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

背景：生命早期的肠道菌群对宿主晚年的代谢功能具有关键调控作用。然而，目前对于母体在妊娠与哺乳期间的膳食脂肪酸谱如何影响子代肠道菌群发育及其后续代谢健康结局，仍知之甚少。
结果：本研究通过独特的转基因模型证实，母体在妊娠或哺乳阶段内源性合成的n-3多不饱和脂肪酸（n-3 polyunsaturated fatty acid, PUFA），可显著降低高脂饮食饲喂的小鼠子代的体重增长与代谢紊乱标志物水平。上述代谢表型似乎是通过全面重塑肠道菌群的组成与功能所介导的。出乎意料的是，母体n-3 PUFA暴露不足会消除多种共生菌属，其中尤以螺杆菌属（Helicobacter）最为突出。值得关注的是，相较于妊娠阶段，母体膳食脂肪酸谱对子代代谢与菌群组成的影响更为深远。此外，母体膳食脂肪酸谱对子代菌群组成与功能的影响具有永久性，即使在子代终身饲喂高脂饮食后，该影响仍持续至成年阶段。
结论：本研究数据提供了新的证据，表明成年个体的体重增长与代谢功能障碍，可通过母体产后膳食对肠道菌群进行深刻且持久的重塑而介导。上述结果对于理解现代西式膳食与我们同肠道微生物的共生演化之间的相互作用，具有重要的借鉴意义。