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

我们的研究项目集中在膳食脂肪对肠道生态和功能的影响。具体来说，我们正在研究1）早期生活暴露于膳食脂肪对肠道微生物群组成和上皮细胞功能的影响; 2）膳食脂肪调节肠道微生物群是否介导膳食脂肪对肠道免疫的影响。 我们最近表明，母体暴露于富含n-3多不饱和脂肪酸（PUFA）或n-6 PUFA的饮食改变了大鼠肠道微生物群的组成。肠道微生物群的这种变化也与异常的免疫细胞稳态有关。与这一结果一致，我们还发现，早期生活暴露于向日葵籽油（富含n-6 PUFA）会导致小鼠肠道微生物群发生显着变化。 在拟议的研究中，我们将扩大这项工作。我们将比较含有高，中，低n-6/n-3 PUFA比例的饮食的影响。我们的短期目标是通过深入分析肠道微生物群组成来确定早期生活暴露于膳食脂肪（向日葵籽油和鱼油）对肠道生态的影响。重要的是，我们将确定肠道微生物群是否在膳食脂肪调节的粘膜免疫中起关键作用。最后但并非最不重要的是，我们将研究生命早期暴露于膳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生命早期的膳食脂肪摄入如何塑造肠道微生物群和上皮功能，以及它们如何与晚年肠道免疫力的变化相关。

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.