflammation in humans with type 2 diabetes

Award Number: K24HL152143

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 12/10/2020

PERIOD OF PERFORMANCE END DATE: 11/30/2025

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