Could gut bacteria be a new target to restore myelin sheaths?
1. The premise. The human body is colonised by trillions of bacteria, most of which live in our intestines. In return for our hospitality, many of these microbial tenants perform useful functions: they produce vitamins, help us digest certain foods and prevent the overgrowth of harmful bacteria.
It is becoming increasingly recognised that these gut microbes play important roles in health and disease. These roles are not confined to the gut: by interacting with the immune system and producing chemical signals, our microbes can have far reaching effects throughout the body. As such, altered gut bacteria have been linked with a range of diseases including obesity, diabetes and rheumatoid arthritis.
Recently published data shows that gut microbes and the substances they produce can have a profound impact on the activity of microglia, immune cells in the brain and spinal cord. When myelin is damaged, microglia help to coordinate the growth of progenitor cells to replace the myelin sheaths. This opens up an exciting possibility: could altering gut microbes, which would in turn alter the activity of microglia, be a new means to enhance myelin sheath regeneration?
2. The project. Our project asks this question by using mice with modified gut microbes. Through a unique collaboration with the Dr Denise Fitzgerald's laboratory at Queen's University, Belfast, we are able to investigate whether mice with depleted of even no microbes restore their myelin sheaths differently to normal mice.
3. Progress to date. These experiments are complex and time-consuming to establish. However, so far, we have found that depleting gut bacteria with antibiotics appears to change the type of microglia visible at the site of myelin damage. There is a dramatic reduction of the type of microglia cells (so called "Ml" microglia) that are associated with failure of the progenitor cells to become new oligodendrocytes and produce new myelin sheath. This is a very positive finding that has encouraged us to progress to the next phase of the project.
4. What next? Over the next 18 months or so, our aim is to further characterise the changes that gut microbes can bring about in microglial cells. In particular, we will investigate whether this reduction in "Ml" microglia accompanies an increase in "M2" microglia, which are linked with efficient regeneration. By transplanting microbes from one mouse to another, we will see whether any effect can be modulated in adult animals and thus have therapeutic potential. In parallel, we will investigate whether these changes in microglia do in fact change the way the myelin sheaths regenerate, in a way that could have functional implications for humans.
5. What might this mean? A positive result would be very exciting, not least because gut microbes can be easily modified by diet, antibiotics and ingestion of purified bacteria. These may offer simple interventions by which an individual affected with MS or another myelin disease could improve their quality of life and optimise the outcome of future remyelination therapies.
RIM Franklin and CM McMurran 23/10/15