The effects of early life exposure to dietary fat on intestinal ecology and function

我们的研究项目集中在饮食脂肪对肠道生态和功能的影响。具体地说，我们正在研究1)生命早期接触饮食脂肪对肠道微生物区系组成和上皮细胞功能的影响；2)饮食脂肪是否调节肠道微生物区系介导饮食脂肪对肠道免疫的影响。 我们最近发现，母亲摄入富含n-3多不饱和脂肪酸(PUFA)或n-6多不饱和脂肪酸(PUFA)的饮食会改变大鼠肠道微生物区系的组成。肠道微生物区系的这种变化也与免疫细胞稳态的异常有关。与这一结果一致的是，我们还发现，生命早期接触葵花油(富含n-6多不饱和脂肪酸)会导致小鼠肠道微生物区系发生显著变化。 在拟议的研究中，我们将扩展这项工作。我们将比较高、中、低n-6/n-3多不饱和脂肪酸比例的饮食效果。我们的短期目标是通过深入分析肠道微生物区系组成，确定早期接触膳食脂肪(葵花籽油和鱼油)对肠道生态的影响。重要的是，我们将确定肠道微生物区系在饮食脂肪调节粘膜免疫中是否发挥关键作用。最后但同样重要的是，我们将检查早期接触饮食脂肪对肠道粘液层完整性和抗菌反应的影响。这项拟议的研究将进一步深入了解早期饮食脂肪摄入如何塑造肠道微生物区系和上皮功能，以及它们如何与以后肠道免疫的变化相关联。

Our research program focuses on the effects of dietary fat on the intestinal ecology and function. Specifically, we are studying 1) the effect of early life exposure to dietary fat on the intestinal microbiota composition and epithelial cell function; 2) whether dietary fat modulated intestinal microbiota mediates the effects of dietary fat on intestinal immunity. We have recently shown that maternal exposure to diet rich in either n-3 polyunsaturated fatty acid (PUFA) or n-6 PUFA altered the intestinal microbiota composition in rats. Such changes in intestinal microbiota are also associated with aberrant immune cell homeostasis. Consistent with this result, we also found that early life exposure to sunflower oil (rich in n-6 PUFA) induces significant changes in the intestinal microbiota in mice. In the proposed studies, we will extend this work. We will compare the effects of diets that contain high, medium and low ratios of n-6/n-3 PUFA. Our short-term goal is to define the effect of early life exposure to dietary fat (sunflower oil and fish oil) on intestinal ecology by in-depth analysis of the intestinal microbiota composition. Importantly, we will determine whether the intestinal microbiota plays a key role in dietary fat modulated mucosal immunity. Last but not least, we will examine the impact of early life exposure to dietary fat on the intestinal mucus layer integrity and antimicrobial responses. The proposed research will provide further insight into how dietary fat intake in early life shapes the intestinal microbiota and epithelial function and how they are associated with changes in intestinal immunity in later life.