Protection of Clostridium difficile infection by metformin through its pleiotropic effects on host-bacteria-metabolite axis
Clostridium difficile (C. difficile) is the most common hospital-acquired infection- a debilitating public health threat; with a high rate of antibiotic resistance and recurrence incidences and no successful preventive and treatment options. Herein, we discovered that metformin-a safe, inexpensive, and FDA-approved antidiabetic drug, prevents C. difficile infection (CDI), by reducing microbial translocation from gut to systemic organs via promoting gut barrier functions such as increasing mucin and tight junction proteins. Metformin also beneficially modulates the gut microbiota and suppresses C. difficile's spore germination, vegetative cell growth, and toxin production, resulting in dampened CDI load. Unbiased global metabolomics analyses revealed that metformin increases the accumulation of choline in C. difficile cells, which in turn inhibits bacterial growth and toxin production.