neuron

Oral administration of a MicroRNA molecules harvested from the faeces of autoimmune-diseased mice, may hold potential for Multiple Sclerosis (MS) treatment in humans. The study published in Cell Host & Microbe unexpectedly found that treatment with a synthetic molecule alleviated symptoms of the disease.

Multiple Sclerosis is a degenerative autoimmune disease that targets the Central Nervous System (CNS) resulting in blurred vision, difficulty walking, and altered emotions. The immune system mistakenly targets the CNS and strips away the protective coating around the nerve fibres disrupting signals to and from the brain. Why the immune system starts attacking the body is unknown but over 200 genes have been implicated. In addition, diet, viral infection, or being female, are known factors.

Changes in Gut Microbiota

Previous studies have reported altered commensal abundances in the microbiomes of MS patients and hypothesised how this might disturb the gut-brain connections involved in the immune response. Akkermansia muciniphila, is one species which has an increased abundance in patients. Curiously this is not a negative as the bacteria are not pathogenic, but a known hallmark in MS gut microbiomes. These helpful bacteria have been shown to have many beneficial properties in regard to health with decreased amounts linked to Progeria (a rare autosomal condition that causes premature ageing) and a shorter lifespan.

The researchers used mice models with experimentally induced autoimmune encephalomyelitis (EAE) and transferred their faeces at the peak-disease stage to EAE-induced mice. This resulted in an increase of A. muciniphila and subsequently the group found enrichment of a microRNA called miR-30d they had isolated. Synthetic miR-30d given orally was found to expand A. muciniphila populations in diseased mice and alleviate symptoms.

What are microRNAs?

Micro RNA (miRNA) are stable RNA molecules of around 22 nucleotides. These molecules silence messenger RNA (mRNA) by complementary base pairing, forming double stranded RNA which marks the whole lot for degradation. miRNAs have important biological functions in silencing and due to their surprising resilience are found in the gut and faeces of humans. By surviving the digestive process, the miRNA can influence the host’s gut bacterial community, entering bacterium via horizontal gene transfer.

This study demonstrated that miR-30d could survive the entire digestive process and enter A. muciniphila. This is thought to be a protective response mechanism triggered by MS, as most patients recover from acute attacks without treatment. What is most exciting was the treatment of miR-30d providing a protection against MS, suggesting that the guts of patients might be enriched with therapeutic properties.

Purposeful changes in the gut microbiome are being explored as a therapy for many diseases such as colorectal cancer. Currently there are over 200 registered clinical trials for faecal microbiome transplantation. This may not sound appealing but as gut bacteria have been shown to impact diet, metabolism, and disease, it might be time to embrace what’s in our, or other’s guts.

More on these topics