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

• DOI: 10.1038/s41467-020-15545-w
• Publication Date: 2020-05-11T10:03:49Z
• Authors: Sangman M. Kim; Jennifer R. DeFazio; Sanjiv K. Hyoju; Kishan Sangani; Robert Keskey; Monika A. Krezalek; Nikolai N. Khodarev; Naseer Sangwan; Scott Christley; Katharine G. Harris; Ankit Malik; Alexander Zaborin; Romain Bouziat; Diana R. Ranoa; Mara Wiegerinck; Jordan D. Ernest; Baddr A. Shakhsheer; Irma D. Fleming; Ralph R. Weichsel...; Dionysios A. Anto...; Jack A. Gilbert; Luis B. Barreiro; Olga Zaborina; Bana Jabri; John C. Alverdy
• Keywords: Male; 0301 basic medicine; Transcription, Genetic; Science; Inbred C57BL; Article; Mice; Feces; 03 medical and health sciences; Genetic; Sepsis; Animals; Humans; Transplantation; Inflammatory and immune system; Q; Immunity; Hematology; Fecal Microbiota Transplantation; Gastrointestinal Microbiome; 3. Good health; Gastrointestinal Tract; Histone Deacetylase Inhibitors; Mice, Inbred C57BL; Infectious Diseases; Emerging Infectious Diseases; Good Health and Well Being; 5.1 Pharmaceuticals; Butyric Acid; Interferon Regulatory Factor-3; Development of treatments and therapeutic interventions; Infection; Transcription; Signal Transduction

AbstractDeath due to sepsis remains a persistent threat to critically ill patients confined to the intensive care unit and is characterized by colonization with multi-drug-resistant healthcare-associated pathogens. Here we report that sepsis in mice caused by a defined four-member pathogen community isolated from a patient with lethal sepsis is associated with the systemic suppression of key elements of the host transcriptome required for pathogen clearance and decreased butyrate expression. More specifically, these pathogens directly suppress interferon regulatory factor 3. Fecal microbiota transplant (FMT) reverses the course of otherwise lethal sepsis by enhancing pathogen clearance via the restoration of host immunity in an interferon regulatory factor 3-dependent manner. This protective effect is linked to the expansion of butyrate-producing Bacteroidetes. Taken together these results suggest that fecal microbiota transplantation may be a treatment option in sepsis associated with immunosuppression.