Repurposing Metformin to Prevent Clostridioides difficile Infection in High-Risk Cardiometabolic Hosts
Description: Clostridioides difficile infection (CDI) is a major cause of severe illness, high medical costs, and repeated hospitalizations. Heart failure patients are at especially high risk and experience worse outcomes. Current treatments rely on antibiotics, which can further damage the gut microbiome and lead to recurrent infection. New preventive strategies are urgently needed for this vulnerable population. Metformin, an FDA-approved antidiabetic drug with well-established cardiovascular and heart failure benefits, has been linked in observational studies to reduced CDI risk, though causality remains unknown. Our preliminary data provide the first experimental evidence that metformin protects against CDI by lowering C. difficile colonization and toxin production, reducing gut inflammation and disease severity, and improving microbiome composition. Based upon the scientific premise of metformin’s cardiovascular benefits and its associations with CDI, we hypothesize that metformin serves as a safe, effective, and translatable strategy to prevent CDI/rCDI in high-risk HF settings. The goal of this project is to determine how metformin prevents C. difficile infection in HF-relevant settings and to clarify whether its benefits come from improving gut health and the gut microbiome. Aim 1 will test the effectiveness of metformin in preventing infection and reducing disease in models that reflect high risk heart failure conditions. Aim 2 will define how metformin shaped gut microbiota contributes to protection by studying microbiome changes and using fecal microbiota transplantation. This work will provide strong evidence for repurposing metformin as a safe, non-antibiotic strategy to prevent C. difficile infection and recurrence. The results have clear potential to improve outcomes and reduce healthcare burden for patients with heart failure and other high-risk groups.
Funder: American Heart Association
Amount: $231,000
Funding type: fellowship
Funder scheme: Career Development Award
Start date: 2026-04-01
End date: 2029-03-31
Investigators: Shaohua Wang, Shaohua Wang
Institution: Ohio University
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Funded outputs count: 0
Funder award ID: 26CDA1614202
OpenAlex ID: G8370517741