作者：小柯机器人 发布时间：2019/11/8 13:05:49
本期文章：《细胞—代谢》：Online/在线发表
美国密西根大学Yatrik M. Shah课题组研究发现，微生物代谢物信号是体内铁稳态必须的。这一研究成果2019年11月7日在线发表在国际学术期刊《细胞—代谢》上。
研究证明了土著细菌具有铁依赖性机制，可以抑制宿主铁的运输和储存。使用微生物代谢物的高通量筛选，课题组发现，肠道菌群产生的代谢物会抑制低氧诱导因子2α（HIF-2α）。它是肠道铁吸收的主要转录因子，并增加铁存储蛋白铁蛋白，从而导致宿主肠道对铁吸收减少。研究人员通过抑制异二聚化作用，确定了1,3-二氨基丙烷（DAP）和罗伊特林作为HIF-2α抑制剂，DAP和罗伊特林可有效缓解全身铁超负荷。这项工作提供了肠道菌群代谢串扰的证据，其对于系统性铁稳态是必不可少的。
据了解，铁是所有活生物体所需的主要微量营养元素。在肠道中竞争铁，对于维持土著微生物种群和宿主健康至关重要。在铁限制期间，宿主与天然微生物之间的共生关系如何维持尚不清楚。
附：英文原文
Title: Microbial Metabolite Signaling Is Required for Systemic Iron Homeostasis
Author: 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 Nunez, Andrew D. Patterson, Duxin Sun, Vincent B. Young, Yatrik M. Shah
Issue&Volume: November 07, 2019
Abstract: Iron is a central micronutrient needed by all living organisms. Competition for ironin the intestinal tract is essential for the maintenance of indigenous microbial populationsand for host health. How symbiotic relationships between hosts and native microbespersist during times of iron limitation is unclear. Here, we demonstrate that indigenousbacteria possess an iron-dependent mechanism that inhibits host iron transport andstorage. Using a high-throughput screen of microbial metabolites, we found that gutmicrobiota produce metabolites that suppress hypoxia-inducible factor 2α (HIF-2α)a master transcription factor of intestinal iron absorption and increase the iron-storageprotein ferritin, resulting in decreased intestinal iron absorption by the host. Weidentified 1,3-diaminopropane (DAP) and reuterin as inhibitors of HIF-2α via inhibitionof heterodimerization. DAP and reuterin effectively ameliorated systemic iron overload.This work provides evidence of intestine-microbiota metabolic crosstalk that is essentialfor systemic iron homeostasis.
DOI: 10.1016/j.cmet.2019.10.005
Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30560-1
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