Dataset Information

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

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.

SUBMITTER: Liu S

PROVIDER: S-EPMC6948921 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Publications

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

Liu Shirong S Rezende Rafael M RM Moreira Thais G TG Tankou Stephanie K SK Cox Laura M LM Wu Meng M Song Anya A Dhang Fyonn H FH Wei Zhiyun Z Costamagna Gianluca G Weiner Howard L HL

Cell host & microbe 20191126 6

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 ...[more]

PMID: 31784260

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Project description:Akkermansia muciniphila is considered a next-generation probiotic because of its immense potential to regulate disorders. We isolated 31 strains of A. muciniphila from feces or breast milk of healthy people. After genome sequencing, assembly, and analysis, we selected six strains (AM01 to AM06) for further exploration. We first analyzed their general characteristics, including morphological description, growth characteristics, and physiological and biochemical characteristics, and then confirmed their genetic characteristics, including GC content, putative virulence factors, and antibiotic resistance genes. We next investigated the tolerance of these strains to artificial gastric and intestinal fluids and bile salts to evaluate their survival potential in the digestive tract. Drug sensitivity tests were also conducted based on the analysis of the antibiotic resistance genes of these strains. Furthermore, we examined the genetic stability and acute toxicity of two strains (AM02 and AM06) in mice. Finally, the safety of AM06 was evaluated in normal mice and nude mice. AM06 exhibited adaptability to pH changes. Since AM02 and AM03 showed more resistance to antibiotics than AM01 and AM04 to AM06, their potential clinical application may be limited. Both AM02 and AM06 were genetically and phenotypically stable and safe in normal mice, and AM06 was safe in nude mice. Considering all this together, AM06 is a safe A. muciniphila strain and exhibits a great potential for use as a probiotic strain among the isolated strains. IMPORTANCE In this study, we isolated 30 strains of Akkermansia muciniphila from different samples of human feces, and for the first time we isolated an A. muciniphila strain from human breast milk. This isolation verified the existence of microbes in human breast milk, which suggests that A. muciniphila can be vertically propagated from mother to infant and participates in the formation of the early gut microbiome. We then systematically evaluated the potential for use as a probiotic of this A. muciniphila strains according to the FAO/WHO recommendation. We confirmed that the AM06 strain isolated from breast milk has no virulence factors and is genetically stable and nonpathogenic for both normal mice and nude mice. Moreover, its tolerance to pH changes and bile salts indicates its desirable probiotic properties. Thus, we propose that the AM06 strain of A. muciniphila is safe for use as a probiotic candidate.

Dataset Information

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

Publications

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

Similar Datasets

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