▎药明康德团队

很多人都有过“吃坏肚子”的经历，因为吃了不干净的东西而发生腹痛、腹泻、呕吐甚至发烧。某些产毒素的大肠杆菌是这类食源性疾病的常见肇事者，它们往往通过被污染的水果和生蔬菜、未煮熟的碎肉制品和生鲜奶进入人体，引起感染。大多数感染者能在10天内康复，但也有少数感染者，特别是幼儿和老年人，可能因为感染这类致病性大肠杆菌而发展为危急生命的疾病，例如溶血性尿毒综合征。

图片来源：123RF

最近，一项发表于《自然》的研究提出了通过饮食或药物干预来改善肠道健康、治疗胃肠道感染的新思路。

来自美国康奈尔大学的研究人员指出，补充一种常见的膳食成分——L-色氨酸（左旋色氨酸），可以帮助肠道抵御致病细菌。这项研究还进一步揭示了为什么补充L-色氨酸有这种功效：色氨酸的代谢产物会结合肠道表面的一种细胞受体，而这种受体的激活可以促使机体以良性的方式顺利将致病细菌排出，防止它们“赖在”肠道不走。

L-色氨酸是人体的必需氨基酸之一，无法自身合成，只能通过食物摄取，常见的来源包括禽肉、坚果、豆类等食物。摄入体内后，在肠道菌群的作用下，色氨酸会被分解，产生了一系列小分子代谢物。

实验中，研究人员给小鼠饲喂了添加L-色氨酸的饮食后，通过质谱分析，在肠道样本中找出了三种显著增加的代谢物。用这几种代谢物代替L-色氨酸作为饮食补充，同样可以达到保护肠道、减轻炎症的效果，避免被致病菌感染。

接下来，研究人员通过生物信息学分析，从可能与色氨酸代谢物相结合的一系列受体中找出了候选者，并通过人类肠道细胞系细胞进行验证，最终有了意外的发现：多巴胺受体DRD2是介导色氨酸代谢物抵御致病菌感染的关键受体。

研究者表示，过去人们只知道DRD2作为多巴胺受体在中枢和外周神经系统中为神经细胞传递信号，此次发现了DRD2在肠道中的新功能。

从具体的机制来说，当肠道上皮细胞中的DRD2受体被色氨酸代谢物激活，宿主细胞产生肌动蛋白调节蛋白的能力会被削弱，而致病细菌需要肌动蛋白才能把自己牢牢附着在肠道上皮细胞上，进而才能把毒素注入宿主细胞中。因此，当DRD2受体被激活，肌动蛋白不能发生聚合，也就意味着致病细菌无法在肠道“扎根”，很快会被清除出去。

值得一提的是，先前还有研究指出，L-色氨酸及其代谢物还会通过特定受体介导免疫细胞——调节性T细胞（Treg）聚集到肠道，发挥抑制炎症的作用，增强局部免疫稳态，使小鼠的炎症性肠病症状有所缓解。

这些研究一致表明，多补充L-色氨酸，有助于为肠道营造更加健康的环境。

参考资料：

[2] Tryptophan in diet, gut bacteria protect against E. coli infection. Retrieved Mar. 19, 2024 from https://medicalxpress.com/news/2024-03-tryptophan-diet-gut-bacteria-coli.html

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