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口服 MS 患者粪便来源的 miR-30d 通过扩张阿克曼氏菌缓解小鼠的 MS 样症状。

Oral Administration of miR-30d from Feces of MS Patients Suppresses MS-like Symptoms in Mice by Expanding Akkermansia muciniphila.

机构信息

Ann Romney Center for Neurologic Diseases, Department of Neurology, Partners Multiple Sclerosis Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.

Ann Romney Center for Neurologic Diseases, Department of Neurology, Partners Multiple Sclerosis Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.

出版信息

Cell Host Microbe. 2019 Dec 11;26(6):779-794.e8. doi: 10.1016/j.chom.2019.10.008. Epub 2019 Nov 26.

Abstract

Fecal transfer from healthy donors is being explored as a microbiome modality. MicroRNAs (miRNAs) have been found to affect the microbiome. Multiple sclerosis (MS) patients have been shown to have an altered gut microbiome. Here, we unexpectedly found that transfer of feces harvested at peak disease from the experimental autoimmune encephalomyelitis (EAE) model of MS ameliorates disease in recipients in a miRNA-dependent manner. Specifically, we show that miR-30d is enriched in the feces of peak EAE and untreated MS patients. Synthetic miR-30d given orally ameliorates EAE through expansion of regulatory T cells (Tregs). Mechanistically, miR-30d regulates the expression of a lactase in Akkermansia muciniphila, which increases Akkermansia abundance in the gut. The expanded Akkermansia in turn increases Tregs to suppress EAE symptoms. Our findings report the mechanistic underpinnings of a miRNA-microbiome axis and suggest that the feces of diseased subjects might be enriched with miRNAs with therapeutic properties.

摘要

粪便移植正被探索作为一种微生物组治疗方法。研究发现微小 RNA(miRNA)能够影响微生物组。多发性硬化症(MS)患者的肠道微生物组已经被证明发生了改变。在这里,我们出乎意料地发现,从 MS 的实验性自身免疫性脑脊髓炎(EAE)模型中采集的疾病高峰期的粪便移植,以 miRNA 依赖的方式改善了接受者的疾病。具体来说,我们表明 miR-30d 在疾病高峰期 EAE 和未经治疗的 MS 患者的粪便中富集。口服给予合成的 miR-30d 通过调节性 T 细胞(Treg)的扩增来改善 EAE。从机制上讲,miR-30d 调节黏蛋白阿克曼氏菌中乳糖酶的表达,从而增加肠道中黏蛋白阿克曼氏菌的丰度。反过来,扩增的阿克曼氏菌增加 Treg 以抑制 EAE 症状。我们的研究结果报告了 miRNA-微生物组轴的机制基础,并表明患病受试者的粪便可能富含具有治疗特性的 miRNA。

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