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

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Oral Administration of miR-30d from Feces of MS Patients Suppresses MS-like Symptoms in Mice by Expanding Akkermansia muciniphila.
Cell Host & Microbe ( IF 20.6 ) Pub Date : 2019-11-26 , DOI: 10.1016/j.chom.2019.10.008
Shirong Liu ₁ , Rafael M Rezende ₁ , Thais G Moreira ₁ , Stephanie K Tankou ₁ , Laura M Cox ₁ , Meng Wu ₂ , Anya Song ₁ , Fyonn H Dhang ₁ , Zhiyun Wei ₃ , Gianluca Costamagna ₁ , Howard L Weiner ₁

Affiliation

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.

中文翻译：

口服多发性硬化症患者粪便中的 miR-30d 通过扩大阿克曼氏菌（Akkermansia muciniphila）来抑制小鼠的多发性硬化症样症状。

健康捐赠者的粪便转移正在被探索作为一种微生物组模式。人们发现 MicroRNA (miRNA) 会影响微生物组。多发性硬化症（MS）患者已被证明肠道微生物组发生了改变。在这里，我们出乎意料地发现，从多发性硬化症的实验性自身免疫性脑脊髓炎 (EAE) 模型中收集的粪便在疾病高峰期以 miRNA 依赖性方式改善受体的疾病。具体来说，我们发现 miR-30d 在 EAE 高峰期和未经治疗的 MS 患者的粪便中富集。口服合成 miR-30d 可通过扩增调节性 T 细胞 (Treg) 改善 EAE。从机制上讲，miR-30d 调节 Akkermansia muciniphila 中乳糖酶的表达，从而增加肠道中 Akkermansia 的丰度。扩大的阿克曼氏菌反过来会增加 Tregs 来抑制 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。

更新日期：2019-11-27

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