<br>切换小鼠肠类的极性会影响上皮细胞与甘草根异戊二烯化酚类的相互作用,Food & Function

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切换小鼠肠类的极性会影响上皮细胞与甘草根异戊二烯化酚类的相互作用
Food & Function ( IF 5.1 ) Pub Date : 2023-12-12 , DOI: 10.1039/d3fo02961a
Sarah van Dinteren _{1,

2} , Carla Araya-Cloutier ₂ , Edyta Robaczewska ₁ , Mellody den Otter ₁ , Renger Witkamp ₁ , Jean-Paul Vincken ₂ , Jocelijn Meijerink ₁

Affiliation

由于顶端上皮面向内部，3D 小肠类器官（肠样）模型用于评估食品（相关）化合物的影响的效用受到限制。为了克服这一限制，我们开发了一种新型的小鼠 3D 顶端出肠模型，该模型允许顶端暴露。使用该模型，我们评估了接触光甘草定后对肠类肠上皮的影响（包括细胞毒性、细胞活力和生物转化），光甘草定是一种来自甘草根（光果甘草）的具有抗菌特性的异戊二烯化次级代谢产物。与传统的顶端内肠相比，顶端外肠对光甘草定暴露的敏感性低五倍，获得的细胞毒性分别为 1.5 mM 和 0.31 mM。顶端出肠样显示出富含岩藻糖的粘液的管腔/顶端层，这可能有助于防止光甘草定的潜在细胞毒性。此外，在顶端肠内，测定了甘草查尔酮 A、甘草香豆素和光甘草定（分别来自常用的G. infata 、 G. uralensis和G. glabra ）的物种特异性异戊二烯化酚类物质的细胞毒性 IC ₅₀值。两种肠样模型的不同之处在于其功能性第二阶段生物转化能力，其中光甘草定被转化为葡萄糖醛酸和硫酸盐结合物。最后，我们的结果表明，在先前报道的针对多种革兰氏阳性菌的最低抑制浓度（MIC）下，异戊二烯化酚类在小鼠肠类中没有表现出细胞毒性。总而言之，我们表明，与传统的肠类相比，顶端出的肠类提供了更好的胃肠道模拟，因此是研究食物（相关）化合物的效果的优越模型。这项工作表明，具有良好抗菌活性的异戊烯化酚类在其 MIC 的胃肠道中没有显示出有害影响，因此可能为控制有害微生物的生长提供新的视角。

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Switching the polarity of mouse enteroids affects the epithelial interplay with prenylated phenolics from licorice (Glycyrrhiza) roots

The utility of 3D-small intestinal organoid (enteroid) models for evaluating effects of e.g. food (related) compounds is limited due to the apical epithelium facing the interior. To overcome this limitation, we developed a novel 3D-apical-out enteroid model for mice, which allows apical exposure. Using this model, we evaluated the effects on the enteroids’ intestinal epithelium (including cytotoxicity, cell viability, and biotransformation) after exposure to glabridin, a prenylated secondary metabolite with antimicrobial properties from licorice roots (Glycyrrhiza glabra). Apical-out enteroids were five times less sensitive to glabridin exposure compared to conventional apical-in enteroids, with obtained cytotoxicities of 1.5 mM and 0.31 mM, respectively. Apical-out enteroids showed a luminal/apical layer of fucose rich mucus, which may contribute to the protection against potential cytotoxicity of glabridin. Furthermore, in apical-in enteroids IC₅₀ values for cytotoxicity were determined for licochalcone A, glycycoumarin, and glabridin, the species-specific prenylated phenolics from the commonly used G. inflata, G. uralensis, and G. glabra, respectively. Both enteroid models differed in their functional phase II biotransformation capacity, where glabridin was transformed to glucuronide- and sulfate-conjugates. Lastly, our results indicate that the prenylated phenolics do not show cytotoxicity in mouse enteroids at previously reported minimum inhibitory concentrations (MICs) against a diverse set of Gram positive bacteria. Altogether, we show that apical-out enteroids provide a better mimic of the gastrointestinal tract compared to conventional enteroids and are consequently a superior model to study effects of food (related) compounds. This work revealed that prenylated phenolics with promising antibacterial activity show no harmful effects in the GI-tract at their MICs and therefore may offer a new perspective to control unwanted microbial growth.

更新日期：2023-12-12

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