Researchers from Brigham and Women’s Hospital (MA, USA) have discovered that levels of a specific miRNA increase during peak disease in a mouse model of multiple sclerosis (MS) and in untreated MS patients. The study, published in Cell Host & Microbe, indicated that when a synthetic version of the miRNA was orally administered to the mice, it prevented disease.
“We’ve discovered a new mechanism to regulate the microbiome and treat human disease that hadn’t been know before,” commented senior author Howard Weiner (Brigham and Women’s Hospital).
In order to investigate how the composition of the gut microbiome affects the course of MS, the researchers studied the microbiome and miRNAs of the experimental autoimmune encephalomyelitis model of MS. Unexpectedly, they observed that the mice that received transferred fecal matter from diseased mice were protected from disease.
The team noted that a specific miRNA, known as miR-30d, was responsible for preventing the disease. This miRNA was also reported to be enriched in untreated, relapsing–remitting MS patients.
In order to further investigate the effects of miR-30d, the researchers developed a synthetic form that they could orally administer to the mice. Upon treating the mice with the synthetic miR-30d, they demonstrated that this also protected them from disease.
They then examined what components of the microbiome were changing in response to miR-30d and discovered it was influencing a specific bacterial strain known as Akkermansia muciniphila, allowing to it to grow and flourish in the gut. This strain is known to have anti-inflammatory properties.
The researchers went on to investigate the influence of miR-30d and A. muciniphila in regulatory T cells. They reported that when the miRNA allowed the bacterial strain to proliferate in the gut, the number of regulatory T cells also increased and helped supress MS-like symptoms in the mice.
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Lead author, Shirong Liu (Brigham and Women’s Hospital), commented: “It’s unexpected and perhaps counter-intuitive that something we find in the microbiome during peak disease could provide protection, but we hypothesize that the effects we’re seeing represent a protective mechanism. Most patients with relapsing–remitting MS spontaneously recover from acute attacks. What we’ve found here may be a part of that recovery rather than a reflection of disease progression.”
There is a long way to go before these findings can be translated into therapy for patients, but the researchers are currently exploring the potential of this field and pursuing the next steps to bring these results closer to clinical impact.
“The gut microbiome is known to play an important role in MS and other diseases. Our findings, which show that a miRNA can be used to target and influence the microbiome with precision, may have applicability for MS and many other diseases, including diabetes, ALS, obesity and cancer,” commented Weiner. “A major question in the field today is how to modulate the microbiome with specificity. We find that miRNAs may hold the answer.”