USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, 1100 Bates Avenue, Houston, TX, 77030, USA.
Vegetable and Fruit Improvement Center, Texas A&M University, College Station, TX, 77845, USA.
Sci Rep. 2018 Jul 6;8(1):10253. doi: 10.1038/s41598-018-28207-1.
Impactful dietary RNA delivery requires improving uptake and enhancing digestive stability. In mouse feeding regimes, we have demonstrated that a plant-based ribosomal RNA (rRNA), MIR2911, is more bioavailable than synthetic MIR2911 or canonical microRNAs (miRNAs). Here mutagenesis was used to discern if MIR2911 has a distinctive sequence that aids stability and uptake. Various mutations had modest impacts while one scrambled sequence displayed significantly enhanced digestive stability, serum stability, and bioavailability. To assess if small RNA (sRNA) bioavailability in mice could be improved by increasing gut permeability, various diets, genetic backgrounds and pharmacological methods were surveyed. An intraperitoneal injection of anti-CD3 antibody enhanced gut permeability which correlated with improved uptake of the digestively stable scrambled MIR2911 variant. However, the bioavailability of canonical miRNAs was not enhanced. Similarly, interleukin-10 (IL-10)-deficient mice and mice treated with aspirin displayed enhanced gut permeability that did not enhance uptake of most plant-based sRNAs. This work supports a model where dietary RNAs are vulnerable to digestion and altering gut permeability alone will not impact apparent bioavailability. We suggest that some dietary sRNA may be more digestively stable and methods to broadly increase sRNA uptake requires delivery vehicles to optimize gut and serum stability in the consumer.
有影响力的饮食 RNA 传递需要提高摄取率并增强消化稳定性。在小鼠饲养方案中，我们已经证明，基于植物的核糖体 RNA（rRNA）MIR2911 比合成的 MIR2911 或典型的 microRNAs（miRNAs）更具生物利用度。在这里，我们使用诱变来辨别 MIR2911 是否具有独特的序列来帮助其稳定性和摄取率。各种突变的影响较小，而一个乱序序列显示出显著增强的消化稳定性、血清稳定性和生物利用度。为了评估通过增加肠道通透性是否可以提高小鼠中小 RNA（sRNA）的生物利用度，我们调查了各种饮食、遗传背景和药理学方法。腹腔内注射抗 CD3 抗体增强了肠道通透性，这与消化稳定的乱序 MIR2911 变体的摄取率提高相关。然而，典型 miRNA 的生物利用度没有提高。同样，白细胞介素 10（IL-10）缺陷型小鼠和用阿司匹林治疗的小鼠表现出增强的肠道通透性，但不能增强大多数植物源性 sRNA 的摄取率。这项工作支持这样一种模型，即饮食 RNA 容易受到消化的影响，仅改变肠道通透性不会影响明显的生物利用度。我们认为，一些饮食 sRNA 可能更具消化稳定性，并且广泛增加 sRNA 摄取率的方法需要通过载体来优化消费者的肠道和血清稳定性。
