Maternal omega-3 fatty acids regulate offspring obesity through persistent modulation of gut microbiota

Background: The early-life gut microbiota plays a critical role in host metabolism in later life. However, little is known about how the fatty acid profile of the maternal diet during gestation and lactation influences the development of the offspring gut microbiota and subsequent metabolic health outcomes.Results: Here, using a unique transgenic model, we report that maternal endogenous n-3 polyunsaturated fatty acid (PUFA) production during gestation or lactation significantly reduces weight gain and markers of metabolic disruption in murine offspring fed a high fat diet. These metabolic phenotypes appeared to be mediated by comprehensive restructuring of gut microbiota composition and function. Unexpectedly, reduced maternal n-3 PUFA exposure eliminated a number of commensal genera, notably Helicobacter. Interestingly, offspring metabolism and microbiota composition were more profoundly influenced by the maternal fatty acid profile during lactation than during gestation. Furthermore, the maternal fatty acid profile appeared to have a permanent effect on offspring microbiota composition and function that persisted into adulthood after life-long high fat diet feeding.Conclusions: Our data provide novel evidence that weight gain and metabolic dysfunction in adulthood is mediated by the maternal postnatal diet through profound and long-lasting restructuring of the gut microbiota. These results have important implications for understanding the interaction between modern Western diets and our symbiotic evolution with intestinal microorganisms.