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Impact of the gut microbiome and diet on change in insulin homeostasis and cardiometabolic risk

Award Number: R01DK109588
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: 04/01/2017
PERIOD OF PERFORMANCE END DATE: 03/31/2025

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Impact of the gut microbiome and diet on change in insulin homeostasis and cardiometabolic risk - PROJECT SUMMARY Failure to increase insulin secretion and reduce insulin clearance to overcome tissue insulin resistance leads to the development of type 2 diabetes (T2D). Components of the insulin axis (insulin sensitivity, insulin secretion, insulin clearance) are critical to the genesis of T2D, yet the factors that account for their dysfunction and their interactions with other factors are not understood. The nutritional components of diet pass through the intestinal barrier in a complex interaction with the gut microbiota (the microbiome) to impact glucose homeostasis. Our hypothesis is that change in three insulin axis traits is associated with gut microbial composition and function, and this association is modified by dietary components (e.g., whole grains, red meat) including systemic short chain fatty acids produced by the gut microbiota. This study will assess the insulin axis, the gut microbiota and diet in a cohort of 500 non-diabetic adults (half African American, half non- Hispanic White) over 2.5 years (sampled at three time points). Specific Aim 1 will administer, at each clinic visit, a 75-g oral glucose challenge with 0, 30, 60, 120 min measurements (of insulin, glucose, and C-peptide) to determine insulin sensitivity, secretion, and clearance; habitual diet will be determined by use of a validated Food Frequency Questionnaire. Specific Aim 2 will characterize the gut microbiome for each participant by performing 16S rDNA sequencing and low-pass metagenomic sequencing on stool samples collected at all three visits. Together, these data will test the hypothesis that increased insulin resistance, impaired insulin secretion, and decreased insulin clearance (all diabetogenic changes) developing over time are associated with a reduced (at baseline) or declining (over time) abundance of short chain fatty acid-producing bacteria in the gut, in part attributable to unhealthy dietary patterns. Specific Aim 3 will utilize samples collected at the three time points to probe the functional profile of the gut microbiome by conducting deep metagenomic sequencing and assessment of circulating short chain fatty acid levels in a subset of 180 individuals with extreme changes (increase and decrease) versus those with no change in insulin axis traits, thereby identifying microbial functions that underlie change versus stability in insulin axis traits. This study has high impact, yielding knowledge that can lead to novel microbiome-based diagnostics, prevention, and/or treatment measures (e.g., specific diets; antibiotic or probiotic treatment) to reduce the public health burden of T2D.


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 = -$4,002 )
2025	2021	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	7/31/2025	NON-COMPETING CONTINUATION	-$4,002
														Subtotal = -$4,002

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2021	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	4/9/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	3/31/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $541,829 )
2021	2021	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	4/1/2021	NON-COMPETING CONTINUATION	$541,829
														Subtotal = $541,829

Issue Date FY: 2020 ( Subtotal = $583,364 )
2020	2020	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	3/12/2020	NON-COMPETING CONTINUATION	$583,364
														Subtotal = $583,364

Issue Date FY: 2019 ( Subtotal = $597,787 )
2019	2019	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	5/1/2019	NON-COMPETING CONTINUATION	$597,787
														Subtotal = $597,787

Issue Date FY: 2018 ( Subtotal = $626,334 )
2018	2018	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	4/20/2018	NON-COMPETING CONTINUATION	$563,699
2018	2018	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	4/23/2018	NON-COMPETING CONTINUATION	$62,635
														Subtotal = $626,334

Issue Date FY: 2017 ( Subtotal = $731,833 )
2017	2017	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	3/22/2017	NEW	$731,833
														Subtotal = $731,833

Grand Total All Awards = $3,077,145

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Impact of the gut microbiome and diet on change in insulin homeostasis and cardiometabolic risk

Award Number: R01DK109588

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: 04/01/2017

PERIOD OF PERFORMANCE END DATE: 03/31/2025

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