The Host Shapes the Gut Microbiota via Fecal MicroRNA.

The Host Shapes the Gut Microbiota via Fecal MicroRNA.
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宿主通过粪便microRNA控制肠道微生物群。

DOI:
10.1016/j.chom.2015.12.005
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发表时间:
2016-01-13
影响因子:
30.3
通讯作者:
Weiner HL
Weiner HL
中科院分区:
医学1区
文献类型:
--
作者:
Liu S;da Cunha AP;Rezende RM;Cialic R;Wei Z;Bry L;Comstock LE;Gandhi R;Weiner HL

文献摘要

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宿主肠道微生物区系因物种和个体而异,但在个体内随着时间的推移相对稳定。宿主如何选择性地塑造微生物区系在很大程度上还不清楚。在这里,我们证明了粪便微RNA(MiRNA)介导的物种间基因调控有助于宿主对肠道微生物区系的控制。MiRNAs在小鼠和人类粪便样本中含量丰富,并存在于细胞外小泡中。细胞特异性的miRNA加工酶的丢失,Disher,确定肠上皮细胞(IEC)和Hopx阳性细胞是主要的粪便miRNA来源。这些miRNAs可以进入细菌,如核假单胞菌和大肠杆菌,专门调节细菌的基因转录,影响细菌的生长。IEC-miRNA缺陷(Dicer1ΔIEC)小鼠表现出肠道微生物区系失控并加重结肠炎,而WT粪便miRNA移植可恢复粪便微生物并改善结肠炎。这些发现既确定了粪便miRNA塑造肠道微生物区系的生理作用,也确定了操纵微生物群的潜在策略。
The host gut microbiota varies across species and individuals but is relatively stable over time within an individual. How the host selectively shapes the microbiota is largely unclear. Here, we show that fecal microRNA (miRNA)-mediated inter-species gene regulation facilitates host control of the gut microbiota. MiRNAs are abundant in mouse and human fecal samples and present within extracellular vesicles. Cell-specific loss of the miRNA-processing enzyme, Dicer, identified intestinal epithelial cells (IEC) and Hopx-positive cells as predominant fecal miRNA sources. These miRNAs can enter bacteria, such as F. nucleatum and E. coli, specifically regulate bacterial gene transcripts and affect bacterial growth. IEC-miRNA deficient (Dicer1ΔIEC) mice exhibit uncontrolled gut microbiota and exacerbated colitis and WT fecal miRNA transplantation restores fecal microbes and ameliorates colitis. These findings identify both a physiologic role by which fecal miRNA shapes the gut microbiota and a potential strategy for manipulating the microbiome.