Gut Microbiome Alters Myelination

Research Summary: Regulation of prefrontal cortex myelination by the microbiota

The Background

In recent times, there has been an increasing focus placed on the role that the gut microbiome (composed of bacteria and other single-celled organisms) can play in multiple sclerosis (MS).  Indeed, various studies over the past few years have implicated the gut microbiome in a number of different ways.  One such example showed that glatiramer acetate (Copaxone) significantly altered the bacterial population present in people on this therapy, compared to individuals not taking it.  It was hypothesised that this change may be related to Copaxone’s mode of action.  Similarly, germ-free mice (which are microbiota deficient) have provided interesting information about the role that these bacteria and other organisms may play.  

However, with this progress, it is still largely unclear as to the role that the microbiome may play in MS.

The Study

In this study, conducted by researchers at University College Cork, the effect of the microbiome on the prefrontal cortex (PFC) of the brain was analysed.  Three sets of mice were used for the experiments:  germ free mice, germ free mice that were then exposed to environmental microbes, and normal mice.  Brain tissue samples were analysed from all mice and the levels of gene and protein expression were compared.  Structural analysis was also performed using brain tissue samples.

The Findings

The analysis from this study showed a number of key factors, including that:

• Expression of genes related to myelination were significantly increased in germ free mice

• The increased genes were all involved in networks related to neuronal plasticity and myelin regulation

• Interestingly, these genes were not altered in germ free mice that had been exposed to environmental microbes.  This suggests that the impact of microbes on the expression of these genes is a very dynamic process.

• These expression level changes were only found in the prefrontal cortex and not other parts of the brain, as well as being restricted to male mice.  This indicates a region and gender specific effect of the gut bacteria on myelination.

• This change in gene expression was also found to have a physiological effect, as germ free male mice had thicker myelin sheaths surrounding axons in the prefrontal cortex.

The Outcomes

This is the first study that has identified regulation of myelination by the gut microbiome.  How this happens is still unknown and so further projects will have to be undertaken to better understand this process.  This is of particular interest in multiple sclerosis, as it may open up the potential for dietary and probiotic approaches to treatment.  Similarly, this provides further evidence as to how faecal transplantation may also provide benefits to people with MS.

The abstract of this study can be found here.