The Power of Gut Bacteria to Influence Mental Health
I am a final year PhD student at the Centre for Affective Disorders at King’s College London. I would like to share with you some of our latest work on my topic of interest — the involvement of the gut in mental health. Have you ever had butterflies in your stomach? Or maybe a gut feeling? How about describing a big disappointment as being ‘gutted’? Expressions like these appear in many languages throughout the world. They are evidence that on an instinctive level we associate the gut with a range of emotions from sadness and disappointment to excitement, intuition, and even love. And even though Hippocrates postulated a role for the gut in mental illness as early as 4th century BC, modern science dismissed the gut-brain-mood relationship until fairly recently.
The bacteria in and on our bodies vastly outnumber the cells and the largest proportion of these reside in the gastrointestinal tract (the pathway in which food enters and leaves our bodies). There, they form a complex, dynamic and ever-changing ecosystem, also known as the gut microbiota. The gut microbiota performs various crucial functions for our wellbeing and survival, such as digestion, production of metabolites (that is, any substance produced during digestion), development and regulation of the immune system, and production of neurochemicals involved in mood regulation, such as serotonin. An imbalance in the microbiota (that is an increase of harmful bacteria at the expense of beneficial bacteria or a lack of bacterial diversity) has been linked to numerous medical conditions, among which are inflammatory bowel disease (IBD), obesity and some autoimmune diseases.
The Gut and Mental Illness
Most recently, owing to advances in sequencing technologies, we have been able to discover the complex bidirectional ways through which the gut microbiota communicates with the brain (also known as the gut-brain axis) and have begun to unpick its involvement in the development and progression of mental illness. For example, we have seen that microbial imbalance in the gut can increase the production of inflammatory molecules, lead to an overactivation of the hypothalamus-pituitary-adrenal (HPA) axis, which produces the stress hormone cortisol, and reductions in brain-derived neurotrophic factor (BDNF) — a protein necessary for normal neuron development and function. Interestingly, by using animal models of mental illness, researchers have shown that mice that have been transplanted microbiota (via a fecal microbiota transplant, or FMT) from a person with a condition such as depression, anxiety, autism spectrum disorder or schizophrenia developed behavioural and physiological symptoms of the respective condition, whereas mice receiving FMT from healthy people did not.
So what is different in the gut microbiota of people with mental health conditions?
Many studies have now shown that, when compared to healthy controls, people with mental health conditions have notable differences in the composition of their gut microbiota, and specifically, in the levels of specific bacteria. This has led people to believe that we could potentially treat or even diagnose mental health conditions by analysing the levels of such bacteria (via stool sample analysis) when a patient comes to the clinic. However, for us to be able to use these microbial differences to assist diagnosis, we need to first demonstrate that they are unique to the condition we want to diagnose (i.e. that they aren’t the same in someone with bipolar disorder and someone with psychosis, for example). Therefore, we first need to meticulously compare these bacterial differences across the range of psychiatric conditions.
That’s what we set out to do in our most recent paper. We reviewed and analysed the results of 59 studies of adults with a range of psychiatric conditions. You can see the full paper here, or listen to the podcast version here. What we found was that the most consistent microbial changes in the guts of people with depression, bipolar disorder, psychosis/schizophrenia and anxiety overlapped. For example, the levels of the bacteria Faecalibacterium and Coprococcus were decreased and the levels of Eggerthella were increased in these patient groups compared to controls. Faecalibacterium and Coprococcus are involved in the production of butyrate — an essential short-chain fatty acid (SCFA) that maintains a healthy gut lining and prevents inflammation. On the other hand, Eggerthella, which was enriched in patients, is involved in butyrate depletion and has also been linked to gastrointestinal inflammation. While it is likely that the changes in the microbiota are a lot more complex than that, these are examples of some notable shared features in people with several mental health conditions. Interestingly, these conditions have also been shown to have an overlap in genetic studies and inflammatory marker studies. Why is that important? Because it may suggest that the current diagnostic categories we use (which then determine the course of treatment) do not accurately represent what seems to be shared underlying biology and, also, some shared symptomatology (for example, a depressed state or problems with cognition can be a feature of all of these conditions).
It is now clear that mental illness affects systems beyond the brain and that gut health may be vital for mental health. Our review and meta-analysis (that is, analysis of the results of all published studies) demonstrated that changes in the gut microbiota are widespread and pointed to some of the most prominent changes that can represent direct or indirect treatment targets for several mental health conditions. However, we have a lot more to learn before specific treatment recommendations can be made.
In recent years, one of the most popular approaches to improve the health of the gut microbiota is probiotics.
The idea of the probiotic (that is, a food supplement containing beneficial bacteria) is by no means new. In fact, one of the earliest scientific reports of probiotics used as a treatment for mental illness came out of the Bethlem Royal Hospital in London in 1910. Following, in the 1920s, numerous probiotics were marketed for their ability to improve mental wellbeing and treat psychiatric conditions. However, this approach was soon abandoned, due to a lack of scientific understanding of the underlying mechanisms.
Now that probiotics are back in the spotlight (as indeed, many studies over the past few years have shown them to improve anxiety, stress, depression, etc.), we must make every effort to understand their mechanism of action and answer some key questions. For example, what is the optimal dosing, duration, or contents of treatment? Are there any potential side effects?
As a PhD student, I am aiming to do exactly that — I am conducting the PROMEX study to assess how probiotics affect the gut microbiota itself, inflammation, and brain chemistry in people with clinical depression and, in turn, how this impacts the depressive symptoms. I hope that the results of this study, along with other similar studies in the field, will contribute towards a shift in the way we see mental illness by emphasising the role of gut health and nutrition.
This is an important step towards more holistic approaches to prevention and treatment, which will help close gaps that current pharmacological treatments alone cannot.