多组学联用揭示花粉过敏基于肠道菌的新机制

工程（英文） ›› 2022, Vol. 15 ›› Issue (8) : 115 -125. DOI: 10.1016/j.eng.2021.03.013

研究论文

韩珮 ^a ,
李丽莎 ^b ,
王子熹 ^b ,
锡琳 ^c ,
于航 ^a ,
丛林 ^a ,
张正威 ^a ,
符洁 ^a ,
彭冉 ^a ,
潘利斌 ^a ,
马殊荣 ^a ,
王学艳 ^d ,
王洪田 ^d ,
王向东 ^e ,
王琰 ^a ,
孙劲旅 ^b ,
蒋建东 ^a

作者信息 +

Multi-Omics Analysis Provides Insight into the Possible Molecular Mechanism of Hay Fever Based on Gut Microbiota

Pei Han ^a ,
Li-Sha Li ^b ,
Zi-Xi Wang ^b ,
Lin Xi ^c ,
Hang Yu ^a ,
Lin Cong ^a ,
Zheng-Wei Zhang ^a ,
Jie Fu ^a ,
Ran Peng ^a ,
Li-Bin Pan ^a ,
Shu-Rong Ma ^a ,
Xue-Yan Wang ^d ,
Hong-Tian Wang ^d ,
Xiang-Dong Wang ^e ,
Yan Wang ^a ,
Jin-Lyu Sun ^b ,
Jian-Dong Jiang ^a

Author information +

文章历史 +

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摘要

由于过敏性疾病在世界范围内流行且尚无治愈方法，因此有必要探讨其病理生理机制。由于过敏性疾病与肠道菌群失调相关，本研究从宿主与微生物的分子层面，结合代谢组学和微生物组学，寻找可能的机制。本研究对SD大鼠注射青蒿花粉提取物以诱导其对花粉的过敏反应，这种过敏反应降低了血液中的缬氨酸、异亮氨酸、天门冬氨酸、谷氨酸、谷氨酰胺、吲哚丙酸和肌醇浓度，并减少了粪便中的短链脂肪酸（SCFA）。来自于瘤胃球菌科（Ruminococcaceae）、毛螺菌科（Lachnospiraceae）和梭状芽孢杆菌（Clostridiales）的几个有益菌属在模型组中表达减少，而幽门螺杆菌Helicobacter 和阿克曼氏菌Akkermansia 仅在模型组中表达。此外，模型组肠道claudin-3 和肝脏脂肪酸结合蛋白表达下调，与代谢变化和细菌有关。本文的研究结果表明，氨基酸及其衍生物（尤其是缬氨酸和色氨酸的还原产物吲哚丙酸）、短链脂肪酸和肠道微生物（特别是幽门螺杆菌Helicobacter 和阿克曼氏菌Akkermansia）的改变可能通过抑制claudin蛋白表达和影响黏液层而破坏肠道屏障功能，进而导致花粉过敏。

Abstract

Due to the worldwide epidemic of allergic disease and a cure nowhere in sight, there is a crucial need to explore its pathophysiological mechanisms. As allergic disease has been associated with gut dysbiosis, we searched for a possible mechanism from the perspective of the molecular interface between host and microbiota with concurrent metabolomics and microbiome composition analysis. Sprague-Dawley rats were injected with Artemisia pollen extract to stimulate a hyper reaction to pollen. This hyper reaction decreased the circulation of valine, isoleucine, aspartate, glutamate, glutamine, indole-propionate (IPA), and myo-inositol, and reduced short-chain fatty acids (SCFAs) in feces. Several beneficial genera belonging to Ruminococcaceae, Lachnospiraceae, and Clostridiales declined in the model group, whereas Helicobacter and Akkermansia were only expressed in the model group. Furthermore, the expression of intestinal claudin-3 and liver fatty acid binding protein was downregulated in the model group and associated with metabolic changes and bacteria. Our results suggest that alterations in amino acids as well as their derivatives (especially valine, and IPA which is the reductive product of tryptophan) , SCFAs, and the gut microbiome (specifically Akkermansia and Helicobacter) may disrupt the intestinal barrier function by inhibiting the expression of claudin proteins and affecting the mucus layer, which further results in hay fever.