Cell子刊:菌群代谢产物调节铁稳态
创作:szx 审核:szx 2019年12月01日
  • 乳杆菌属可感知肠道中的铁水平,并抑制宿主的铁吸收;
  • 通过高通量筛选鉴定出2种肠道菌群代谢产物——1,3-二氨基丙烷(DAP)及reuterin,可抑制缺氧诱导因子2α(HIF-2α),后者是调控肠道铁吸收的关键转录因子;
  • 另外,DAP与reuterin还可增加铁储存蛋白——铁蛋白(ferritin)的表达,导致宿主的肠道铁吸收减少;
  • 机制上,DAP与reuterin通过阻断HIF-2α的异源二聚化以抑制其活性;
  • DAP与reuterin可有效缓解小鼠模型的系统性铁过载。
主编推荐语
szx
在体内的铁有限时,肠道菌群与宿主之间如何竞争铁资源尚未明确。Cell Metabolism上发表的一项最新研究,发现肠道菌群可通过产生特定代谢产物,抑制缺氧诱导因子2α(HIF-2α)的活性,并增加铁蛋白的表达,以抑制宿主的肠道铁吸收。该研究提示,肠道菌群或可作为铁失调的治疗靶点。
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Cell Metabolism [IF:21.567]

Microbial Metabolite Signaling Is Required for Systemic Iron Homeostasis

菌群代谢产物信号对于系统性铁稳态是必需的

10.1016/j.cmet.2019.10.005

2019-11-07, Article

Abstract & Authors:展开

Abstract:收起
Iron is a central micronutrient needed by all living organisms. Competition for iron in the intestinal tract is essential for the maintenance of indigenous microbial populations and for host health. How symbiotic relationships between hosts and native microbes persist during times of iron limitation is unclear. Here, we demonstrate that indigenous bacteria possess an iron-dependent mechanism that inhibits host iron transport and storage. Using a high-throughput screen of microbial metabolites, we found that gut microbiota produce metabolites that suppress hypoxia-inducible factor 2α (HIF-2α) a master transcription factor of intestinal iron absorption and increase the iron-storage protein ferritin, resulting in decreased intestinal iron absorption by the host. We identified 1,3-diaminopropane (DAP) and reuterin as inhibitors of HIF-2α via inhibition of heterodimerization. DAP and reuterin effectively ameliorated systemic iron overload. This work provides evidence of intestine-microbiota metabolic crosstalk that is essential for systemic iron homeostasis.

First Authors:
Nupur K Das

Correspondence Authors:
Yatrik M Shah

All Authors:
Nupur K Das,Andrew J Schwartz,Gabrielle Barthel,Naohiro Inohara,Qing Liu,Amanda Sankar,David R Hill,Xiaoya Ma,Olivia Lamberg,Matthew K Schnizlein,Juan L Arqués,Jason R Spence,Gabriel Núñez,Andrew D Patterson,Duxin Sun,Vincent B Young,Yatrik M Shah

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