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Sex related differences in Brain Gut Microbiome Interactions in Irritable Bowel Syndrome

Award Number: U54DK123755
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2020
PERIOD OF PERFORMANCE END DATE: 06/30/2031

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Sex related differences in Brain Gut Microbiome Interactions in Irritable Bowel Syndrome - ABSTRACT | OVERALL This SCORE grant integrates three Projects, all centered around understanding and characterizing sex differences in brain gut microbiome (BGM) interactions related to irritable bowel syndrome (IBS) and its comorbid symptoms, which disproportionately affect females. Our overall hypothesis is that higher chronic stress reactivity (SR) predisposes IBS patients to having comorbid symptoms in a sex-dependent manner and is characterized by a distinct brain signature, alterations in autonomic nervous system (ANS) activity and distinct gut microbial composition and metabolites which modulate sensory neuronal responses. These sex-specific mechanisms underlie the increased prevalence and severity of comorbid symptoms in females with IBS compared to males. We will address these hypotheses in three synergistic Projects, led by investigators with extensive experience in sex as a biological variable (SABV) research, that will be assisted by an Analytical LCMS Core, Leadership Administrative Core, and a Career Enhancement Core. Project 1 will measure clinical traits, susceptibility genes, environmental stress, and peripheral biologic measures of SR that contribute to sex differences in IBS severity and comorbid symptoms using both large biomedical databases and newly collected data from males and females with IBS and healthy controls. As non-invasive vagal nerve stimulation (nVNS) has been shown to have therapeutic effects in IBS as well as several co-morbid conditions, Project 1 will also test sex differences in the impact of nVNS on IBS and comorbid symptom severity and biological measures of SR in IBS participants in a randomized clinical trial (RCT). Project 2 will define brain signatures associated with high SR and increased comorbidity in IBS, and test sex specific aspects of this phenotype using both a large biomedical database and advanced neuroimaging on males and females with IBS recruited for Project 1, including those in the nVNS clinical trial. Project 3 uses experimental mouse models to define effects of sex-biased microbial metabolites on dorsal root (DRG) and vagal neuron activity in mice and further evaluate effects of host biological sex on DRG and vagal neuronal responses to microbial metabolites. The Project also aims to determine how microbiome- responsive DRG and vagal neurons impact visceral sensitivity and anxiety-like behavior in a sex-dependent manner. Together, this proposal aims to enhance our understanding of why females with IBS are more predisposed to comorbid symptoms, while there may be a protective effect in males. The presence of comorbid symptoms in IBS is more complex and poses challenges in effectively managing multiple symptoms, which are often more resistant to standard therapies. Effective treatment for IBS with comorbid symptoms requires addressing both gastrointestinal and extraintestinal symptoms, highlighting the need for a comprehensive approach to manage their overall health more effectively. These studies will advance our understanding of sex- specific pathophysiologic mechanisms in IBS and its comorbidities. The anticipated findings could lead to personalized, multi-system interventions to improve outcomes for IBS patients with comorbidities.


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: 2027 ( Subtotal = $3 )
2027	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	10/14/2026	NON-COMPETING CONTINUATION	$3
														Subtotal = $3

Issue Date FY: 2026 ( Subtotal = $1,499,714 )
2026	2026	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	6	9/17/2026	COMPETING CONTINUATION	$1,499,717
2026	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	1/7/2026	NON-COMPETING CONTINUATION	$0
2026	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	8/26/2026	NON-COMPETING CONTINUATION	-$3
														Subtotal = $1,499,714

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	4/18/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $1,547,473 )
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	7/25/2024	NON-COMPETING CONTINUATION	$1,547,473
2024	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	12/29/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,547,473

Issue Date FY: 2023 ( Subtotal = $1,246,739 )
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	8/9/2023	NON-COMPETING CONTINUATION	$1,246,739
														Subtotal = $1,246,739

Issue Date FY: 2022 ( Subtotal = $1,548,022 )
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	3	8/22/2022	NON-COMPETING CONTINUATION	$1,548,022
2022	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	3/10/2022	NON-COMPETING CONTINUATION	$0
2022	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	8/19/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,548,022

Issue Date FY: 2021 ( Subtotal = $1,539,730 )
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	8/3/2021	NON-COMPETING CONTINUATION	$1,539,730
2021	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	12/17/2020	NEW	$0
														Subtotal = $1,539,730

Issue Date FY: 2020 ( Subtotal = $1,584,406 )
2020	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	4/23/2020	NEW	$1,584,406
														Subtotal = $1,584,406

Grand Total All Awards = $8,966,087

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Sex related differences in Brain Gut Microbiome Interactions in Irritable Bowel Syndrome

Award Number: U54DK123755

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 05/01/2020

PERIOD OF PERFORMANCE END DATE: 06/30/2031

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