A reproducible enteric phage community improves blood glucose regulation in an obesity mouse model

Abstract Metabolic syndrome encompasses amongst other conditions like obesity, type-2 diabetes, and non-alcoholic fatty liver disease, that all are associated with gut microbiome (GM) dysbiosis. Fecal microbiota transplantation (FMT) has been explored to treat metabolic syndrome by restoring the GM. FMT is generally safe, but motivated by case-reports, accidental transfer of pathogenic bacteria remains a concern. Fecal virome transplantation (FVT, sterile-filtrated feces) from lean donors has shown promise in alleviating metabolic effects of a high-fat diet. FVT has the advantage over FMT that mainly bacteriophages are transferred but still carries the risk of eukaryotic viral infections. To address this, modified FVTs were compared with unmodified FVT and saline in a mouse model of diet-induced obesity. Unmodified-FVT improved liver pathology and reduced adipose inflammation, while “eukaryotic-virus-free” FVT enhanced blood glucose clearance. GM analysis suggested bacteriophage-mediated GM modulation had influenced these outcomes. This may pave the way for developing bacteriophage-based therapies for metabolic syndrome through GM restoration.