ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation.
ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation.
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ACE2将氨基酸营养不良与微生物生态学和肠炎联系起来。
DOI：
10.1038/nature11228
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发表时间：
2012-07-25
期刊：
影响因子：
64.8
通讯作者：
Penninger JM
中科院分区：
文献类型：
--
作者：
Hashimoto T;Perlot T;Rehman A;Trichereau J;Ishiguro H;Paolino M;Sigl V;Hanada T;Hanada R;Lipinski S;Wild B;Camargo SM;Singer D;Richter A;Kuba K;Fukamizu A;Schreiber S;Clevers H;Verrey F;Rosenstiel P;Penninger JM
血管紧张素转换酶2的突变被证明是中性氨基酸吸收不良和常驻微生物群变化的结果，使小鼠易患结肠炎;这些结果可以解释蛋白质营养不良-影响多达10亿人-如何导致肠道炎症。本文的在线版本（doi：10.1038/nature 11228）包含补充材料，可供授权用户使用。营养不良影响着发展中世界数百万人，在富裕国家仍然是一个问题，特别是对弱势群体而言。在许多情况下，正是相关的腹泻和肠道炎症导致发病和死亡。发表在这期杂志上的一项研究提出了营养不良患者对肠道炎症易感性增加的分子解释。血管紧张素转换酶2（ACE 2）在血压调节中具有核心作用，并与糖尿病、心力衰竭和病毒感染有关，已显示其影响饮食氨基酸稳态、先天免疫、肠道微生物生态和对结肠炎的易感性。缺乏这种酶的小鼠表现出色氨酸代谢受损并发展结肠炎，这可以通过饮食色氨酸及其代谢物烟酰胺来缓解。这一令人惊讶的结果解释了几个世纪以来已知的营养效应，并提供了营养不良和肠道微生物组之间的分子联系。本文的在线版本（doi：10.1038/nature 11228）包含补充材料，可供授权用户使用。营养不良影响到世界上多达10亿人，是死亡的主要原因。在许多情况下，营养不良与腹泻和肠道炎症有关，进一步导致发病和死亡。不平衡的膳食营养素影响肠道内稳态的机制在很大程度上是未知的。在这里，我们报告说，在小鼠血管紧张素I转换酶（肽基二肽酶A）2（Ace 2），它编码的一个关键的调节酶的肾素-血管紧张素系统（RAS）的缺陷，导致高度增加的易感性，由上皮损伤引起的肠道炎症。已知RAS与急性肺衰竭、心血管功能和SARS感染有关。从机制上讲，ACE 2具有RAS独立功能，调节肠道氨基酸稳态，抗菌肽的表达和肠道微生物组的生态。将来自Ace 2突变小鼠的改变的微生物群移植到无菌野生型宿主中能够传递增加的发展严重结肠炎的倾向。上皮免疫和肠道微生物群中的ACE 2依赖性变化可以通过膳食氨基酸色氨酸直接调节。我们的研究结果确定ACE 2作为饮食氨基酸稳态，先天免疫，肠道微生物生态学和结肠炎易感性的关键调节因子。这些结果为氨基酸营养不良如何引起肠道炎症和腹泻提供了分子解释。本文的在线版本（doi：10.1038/nature 11228）包含补充材料，可供授权用户使用。
Mutations in angiotensin-converting enzyme 2 are shown to predispose mice to colitis as a consequence of neutral amino acid malabsorption and a change in the resident microbiota; these results could explain how protein malnutrition — affecting up to one billion people — leads to intestinal inflammation. The online version of this article (doi:10.1038/nature11228) contains supplementary material, which is available to authorized users. Malnutrition affects many millions of people in the developing world and remains a problem in wealthy nations, especially for disadvantaged groups. In many cases, it is the associated diarrhoea and intestinal inflammation that cause morbidity and death. A study published in this issue presents a molecular explanation for the increased susceptibility to intestinal inflammation in malnutrition. Angiotensin converting enzyme 2 (ACE2), which has a central role in blood-pressure regulation and has been implicated in diabetes, heart failure and viral infection, is shown to influence dietary amino-acid homeostasis, innate immunity, gut microbial ecology and susceptibility to colitis. Mice deficient in this enzyme show impaired tryptophan metabolism and develop colitis, which is alleviated by dietary tryptophan and its metabolite, nicotinamide. This surprising result explains nutritional effects that have been known for centuries and provides a molecular link between malnutrition and the intestinal microbiome. The online version of this article (doi:10.1038/nature11228) contains supplementary material, which is available to authorized users. Malnutrition affects up to one billion people in the world and is a major cause of mortality. In many cases, malnutrition is associated with diarrhoea and intestinal inflammation, further contributing to morbidity and death. The mechanisms by which unbalanced dietary nutrients affect intestinal homeostasis are largely unknown. Here we report that deficiency in murine angiotensin I converting enzyme (peptidyl-dipeptidase A) 2 (Ace2), which encodes a key regulatory enzyme of the renin-angiotensin system (RAS), results in highly increased susceptibility to intestinal inflammation induced by epithelial damage. The RAS is known to be involved in acute lung failure, cardiovascular functions and SARS infections. Mechanistically, ACE2 has a RAS-independent function, regulating intestinal amino acid homeostasis, expression of antimicrobial peptides, and the ecology of the gut microbiome. Transplantation of the altered microbiota from Ace2 mutant mice into germ-free wild-type hosts was able to transmit the increased propensity to develop severe colitis. ACE2-dependent changes in epithelial immunity and the gut microbiota can be directly regulated by the dietary amino acid tryptophan. Our results identify ACE2 as a key regulator of dietary amino acid homeostasis, innate immunity, gut microbial ecology, and transmissible susceptibility to colitis. These results provide a molecular explanation for how amino acid malnutrition can cause intestinal inflammation and diarrhoea. The online version of this article (doi:10.1038/nature11228) contains supplementary material, which is available to authorized users.
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影响因子：
14.9
作者：
Pruesse E;Quast C;Knittel K;Fuchs BM;Ludwig W;Peplies J;Glöckner FO
通讯作者：
Glöckner FO
DOI：
10.1002/hep.23104
发表时间：
2009-09
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
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通讯作者：
Brenner DA
影响因子：
2.8
作者：
Farkas, Stefan;Hornung, Matthias;Geissler, Edward K.
通讯作者：
Geissler, Edward K.
影响因子：
64.8
作者：
Imai Y;Kuba K;Rao S;Huan Y;Guo F;Guan B;Yang P;Sarao R;Wada T;Leong-Poi H;Crackower MA;Fukamizu A;Hui CC;Hein L;Uhlig S;Slutsky AS;Jiang C;Penninger JM
通讯作者：
Penninger JM
影响因子：
82.9
作者：
Kuba K;Imai Y;Rao S;Gao H;Guo F;Guan B;Huan Y;Yang P;Zhang Y;Deng W;Bao L;Zhang B;Liu G;Wang Z;Chappell M;Liu Y;Zheng D;Leibbrandt A;Wada T;Slutsky AS;Liu D;Qin C;Jiang C;Penninger JM
通讯作者：
Penninger JM