Clinical corner
Oct 21, 2022

Gut-brain-axis: where is research headed

Gut-brain-axis: where is research headed
Join us for a casual chat with world-renowned Professor Ted Dinan MD as he discusses research trends, clinical findings, and more.

Emeritus Professor of Psychiatry and a Principal Investigator in APC Microbiome Ireland at University College Cork. He has been mentioned as part of the Highly Cited Researchers, by Clarivate Analytics. and by Expertscape.  Prof. Dinan has promoted the concept of Psychobiotics, probiotics that have a mental health benefit.His main research interest is on the role of the gut microbiota in influencing brain function and development. He has focused on depression and irritable bowel syndrome and has made significant contributions to the literature on the regulation of the hypothalamic-pituitary-adrenal axis in situations of stress. In 1995 was awarded the Melvin Ramsey Prize for this research into the biology of stress. He has published over 400 papers and numerous books on the pharmacology and neurobiology of affective disorders.

Why should we be interested in the gut microbiota?

It's really only within the last 15 to 20 years that research into the gut microbiota has taken place. Prior to that, we regarded gut microbes as simply commensal bacteria that we fed but really had no function within our bodies. We now know that these microbes play a very fundamental role in regulating the activity of organs throughout the body.

What determines our Microbiota?

Well, there were many factors determining the architecture or the structure of our gut microbiota. In adults, the most important determinant is our diet. If one is on a healthy diet, that's a diet of fruits and vegetables and fish and just a generally healthy tends to have a complex and relatively diverse microbiota. On the other hand, it is clear from ongoing studies that if somebody is on a diet of fast food or highly processed food, that the architecture of the microbiota alters and we lose the diversity that one sees on a gut microbiota. Now, other factors that will determine the microbiota that any of us possess at any point in time will be things like exercise. We know from activity or publications over the past five to ten years that people who engage in aerobic exercise on a regular basis tend to have quite a diverse microbiota. We also know that certain things can have a negative effect on the microbiota apart from diet. For instance, if somebody is under enormous stress that can impact the gut microbiota and of course, there are a variety of medications that also would impact one way or the other around the microbiota. So there's a range of things that can influence our microbiota, but undoubtedly our diet is the dominant factor.

What specific areas of Microbiome research are you most excited about?

Well, I suppose as a psychiatrist, my interest is in how stress can influence our mental health and when one looks at the impact of stress on mental health. Undoubtedly, depression and anxiety disorders are the more common conditions in our society driven by stress, and I'm very much excited by the possibility of targeting the gut microbiota to alleviate symptoms of depression or anxiety. Because right up until now, the most common way is certainly the way in which I would treat depression at my clinic is to use antidepressants, and of course, to use psychological therapies like cognitive behavioral therapy as well. But I think we're getting to a point now where we will be able to improve the mental functioning of people with depression or anxiety by targeting the gut microbiome.

How do you see microbiome research and products developing to show benefits in counteracting lifestyle diseases, such as Alzheimer or Depression?

Right now, I think as we move forward, the gut microbiota can be targeted in a number of ways. It can be targeted to reduce risk factors of the disease and it can be targeted to actually treat the disease itself. For many complex disorders like, let's say, dementing illnesses, which are ever-increasing in our western societies. I think that in the short to medium term, we can target the gut microbiota to reduce the risk factors of dementia, for instance, you know, to reduce cholesterol levels, to reduce glucose levels and other factors that we know contribute to the risk of dementing illnesses. I don't believe that right now we're anywhere near being able to treat disorders like Alzheimer's disease or Parkinson's disease with microbial interventions. And I wonder if we ever will if we take as a disorder like Parkinson's disease. We know and we've known for a long time that is due to degeneration of dopamine neurons within the brain. Now maybe the disease originates in the gut, but I think if the dopamine neurons in the brain are lost, it is unlikely that any gut intervention is going to treat Parkinson's disease. No, that does not mean that we couldn't reduce risk factors for Parkinson's disease and prevent the emergence of Parkinson's disease, which is a very common disease in our society. But I'm not convinced that we will be able to reverse the symptoms of a disease like Parkinson's disease or Alzheimer's disease by targeting the gut microbiota.

Having published over 400 papers and been a part of so many research projects in Microbiome research, what would you say is the most important piece to designing a Microbiome research trial?

Right. Well, I would have to say at the outside outset that really, whilst we have a lot of very good preclinical studies in microbiome science, we are still lacking good quality research in relation to clinical aspects of the microbiota. Now, I pride myself on designing trials that are adequate to demonstrate an effect and that don't cost enormous sums of money. Anyone can devise a study that is going to cost a fortune. But I do think that one of the big problems in this area is that you have poor research design and the studies are underpowered. The number of subjects recruited is inadequate given the sorts of design that are used. So really, it depends on the phase of the study. If it's a very early stage study, you probably don't want to do a random allocation parallel group design. But if it's later on, you clearly do. So I think what we need really to move this entire field forward is really properly powered studies that really demonstrate the efficacy of products.

Do drugs impact the microbiota?

It's estimated that about 75 to 80% of all of the drugs that are widely prescribed in the US and Europe impact the gut microbiota. And many of them impact the gut microbiota in negative ways. Antidepressants, which paradoxically can be impacting in relation to the the mood state of the individual, can have a negative impact on the gut microbiota. Drugs like proton-pump inhibitors and I find that my clinic half the population seem to be on proton-pump inhibitors undoubtedly impact negatively the gut microbiota. There are other medications like, for example, lithium has been around since the 1960s as a means of stabilizing mood in patients with bipolar illness or manic depression. And we've shown that lithium can actually increase the diversity of the gut microbiota. In other words, it seems to have a positive benefit from the microbiota perspective. But really, I think the important message for any clinician is that at least 75% of all of the drugs we prescribe do impact the gut microbiota in one way or another.

As we see more and more research about the gut-brain axis, and as a specialist in this field, what new therapies do you see on the horizon?

Right, well, as a psychiatrist, what I hope to see within the next few years is the emergence of psychobiotics or probiotics that are effective in treating milder forms of depression and anxiety. I think that is a really achievable goal within the next two years. And I think would have a major societal impact. Depression is the most common disorder in our society. It has the highest level of morbidity, according to the World Health Organization. And if we could develop, and I believe we can probiotics or psychobiotics as I prefer to call them, that would treat milder forms of depression, I think that would have a major benefit. And of course, you know, we have antidepressants. I mean, very effective antidepressants for many people, but for a variety of reasons, many individuals who suffer from milder forms of depression whilst there might be incapacitated as a result of the milder form of depression, do not wish to take antidepressants. So I think a natural alternative to antidepressants would be very valued by the consumer.

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