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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Vydáno v:	Cell host & microbe Ročník 26; číslo 6; s. 779
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 11.12.2019
Témata:	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
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1934-6069 1934-6069
DOI:	10.1016/j.chom.2019.10.008