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Development of humanized microbiota mouse models of ME/CFS

Award Number: R21AI183042
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/07/2024
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Development of humanized microbiota mouse models of ME/CFS - Project Summary/Abstract Our preliminary data, as well as our previous published studies, show that ME/CFS cases have alterations in gastrointestinal mucosal immunity and mitochondrial homeostasis. Several other studies have described significant alterations in the composition of the gut microbiome in ME/CFS cases, when compared to age and gender-matched controls, potentially implicating a pathological role for a dysbiotic microbiota in the progression of ME/CFS through the gut-microbiota-brain axis. We hypothesize that by conducting a fecal microbiota transplantation (FMT) with stool from ME/CFS cases into mice that are engrafted with a functional human immune system, we can develop an animal model that will replicate ME/CFS-associated pathology. We further hypothesize that this model can be used to conduct ME/CFS research that is not practical or possible when working with human subjects. In Specific Aim 1, we will characterize and transplant stool from ME/CFS cases and healthy controls into common C57BL/6J laboratory mice, which have a normal murine immune system, as well as mice that are engrafted with a functional human immune system. We will then evaluate these mice for exercise intolerance, neurocognitive dysfunction, and sleep disturbances; behavioral alterations consistent with those observed in human cases. In Aim 2, we will pathologically evaluate these mice to identify changes in the gut and the brain that potentially implicate the altered microbiota in ME/CFS pathophysiology. These studies will lay the foundation for a larger research focus to identify ways to target the gut-microbiota brain axis in the prevention and treatment of ME/CFS. ME/CFS is a multisystemic, debilitating, and neglected illness for which no accepted efficacious treatments are currently available. Population-based epidemiologic studies suggest that ME/CFS may affect as many as 2.5 million people in the United States alone. Moreover, ME/CFS produces an annual economic burden of at least $17 billion 4. Although ME/CFS represents a serious public health concern, after almost four decades of research, the pathophysiology of this illness is still largely unknown.


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 = $0 )
2026	2025	BOARD OF REGENTS OF NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Allergy and Infectious Diseases Research	000	2	1/9/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $182,100 )
2025	2025	BOARD OF REGENTS OF THE NEVADA SYSTEM OF HIGHER ED	1664 N VIRGINIA ST # 285	RENO	NV	89557	WASHOE	USA	Allergy and Infectious Diseases Research	000	2	4/11/2025	NON-COMPETING CONTINUATION	$182,100
														Subtotal = $182,100

Issue Date FY: 2024 ( Subtotal = $218,850 )
2024	2024	BOARD OF REGENTS OF THE NEVADA SYSTEM OF HIGHER ED	1664 N VIRGINIA ST # 285	RENO	NV	89557	WASHOE	USA	Allergy and Infectious Diseases Research	001	1	9/11/2024	NEW	$21,885
2024	2024	BOARD OF REGENTS OF THE NEVADA SYSTEM OF HIGHER ED	1664 N VIRGINIA ST # 285	RENO	NV	89557	WASHOE	USA	Allergy and Infectious Diseases Research	000	1	5/7/2024	NEW	$196,965
														Subtotal = $218,850

Grand Total All Awards = $400,950

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Development of humanized microbiota mouse models of ME/CFS

Award Number: R21AI183042

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/07/2024

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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