撰文 | 宋文法
俗话说，病从口入，许多疾病都与我们的饮食和生活习惯有关。很多人都有过吃坏肚子的经历，因为吃了不干净的食物而腹泻、腹痛、呕吐等，这可能就与大肠杆菌有关。
大肠杆菌（EHEC）是一种正常存在于人类和动物肠道中的细菌，但某些菌株可能会引起感染，通常通过口服感染源传播，包括吃了污染的食物或水等。大肠杆菌感染通常会导致腹泻、腹痛、呕吐和发热。而对于儿童和老人而言，感染可能会导致严重的并发症，如溶血性尿毒综合征。
色氨酸，是人体所需的必需氨基酸之一，在人体中扮演着多种重要角色，包括组成蛋白质、合成多种生物活性物质、生成血清素、褪黑素等，广泛存在于坚果、种子、全谷物和豆类中。
近日，美国康奈尔大学的研究人员在"
Nature "期刊上发表了一篇题为"
Dopamine receptor D2 confers colonization resistance via microbial metabolites
"的研究论文。
该研究显示，富含色氨酸的饮食，可以抵御肠道大肠杆菌感染，有助于预防大肠杆菌引起严重的胃痛、痉挛、发烧、肠道出血和肾衰竭。从机制上讲，色氨酸的代谢产物可以激活肠上皮中多巴胺受体D2，减少大肠杆菌在肠道上定植，让细菌良性地排出体外。
在这项研究中，研究人员通过感染了啮齿类柠檬酸杆菌的小鼠模型，分析了补充色氨酸对肠道侵害的影响，啮齿类柠檬酸杆菌与大肠杆菌非常相似，而在小鼠中，某些致病性大肠杆菌不会感染小鼠。
研究人员首先给小鼠喂食7天富含色氨酸饮食或普通饮食，并且使小鼠感染啮齿类柠檬酸杆菌，与普通饮食相比，色氨酸喂养的小鼠感染的病原体减少，结肠炎症减少。
然后，研究人员用抗生素消除了小鼠肠道中的肠道菌群，又重复了实验。结果发现，尽管小鼠吃了富含色氨酸的饮食，但它们还是被啮齿类柠檬酸杆菌。
这表明，膳食色氨酸有助于抵抗小鼠柠檬酸杆菌感染，但这种保护作用依赖于肠道菌群。
膳食色氨酸可防止小鼠柠檬酸杆菌感染
接下来，研究人员用质谱法分析了色氨酸特定代谢物，发现了最丰富的3种代谢物，当给予色氨酸饮食时，这些代谢物显著增加。同样，当单独给小鼠喂食这三种代谢物时，与色氨酸饮食小鼠具有相同的保护作用。
此外，研究人员还通过生物信息学分析来寻找哪些蛋白质（和受体）可能与色氨酸代谢物结合，发现了3种相关受体。通过人类肠道细胞系，最终确定了多巴胺受体D2（DRD2）受体，它在色氨酸代谢物存在的情况下具有抗感染保护作用。
最后，在确定完色氨酸代谢物和受体后，研究人员又分析了DRD2在人肠道上皮细胞中的下游通路，发现DRD2通路的激活，阻碍了宿主产生肌动蛋白调节蛋白的能力。而肌动蛋白是啮齿类柠檬酸杆菌与大肠杆菌附着、定殖并把毒素注入宿主细胞中必需的。
这意味着，当DRD2被激活时，肌动蛋白的行为被抑制，细菌无法在肠道扎根，随后良性地排出体外。
研究人员表示，早期研究显示，DRD2是中枢和周围神经系统中的多巴胺受体，一直不清楚在肠道中的作用，而这项新研究揭示了DRD2在肠道中的功能，表明这个受体可以在两个完全不同的领域发挥作用。
总之，结果表明，富含色氨酸的饮食可以预防致病性大肠杆菌感染，有助于预防大肠杆菌引起一系列症状。色氨酸代谢物可以激活DRD2受体，让大肠杆菌无法在肠道扎根，随后良性地排出体外。
论文链接：
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