The Transplantation of ω3 PUFA-Altered Gut Microbiota of Fat-1 Mice to Wild-Type Littermates Prevents Obesity and Associated Metabolic Disorders

Abstract : Altering the gut microbiome may be beneficial to the host, and it recently arose as a promising strategy to manage obesity. Here, we investigated the relative contribution of ω3 polyunsaturated fatty acid (PUFA)-mediated alterations in the microbiota to metabolic parameter changes in mice. Four groups were compared: male fat-1 transgenic mice (with constitutive production of ω3 PUFAs) and male WT littermates fed either an obesogenic (high fat/high sucrose, HFHS) or a control diet. Unlike WT mice, HFHS-fed fat-1 mice were protected against obesity, glucose intolerance and hepatic steatosis. Unlike WT mice, fat-1 mice maintained a normal barrier function, resulting in a significantly lower metabolic endotoxemia. Fat-1 mice displayed greater phylogenic diversity in the cecum, and fecal microbiota transplantation from fat-1 to WT mice was able to reverse weight gain and to normalize glucose tolerance and intestinal permeability. We concluded that the ω3 fatty acid-mediated alteration of gut microbiota contributed to the prevention of metabolic syndrome in fat-1 mice. It occurred independently of changes in PUFA content of host tissues, and may represent a promising strategy to prevent metabolic disease and to preserve a lean phenotype.