Flavones represent a class of polyphenols that are found in many plant-derived food sources. Herein, we provide evidence that the anti-inflammatory and antiproliferative effect of the flavone apigenin relies on the regulation of the gut microbiota by the NOD-like receptor family pyrin domain containing 6 (Nlrp6). When challenged by dextran sulfate sodium (DSS) in drinking water, mice were protected against colitis upon cohousing with apigenin-treated animals. In contrast, the protective effect was lost in the absence of Nlrp6. Sequencing of the 16S ribosomal RNA gene revealed a shift in the composition of the gut microbiota in apigenin-treated mice that was not observed in the absence of Nlrp6. Equally important, we find that the antiproliferative effect of apigenin was dominantly transmitted after cohousing, while being compromised in Nlrp6-deficient mice. In contrast, the symptoms of colitis were alleviated upon apigenin administration even in the absence of either caspase-1/11 or Asc. Collectively, these data indicate that apigenin modulated an inflammasome-independent mechanism by which Nlrp6 reprograms the gut microbiota for protecting mice against colitis. Our study highlights a modulation of the Nlrp6 signaling pathway by a prominent constituent of the human diet that may point toward improved ways to treat inflammatory bowel diseases.

中文翻译：

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膳食黄酮通过独立于炎性体激活的 NLRP6 信号传导提供针对结肠炎的传染性保护。

黄酮代表一类多酚，存在于许多植物来源的食物来源中。在此，我们提供证据表明黄酮芹菜素的抗炎和抗增殖作用依赖于含有 NOD 样受体家族 pyrin 结构域 6 (Nlrp6) 对肠道微生物群的调节。当在饮用水中受到葡聚糖硫酸钠 (DSS) 的挑战时，小鼠在与芹菜素处理的动物同住后免受结肠炎的侵害。相反，在没有 Nlrp6 的情况下，保护作用就消失了。16S 核糖体 RNA 基因的测序揭示了在芹菜素处理的小鼠中肠道微生物群的组成发生了变化，这在没有 Nlrp6 的情况下没有观察到。同样重要的是，我们发现芹菜素的抗增殖作用主要在同居后传递，同时在 Nlrp6 缺陷小鼠中受到损害。相反，即使在没有 caspase-1/11 或 Asc 的情况下，服用芹菜素后结肠炎的症状也会得到缓解。总的来说，这些数据表明芹菜素调节了一种独立于炎性体的机制，Nlrp6 通过该机制重新编程肠道微生物群以保护小鼠免受结肠炎的侵害。我们的研究强调了人类饮食中重要成分对 Nlrp6 信号通路的调节，这可能指向治疗炎症性肠病的改进方法。这些数据表明，芹菜素调节了一种独立于炎症小体的机制，Nlrp6 通过该机制重新编程肠道微生物群以保护小鼠免受结肠炎的侵害。我们的研究强调了人类饮食中重要成分对 Nlrp6 信号通路的调节，这可能指向治疗炎症性肠病的改进方法。这些数据表明，芹菜素调节了一种独立于炎症小体的机制，Nlrp6 通过该机制重新编程肠道微生物群以保护小鼠免受结肠炎的侵害。我们的研究强调了人类饮食中重要成分对 Nlrp6 信号通路的调节，这可能指向治疗炎症性肠病的改进方法。