Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity

Death due to sepsis remains a persistent threat to critically ill patients and is characterized by colonization with multidrug-resistant healthcare-associated pathogens. In a mouse model, sepsis caused by a defined four-member pathogen community isolated from a patient with lethal sepsis is associated with systemic suppression of host transcripts necessary for pathogen clearance and decreased butyrate. These pathogens directly suppress interferon regulatory factor 3 (IRF3). Fecal microbiota transplant (FMT) reverses otherwise lethal sepsis by enhancing pathogen clearance via restoration of host immunity in an IRF3-dependent manner. Protection is linked to expansion of butyrate-producing Bacteroidetes. These results suggest that fecal microbiota transplantation may be a treatment option in sepsis associated with immunosuppression.