Project Grant R01AI198579

Federal Grant Award Summary

The University of Louisville's Office of Research & Innovation received a $649,186 Project Grant from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855). The award, issued on June 18, 2026, with completion by May 31, 2031, funds research to define the microbial and host pathways driving asymptomatic Clostridioides difficile (C. difficile) colonization associated with aging and high-sugar diets. The research deliverables include the development and characterization of novel, antibiotic-independent mouse models demonstrating how dietary sugar and aging independently promote asymptomatic C. difficile colonization, along with identification of the underlying microbial, metabolic, and immune mechanisms through which these factors disrupt colonization resistance.

The project employs an integrative, multi-omics research approach across three primary aims: (1) defining how traditional and emerging dietary sugars alter the gut environment to permit C. difficile colonization using in vitro bioreactors and in vivo models; (2) identifying age-associated changes in microbiota and mucosal immunity that impair colonization resistance through longitudinal studies and fecal microbiota transfer experiments; and (3) functionally validating C. difficile genes upregulated during asymptomatic carriage using CRISPR-Cas9 mutants. The research outcomes are intended to uncover mechanisms enabling asymptomatic colonization and identify microbial and host intervention targets to inform microbiome-based prevention strategies for Clostridioides difficile infection in vulnerable populations.