‘I feel it in my gut’ – an unexpected relationship between gut bacteria and brain disease in dogs

Summary of a recent CHF-sponsored paper published in PLOS One: ‘The Association of Specific Constituents of the Fecal Microbiota with Immune-Mediated Brain Disease in Dogs’.

 By Dr. Nick Jeffery Texas A&M University

Why did we do this study?

Meningoencephalomyelitis of unknown origin (MUO, also known by owners and veterinarians by many other names, such as GME) is a serious inflammatory disease that affects the brain and spinal cord of dogs. The cause has long been recognized to be an abnormality of the immune system, so that the body ‘attacks’ components of its own nervous system and causes inflammation. Although this is well established, it is not known why this happens.

Part of the answer is almost certainly a genetic predisposition – we know that some breeds, notably Maltese, Yorkshire Terriers, Chihuahuas and Pugs – seem to get the condition more commonly than other dogs, although it is possible for any type of dog (including cross breeds) to be affected. Even so, we know that not ALL dogs of susceptible breeds get the condition, leading to a suspicion that there must be a trigger that sets the disease in motion. Before we did this study it had been suspected that a hidden infection might be the culprit but, despite a great deal of searching, no evidence for an infectious cause has been found. 

However, around 2010, experiments in rats and mice had started to suggest that a similar disease, called experimental allergic encephalomyelitis (EAE), that is often studied because it mimics some aspects of multiple sclerosis (MS) in people, might be more easily triggered in individuals that had specific types of bacteria in their gut (gastrointestinal system). The theory that developed was that bacteria in the gut influence the immune system and specific types can make it less, or more, likely to generate an inflammatory response. 

What did we do?

When we started our study in 2012 we thought that, if a similar disease in rodents might be triggered by a specific type of bacteria in the gut, then the same might be true for dogs with MUO. So, what we did was to compare the bacteria in the gut of dogs that had MUO with those that didn’t.

To do this, we collected fecal (stool) samples from dogs that came into our clinic and were diagnosed with MUO – in the usual way – by carrying out MRI and taking a sample of the cerebrospinal fluid (CSF) for analysis. Because we know that dogs of specific breeds are susceptible to MUO we also collected samples from dogs that were of the same breed and age as the ones that were diagnosed with MUO. This meant that we could ensure that any differences we found in bacteria were not due to the breed or age of the affected dogs but might be associated with the disease itself. We were also able to ask whether other factors in the environment might have some relationship with development of MUO.

What did we find out?

The results showed that there WERE specific associations between fecal bacteria and development of MUO: the most striking finding was that there was a reduced quantity of a type of bacteria called Prevotella in the dogs with MUO. No other patterns of change in the bacteria were detected. Our result also parallels some similar work in human patients with MS and Parkinson’s disease – in which the number of Prevotella was also deficient in affected individuals.  What we don’t know is whether the reduction in the bacteria is a direct cause of the disease – or whether it might simply reflect a difference in the environment of the gut in dogs that have MUO.

What does this mean for the future?

Our conclusion from this study was that there was strong evidence that MUO might be triggered by specific imbalances in the bacteria in the gut, although this risk is layered on top of the predisposition that already exists in dogs of specific susceptible breeds. The identification of changes in gut bacteria as a specific risk is important because it suggests that it might be possible to change the risk of developing disease, or treat affected dogs, by changing the population of bacteria in the gut. This would be very attractive because it might well be relatively straightforward – and safe – to do, yet have a dramatic effect on the outcome of affected dogs. The question now is how best to change the gut bacteria – and this is what we will working on next!

This research was funded by CHF grant 1731: A Novel Approach to Understanding How Meningoencephalomyelitis Develops In Dogs

Read the full peer-reviewed research paper published in PLOS One: ‘The Association of Specific Constituents of the Fecal Microbiota with Immune-Mediated Brain Disease in Dogs’.