NIH grant: Defining Microbial and Host Pathways Driving Asymptomatic C. difficile Colonization Associated with Aging and High-Sugar Diets (1R01AI198579-01)

retained text

NIH grant 1R01AI198579-01: Defining Microbial and Host Pathways Driving Asymptomatic C. difficile Colonization Associated with Aging and High-Sugar Diets
Institute: {'code': 'AI', 'abbreviation': 'NIAID', 'name': 'National Institute of Allergy and Infectious Diseases', 'admin_org_id': '12500003', 'admin_funding_url': ''}. PI: James Tristan Collins. Award: $649186.
Start: 2026-06-18T00:00:00.
SUMMARY
Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated diarrhea, with rising
incidence in community settings and a growing burden of asymptomatic colonization. Asymptomatic car-
riers, particularly among the elderly and individuals consuming high-sugar diets, represent a critical but
underexplored reservoir for transmission and disease progression. This proposal introduces novel, anti-
biotic-independent mouse models demonstrating that both dietary sugar and aging independently pro-
mote asymptomatic C. difficile colonization. We hypothesize that these factors disrupt colonization re-
sistance (CR) through distinct but overlapping microbial, metabolic, and immune pathways.
In Aim 1, we will define how traditional and emerging dietary sugars alter the gut environment to permit
C. difficile colonization using in vitro bioreactors and in vivo models. Aim 2 will identify age-associated
changes in microbiota and mucosal immunity that impair CR, using longitudinal studies and fecal micro-
biota transfer. Aim 3 will functionally validate C. difficile genes upregulated during asymptomatic carriage
using CRISPR-Cas9 mutants in both sugar- and age-induced models.
This integrative, multi-omics approach will uncover the mechanisms enabling asymptomatic colonization
and identify microbial and host targets for intervention. The findings will inform microbiome-based strat-
egies to prevent CDI in vulnerable populations and shift current paradigms in CDI risk assessment and
prevention.

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