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

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...

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Bibliographic Details
Published in:Cell host & microbe Vol. 26; no. 6; p. 779
Main Authors: Liu, Shirong, Rezende, Rafael M, Moreira, Thais G, Tankou, Stephanie K, Cox, Laura M, Wu, Meng, Song, Anya, Dhang, Fyonn H, Wei, Zhiyun, Costamagna, Gianluca, Weiner, Howard L
Format: Journal Article
Language:English
Published: United States 11.12.2019
Subjects:
Administration, Oral
Animals
Encephalomyelitis, Autoimmune, Experimental - drug therapy
Encephalomyelitis, Autoimmune, Experimental - immunology
Fecal Microbiota Transplantation
Feces
Gastrointestinal Microbiome - immunology
Host Microbial Interactions
Humans
Lactase - metabolism
Mice
Mice, Inbred C57BL
MicroRNAs - metabolism
MicroRNAs - therapeutic use
Multiple Sclerosis - drug therapy
T-Lymphocytes, Regulatory - metabolism
Verrucomicrobia - growth & development
Verrucomicrobia - immunology
Verrucomicrobia - metabolism
autoimmune diseases
fecal transplantation
microvesicle
experimental autoimmune encephalomyelitis
multiple sclerosis
microRNA
Akkermansia muciniphila
regulatory T cell
microbiome
host-microbe interaction
ISSN:1934-6069, 1934-6069
Online Access:Get more information
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Summary: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.
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ISSN:1934-6069
1934-6069
DOI:10.1016/j.chom.2019.10.008