Microbes and neurological health

Could there be a link between the health of your gut microbiome and your neurological health? Phil Sansom spoke to Simon Carding from University of East Anglia and the Quadrum Institute...

Simon - It's quite clear from studies looking at dementia patients, in particular Parkinson's Disease, that G.I. symptoms, that's gut disorders, seem to precede the onset of the classical Parkinson's symptoms. Several research groups have shown using animal models of Parkinson's disease, that microbes might be playing a causative role in Parkinson's disease, and again, it’s through the production of things that interfere with the communication, or they actually make the misfolded proteins that cause some of the defects in the brains of dementia patients, they can actually make them themselves, to exacerbate the disease process.

Phil -  Now this system, this gut-microbe-to-brain axis, how do you actually investigate and do science on it?

Simon - There are two principal ways; one is in laboratories, in culture dishes, where we can isolate cells of particular interest. So for example, cells that make up the blood-brain-barrier, or cells that line the gut. Using these culture based systems we can look at what impact particular gut microbes, or their products, have on these cells. Does it change their pattern of behaviour, does it change the factors they produce, the hormones, or the neurotransmitters. And then for more directly relevant studies we’d move into animal models. So the mouse is used as a classical model for this. But what we really need is more human based studies to look at particularly the role the gut microbes might play in cognitive failure and dementia development.

Phil - What are your main question, or questions specifically?

Simon - Well we'd really like to know; are the changes in gut microbe populations seen in dementia patients a cause of the disease process, or are they a consequence or an effect of the disease. So to do this we have to do longitudinal studies, that's looking at people over a significant period of time, trying to identify what occurs first, and what sequence of events occurs in these patients that ultimately leads to declining cognitive function, and develop dementia.

So we have one such study underway at the moment. It’s called The Motion Study, in which we're looking at individuals 60 years of age and older. We assess their cognitive function and according to the performance of those tests we categorise individuals as low, medium, or high risk for developing dementia. And we'll follow those over a period, initially for four years, but hopefully longer, where we'll perform tests on looking at their gut microbe populations that were present in the stool samples, looking for changes in there, do they occur prior to significant change their cognitive function. But we're also looking at the structure of the brain, so we do MRI scans.

And interestingly, we're also looking at the eye, because the eyes not only the window to the brain but it's one of the fastest aging organs in the body. So again we're looking for: What are the first indicative changes in the eye, the brain, the gut, that give a signature for this patient is starting to develop dementia. And of course if we can identify these key tipping points if you like, then we can identify means of which we can hopefully intervene.

Phil - And when you're looking at the microbiome of these people, do people developing or who have Parkinson's have noticeably different microbiomes, or does everyone just have a very different pattern?

Simon - Everybody's microbiome is unique, it's like your microbial fingerprint if you like, but everybody has a core population of microbes which are important, particularly for food digestion. But what's been shown in Parkinson's patients, and Alzheimer's patients as well, is they have distinctive changes in their gut microbe populations.

Phil - So when you replicate those in your petri dishes and in your mice, what changes do you notice?

Simon - Of course, it's very difficult to recapitulate in a Petri dish or tissue culture plate the complexity of the gut and the complexity of the microbial constituents. We're looking at only a representation of what's present, but some of the changes we're seeing are these changes in the gut microbe populations that is associated with an increased leakiness of the gut, called leaky gut syndrome, and a leaky gut would allow microbes and their products more easily, or more readily accessible to the bloodstream. And again this could exacerbate certain diseases, and the classical example for this is inflammatory bowel disease. So there may be a common link to some other quite serious diseases. But in this case it would have an impact on the brain for dementia patients.

Phil - Does it cause dementia?

Simon - Well certainly the animal studies are pointing a strong finger of suspicion at gut microbes being part of the cause of dementia. So these transplant studies that had been done in mice had quite striking effects, and make the disease clearly much worse than if normal microbes from a healthy individual are transferred into those mice.

So there is if you like, a smoking gun for gut microbes right now, and you know, the evidence is quite compelling, but we really need to substantiate that and to validate the studies, by looking more closely in humans, and particularly individuals prior to the onset of clinical symptoms. If they are really a major cause of disease then there's means by which we can manipulate gut microbes to alleviate or maybe even stop the symptoms developing. I mean the classic one would be probiotics for example, or prebiotics, or even faecal microbiota transplantation, the wholesale replacement of somebody's gut microbe population with one that's a more healthy one for example. So there are quite a few interesting possible interventions if we do in fact find gut microbes are a cause of this disease.

Phil - And lastly, in this show we are talking about quote unquote gut feelings.

Simon - Yes yes.

Phil - What do you think about how gut microbes can change the way that you feel?

Simon - Yes it's very interesting. So I mean emotions play a critical role in the ability to make fast and rational decisions. These emotions are generated on physiological changes to stimuli, and this could be manifest as muscle tone, heart rate, hormone activity, and the brain transforms these emotions in an individual so it can recall if that stimulus comes again, a very rapid response which would be the emotional response.

Some of these emotions could well originate from the gut, and a physician called Emeran Mayer proposed in 2016, I believe, that from birth, gut microbe activity in response to certain stimuli produces physiological changes that are relayed to the brain. So this stimuli could be food or drugs and this could result in changes that relate to pleasure and consumption, or pain and avoidance. So in that context you can imagine that in response to certain stresses, the gut instincts, that gut feeling takes over as an immediate fast response without the brain really getting too involved in it, and that's because it's learned from previous experience.