Metformin reduces Clostridium difficile infection

Abstract

Clostridium difficile (C. difficile) is the most common pathogen causing hospital acquired infections, linked with dramatic abnormal changes in gut microbiome. Antibiotic resistance is common in C. difficile and currently invasive procedures like fecal microbiota transplantation is only viable option, which also do not stop recurrence incidences. Thus, discovering non-invasive, safe, inexpensive and clinically adoptable strategies are needed. Here, we demonstrated that metformin- a safe, inexpensive and FDA approved antidiabetic drug, showed growth inhibitory activity against the C. difficile. We show that metformin reduces vegetative cell growth of C. difficile in-vitro, as well as ex-vivo in human microbiome culture system. Interestingly, metformin beneficially modified human gut microbiome by decreasing C. difficile growth while increasing the growth of non-pathogenic Clostridium strains. In addition, metformin inhibit colonization of C. difficile in mice and significantly reduces infection clinical score. Metformin reduced C. difficile colonization more than 10 times in caecum and 100 times in colon; and it also reduced bacterial translocation from gut to spleen, liver and mesenteric lymph nodes. Overall, our results demonstrated that metformin reduces the C. difficile infection and can be re-purposed for prevention and treatment of C. difficile infections in clinical settings.