Project Grant R15AI201129

Grant Award Summary

Baylor University received a $561,968 Project Grant from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855), awarded July 7, 2026, with a completion date of June 30, 2029. The research project investigates the use of microbial-derived indole compounds—specifically indole-3-aldehyde (I3A) and indole-3-carboxylic acid (I3CA)—to control the virulence of Fusobacterium nucleatum (FN), a pathogenic bacterium associated with oral disease, colorectal cancer, and other malignancies affecting over 1 billion individuals globally. The project deliverables include identifying the metabolic pathways responsible for I3A and I3CA production in the human gut microbiome using computational gene annotation, characterizing the human gut microbes and proteins that metabolize or utilize these indoles through activity-based protein-probe approaches, and elucidating the immunological mechanisms through which these indoles trigger innate immune signaling and enhance intestinal barrier function to reduce FN virulence.

The research employs a three-pronged investigative approach combining computational biology, microbial profiling using activity probes, and in vitro 3D culture models to validate preliminary findings demonstrating that I3A and I3CA more effectively reduce FN invasion into colon cancer cells compared to other indole derivatives. By identifying indole-producing metabolic genes and validating complementary microbial species capable of generating these compounds, the project aims to establish a foundation for microbiome-based therapeutic strategies to mitigate FN-associated disease burden through enhancement of host immune responses and epithelial barrier integrity.