The Gut-Brain Highway: What Does It Mean for the Future of Mental Health Treatment?

The Gut-Brain Highway: What Does It Mean for the Future of Mental Health Treatment?

Can your gut tell your brain how to feel? Well, in the last 10 or so years it has become increasingly clear that the health of gut is intrinsically linked to our emotions and mental health. More specifically, it is the intestinal microbiota which communicate with our brains as to the health status of our gut and vice versa.

It has been known for a long time that our gastrointestinal tract communicates with our central nervous system, but more recently evidence has demonstrated how the gut flora, made up of microorganisms, interacts with our brains.

The communication between the gut and brain is bi-directional and can be achieved via various pathways including neural, endocrine, immune, and humoral. This communication between the gut microbiota and human immune cells often occurs via toll-like receptors (TLRs; proteins that recognise all non-self-substances) and also pattern recognition receptors (PRRs; recognise patterns in pathogens that enter our body). When damage to the gut microbiota occurs, such as through bad diet or inappropriate antibiotic use, they can then influence these TLRs and PRRs to release messages to our immune cells to initiate an inflammatory response.

This immune activation includes the activation of the hypothalamic-pituitary-adrenal (HPA) axis, which then coordinates the release of corticotrophin-releasing factor and cortisol. These compounds then activate the release of inflammatory compounds called cytokines, which can affect, among many things, gut function.

If the HPA axis fails to shut off after immune activation it can cause the continual release of these inflammatory cytokines. While these inflammatory processes are critically important for eradicating the body of foreign substances, when they are overactivated, or remain in a chronic level of activation, they can be harmful.

This dysfunction can be a perpetual cycle, with chronic stress potentially leading to alterations in the functionality of the HPA axis, which can lead to altered inflammatory activation and therefore gut function. The dysregulation in the functioning of the gut flora, or microbiota, has been linked to many autoimmune diseases such as inflammatory bowel disease (i.e., Crohn’s disease), irritable bowel syndrome, and metabolic syndrome to name a few.

There is an established link between low grade, chronic inflammation and mental health and it is well-known that our stress hormone, cortisol, released during the activation of the HPA axis, is commonly dysfunctional in anxiety and depression. Therefore, it makes theoretical sense that if there is inflammation in the gut, which can travel to other areas of the body, such as the brain, that there would be an increased risk of mental health issues.

The research linking the gut microbiota and mental health is in its infancy, but there are some intriguing results in animal models. Differences in the richness and diversity of the microbiota has been demonstrated to be linked with mental health status. Links have also now been established suggesting a comorbidity between psychiatric disorders (anxiety and depression) and gastrointestinal problems, so much so that the degree of psychiatric illness can predict later onset of a functional gastrointestinal disorder or vice versa.

Let’s look at a few of intriguing avenues of current research: faecal transplants, diet manipulation, and cognitive behavioural therapy (CBT).

Faecal transplants

It might sound awful and far fetched, but faecal transplants have begun to gain traction as a genuine treatment for a multitude of diseases and disorders. In relation to mental health there remains limited evidenced-based research to the efficacy of faecal transplants; however, initial, small scale, animal model studies look promising. Evidence in rats has demonstrated that transferring faecal matter from clinically depressed humans into the gastrointestinal tract of rats results in the rats developing both behavioural and physiological signs of depression.

Aside from faecal transplants other gut-focussed research in animal models has demonstrated in a mouse model that anxiety-like behaviour and depressive symptomology levels after administration with a probiotic were reduced. This study also included a human randomised control trial which demonstrated reduced self-reported stress levels and free cortisol levels in people who had taken a probiotic.

Diet

The Western diet (high in fat) and an increased risk of developing a mood disorder has been shown, with mice eating a high fat diet demonstrating an increased risk of developing anxiety-like behaviour and depressive-like symptomology.

Conversely, evidence from animal models shows us that by limiting the total number of calories we consume can reduce anxiety levels and brain inflammation. This may not be a complete solution, but by harnessing some of the theorised mechanisms that have been suggested through this research may be a further avenue of investigation.

Evidence is emerging from randomised controlled trials of the importance of a good quality diet in the treatment of mental health issues. Nutritional psychology has grown in momentum, which is the study of how nutritional choices can impact on general health measures, including mental health. And let’s not forget psychobiotics, which is looking at how your gut microbiota health can affect your neurochemistry and mental health.

CBT

There is even emerging evidence that behavioural treatments for mental health may be able to help with gastrointestinal issues. We’ve long known we can’t separate our emotional/mental health from our physical health. So, something as simple as what we eat having an impact on how we feel makes sense.

Outside of the microbiota per se there is some interesting research to demonstrate the efficacy of CBT in lowering circulating inflammation levels (C-reactive protein) in elderly patients. We could postulate there may be similar results when looking at CBT and the effects of chronic inflammation and the microbiota. There are a few clinical trials underway, but more, evidenced-based research clearly need to be done.

The gut-brain highway may be a chicken and egg scenario – Is the gut and microbiota dysfunctional and therefore changes are seen in the brain, or are there issues in the brain which are causing the dysregulation in the microbiota? There is currently evidence for both ways, meaning the answer is most likely that both the chicken and egg are correct.

Learning more about the role the gut microbiota plays in our mental health will lead a multimodal approach to treating mental illness. It won’t be a complete answer, but if we add this to what we already know, then we dramatically increase the opportunities and options for mental health treatment.


Leah Kivivali is Postdoctoral Research Fellow in neuroscience at La Trobe University in Melbourne and obtained a PhD in neuroscience from La Trobe University. Leah has a wide and varied experience ranging from bench science and neuroscience to public health, mental health, epidemiology, and rare disease and is the author of the Woman in Science blog and tweets via @WomanScience.

 


 

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