Genetic modification of iron metabolism in mice affects the gut microbiota

Genetic modification of iron metabolism in mice affects the gut microbiota
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DOI:
10.1007/s10534-012-9555-5
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发表时间:
2012-10-01
期刊:
影响因子:
3.5
通讯作者:
Meyron-Holtz, Esther G.
Meyron-Holtz, Esther G.
中科院分区:
生物学3区
文献类型:
--
作者:
Buhnik-Rosenblau, Keren;Moshe-Belizowski, Shirly;Meyron-Holtz, Esther G.

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肠道微生物群的组成受环境因素以及宿主遗传学的影响。铁是细菌生长所必需的重要元素之一,因此我们假设宿主铁稳态的变化可能会影响肠道的管腔铁含量,从而影响肠道细菌的组成。铁调节蛋白2(Irp 2)和遗传性血色病Hfe中突变的基因之一都是参与调节全身铁稳态的蛋白质。为了检验我们的假设,分析了来自Hfe-/-、Irp 2-/-及其野生型对照小鼠的粪便金属含量和粪便微生物群的选定谱。与野生型和Hfe-/-小鼠相比,观察到Irp 2-/-小鼠粪便中铁和其他矿物质水平升高。有趣的是,在Irp 2-/-和Hfe-/-小鼠之间观察到一般粪便细菌群体模式的显著变化。此外,五种细菌的相对丰度,主要是乳酸菌,是显着不同的小鼠品系。乳酸杆菌(L.)murinus和L. Irp 2-/-小鼠中的大肠杆菌高度丰富,屎肠球菌物种簇和与Olsenella最相似的物种在Hfe-/-小鼠和L.约翰逊氏菌在野生型小鼠中高度丰富。这些结果表明,小鼠宿主铁代谢基因的缺失影响其肠道细菌的组成。进一步研究肠道微生物群与影响人体全身铁代谢的基因突变之间的关系将产生临床意义。
The composition of the gut microbiota is affected by environmental factors as well as host genetics. Iron is one of the important elements essential for bacterial growth, thus we hypothesized that changes in host iron homeostasis, may affect the luminal iron content of the gut and thereby the composition of intestinal bacteria. The iron regulatory protein 2 (Irp2) and one of the genes mutated in hereditary hemochromatosis Hfe , are both proteins involved in the regulation of systemic iron homeostasis. To test our hypothesis, fecal metal content and a selected spectrum of the fecal microbiota were analyzed from Hfe-/-, Irp2-/- and their wild type control mice. Elevated levels of iron as well as other minerals in feces of Irp2-/- mice compared to wild type and Hfe-/- mice were observed. Interestingly significant variation in the general fecal-bacterial population-patterns was observed between Irp2-/- and Hfe-/- mice. Furthermore the relative abundance of five species, mainly lactic acid bacteria, was significantly different among the mouse lines. Lactobacillus (L.) murinus and L. intestinalis were highly abundant in Irp2-/- mice, Enterococcus faecium species cluster and a species most similar to Olsenella were highly abundant in Hfe-/- mice and L. johnsonii was highly abundant in the wild type mice. These results suggest that deletion of iron metabolism genes in the mouse host affects the composition of its intestinal bacteria. Further studying the relationship between gut microbiota and genetic mutations affecting systemic iron metabolism in human should lead to clinical implications.