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Leveraging microbial-derived indoles to control host immune responses

Award Number: R15AI201129
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: 07/07/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2029

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Leveraging microbial-derived indoles to control host immune responses - PROJECT SUMMARY Fusobacterium spp. represent a major public health concern contributing to over 1 billion cases of oral disease worldwide, in addition to the promotion of colorectal and other cancers. Methods to control its carriage and virulence are critically needed. Microbial indoles demonstrate significant roles in controlling pathogen behavior and contributing to intestinal barrier function; however, the potentially beneficial role of indoles in controlling Fusobacterium nucleatum (Fn) virulence and host pathogen response is unknown. Preliminary data from our lab show that two indole derivatives, indole-3-aldehyde (I3A) and indole-3-carboxylic acid (I3CA), as compared to parent or other indole derivatives, have the strongest effect on reducing Fn invasion into colon cancer cells, with I3A having the strongest effect on increasing expression of genes associated with barrier function. We hypothesize that these two indoles will reduce the virulence of Fn through minimizing the ability to attach and invade human epithelial cells, increasing innate immune signaling and barrier function in a 3D culture model. Additionally, using known indole-producing genes, we will be able to computationally predict and validate other microbial pathways and species capable of producing indoles using our activity probe-based microbial profiling approach. This proposal aims to determine 1) the metabolic pathways contributing to I3A and I3CA production in the human gut microbiome using a computational gene annotation approach, 2) the identify of human gut microbes and proteins that metabolize or utilize these indoles by using a unique activity-based protein-probe approach that allows capture of indole-binding microbes in a human fecal community, and 3) the mechanisms through which these two microbial indoles are triggering innate immune signaling, increased barrier function, and contribution towards virulence and infectivity of Fn. Preliminary data presented in this application support the proposed aims and demonstrate study feasibility using tractable in vitro systems and 3D models manageable by graduate/undergraduate researcher teams with cross-training and supervision across three fields: computational, chemical, and molecular biology. Results from this research will address outstanding questions regarding indole-pathogen-host interactions and provide critical information regarding the microbes and mechanisms that can be targeted to reduce the burden of Fn on disease risk and mortality.


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 = $561,968 )
2026	2026	BAYLOR UNIVERSITY	700 S UNIVERSITY PARKS DR	WACO	TX	76706	MCLENNAN	USA	Allergy and Infectious Diseases Research	000	1	7/7/2026	NEW	$561,968
														Subtotal = $561,968

Grand Total All Awards = $561,968

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Leveraging microbial-derived indoles to control host immune responses

Award Number: R15AI201129

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: 07/07/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2029

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