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Immune interactions with commensal microbes in early life

Award Number: R01AI173220
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: 11/02/2022
PERIOD OF PERFORMANCE END DATE: 10/31/2027

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Immune interactions with commensal microbes in early life - Project Summary/Abstract Events in early life, particularly those altering the gut microbiota and immune development, can have an important role in determining future risk of immune related disorders. For example, it has been reported that the how substances are encountered by the immune system, the timing of feeding practices, hygiene, and the use of antibiotics, in early life can modify the risk of immune driven disorders later in life. A common theme amongst many of these studies is that these risk factors likely affect the developing microbiota. However, the biologic basis for how early life microbial changes can affect the risk of immune disorders later in life is incompletely understood. Previous data from our laboratories have suggested that during this preweaning period, specific live gut bacteria are selectively delivered to the immune system and that interaction of these live bacteria with cellular immune populations locally in the colonic lamina propria or in distant lymphoid tissues establishes a durable (life- long) and balanced immune system. In preliminary studies, we observed substantial variance in the amount of bacterial translocation in this preweaning period, which was corroborated with studies of antigen-specific T cell responses to a translocating bacterial spp. We therefore hypothesize that the magnitude and quality of the immune response to these translocating bacteria species during the preweaning period is a stochastic event during normal ontogeny which represents an important variable in determining whether an individual establishes a balanced immune system and prevents immune mediated pathologies in later life. However, the nature of these translocating bacteria and methods to quantify the antigen-specific responses to these bacteria remain a gap in our knowledge. We will address this question by identifying and characterizing how the translocating bacteria are encountered by the immune system (Aim 1) and generate reagents to track bacterial antigen presentation via T cell responses in vivo (Aim 2). We will use these reagents to integrate the immune response over the preweaning period to translocating bacterial spp. during physiologic development and correlate it with intestinal immune challenges including infection and experimental colitis in later life (Aim 3). If successful, this project may reveal that preweaning translocation is an important stochastic developmental variable involved in generating intestinal immune health and homeostasis.


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 = $706,668 )
2026	2026	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	4	12/8/2025	NON-COMPETING CONTINUATION	$706,668
														Subtotal = $706,668

Issue Date FY: 2025 ( Subtotal = $685,469 )
2025	2025	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	3	1/14/2025	NON-COMPETING CONTINUATION	$685,469
														Subtotal = $685,469

Issue Date FY: 2024 ( Subtotal = $706,668 )
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	2	10/24/2023	NON-COMPETING CONTINUATION	$636,001
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	001	2	5/13/2024	NON-COMPETING CONTINUATION	$70,667
														Subtotal = $706,668

Issue Date FY: 2023 ( Subtotal = $715,237 )
2023	2023	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	1	11/2/2022	NEW	$715,237
														Subtotal = $715,237

Grand Total All Awards = $2,814,042

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Immune interactions with commensal microbes in early life

Award Number: R01AI173220

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: 11/02/2022

PERIOD OF PERFORMANCE END DATE: 10/31/2027

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