Bile Acids May Play Role in Multiple Sclerosis

Research Summary: Bile acid metabolism is altered in multiple sclerosis and supplementation ameliorates neuroinflammation

A joint investigation undertaken by researchers at Johns Hopkins University, the Cleveland Clinic and the University of California San Francisco, published in the Journal of Clinical Investigation (JCI).

What are bile acids?

As the name suggests, bile acids are found within bile.  They are formed through the metabolism or breaking down of cholesterol.  They play a role in the digestion and reabsorption of fats in the body, as well as being able to have a ‘hormone-like’ effect on cells throughout the body.  They are of interest in multiple sclerosis, as bile acids are known to impact on cells in both the central nervous system (CNS) and the immune system – both of which are critical in multiple sclerosis.  The exact role that bile acids play in multiple sclerosis is unknown, however, this recently published study has found some very interesting things, such as…

Bile acids are altered in adult and paediatric multiple sclerosis

The researchers used sensitive techniques to study the levels of these bile acids in people living with relapsing-remitting multiple sclerosis and progressive multiple sclerosis.  Initially, this was performed by analysing blood plasma in a small cohort (around 50 people per group) and then a more focussed investigation was performed on blood plasma from a larger group (~175 people living with MS).  

They found that, when compared with healthy controls, the levels of bile acids was lower in both groups of people living with multiple sclerosis.  They found that this difference was more significant in people living with progressive MS.  Interestingly, they also found a specific group of bile acids (known as secondary bile acids), were also decreased in people living with MS.  Secondary bile acids are produced through interactions with the gut microbiome, which has also been suggested to play a role in multiple sclerosis, and so the connection is worth noting.

As well as this, they found that similar differences existed in children living with multiple sclerosis, also known as paediatric MS.  This finding may suggest that whatever is occurring is not just the result of an ongoing disease, which is always difficult to determine in a chronic inflammatory disease.

Conclusion:  Bile acid levels are decreased in adults living with relapsing-remitting multiple sclerosis and progressive multiple sclerosis, as well as children living with multiple sclerosis.

There is an association between bile acids and lesions in multiple sclerosis

Having different levels doesn’t necessarily mean anything unless it can be tied to the disease process.  Earlier, it was mentioned that bile acids are able to have a ‘hormone-like’ effect on cells in the body.  They do this by binding to molecules on the surface of cells called ‘receptors’.  The researchers were interested to see whether the receptors for bile acids were present within lesions found in MS brain tissue.  Indeed, they found that there were more of these receptors present in active lesions compared to either brain tissue from healthy individuals or healthy brain tissue from people living with multiple sclerosis.  

Conclusion:  These bile acids may play a role in the inflammatory process occurring at these lesions.

Bile acid supplementation has positive effects

Since bile acid levels are low in people living with multiple sclerosis, and they appear to be at least somewhat related to the disease process, the researchers asked what would the effect be on the disease if bile acids were added.  For these experiments, they used a specific bile acid (called TUDCA – don’t worry about the full name) and checked it through two separate experiments.  They found the following:

1. TUDCA had a positive effect on cells tested in culture within the laboratory.  In particular, it stopped certain cells from being neurotoxic (i.e. toxic to the nervous system) and other cells from becoming inflammatory.  Both of these impacts would be useful in the treatment of multiple sclerosis.

2.  They also tested TUDCA in a mouse model of multiple sclerosis called EAE.  They found that treating the mice with TUDCA after they developed disease lead to clinical improvements, including behavioural improvements and reduced damage to the myelin sheath.

Conclusion:  TUDCA has beneficial effects on cells, both in laboratory experiments and animal models, that could be useful for the treatment of multiple sclerosis.  TUDCA is currently being tested in a number of human clinical trials, including one for MS.

Those wishing to read this paper in more detail can do so here.