The Gut-Brain Axis: the two-way street of physical and mental health
8th February 2024 - Last modified 4th July 2024
By Dan Birkinshaw, science writer.
Once thought to be entirely separate, our digestive systems and mental well-being are in fact intrinsically linked. The last decade of research has cemented this ‘gut-brain axis’ in the medical mainstream and helped to improve our understanding of how our gut health, and specifically our gut microbiome, can impact our mental health. But this is not just a one-way street. Read on to discover how our mental health may also have a pronounced effect on our gastric physiology!
A vicious cycle
The modern world can be an incredibly stressful place for a lot of us, and that stress can take many forms. From the ongoing pressures of constant daily chores, rent or mortgage payments and impending deadlines; to more severe acute episodes brought on by extreme events and the post-traumatic stress that can follow, we all experience stress throughout our lives.
If you have ever experienced a mental health condition and/or a gastroenterological one, you may be all too familiar with the cyclic nature of these maladies…
It’s the morning of an important work meeting, your anxiety kicks in, which in turn sets off a bout of stomach cramps. As the meeting fast approaches, those cramps are causing more stress as you worry about the effect this gastric pain will have on your performance in front of your team.
By understanding how this vicious cycle begins and feeds itself, we can find a way to break free from it.
A gut feeling
We have known for a long time that our gastric health can have knock-on effects on our neurological development and mental well-being [1]. The NHS reports that mental health conditions are increasingly prevalent, with one in every four adults suffering from ‘probable mental health disorders’ in any given year [2]. Gastrointestinal disorders are also becoming increasingly widespread, with as many as one in five adults in the UK affected by irritable bowel syndrome (IBS) [3] and over one in every 123 suffering from some form of inflammatory bowel disease (IBD) [4].
Changes in the makeup of our gut microbiomes – the various commensal microflora in our digestive systems – can have pronounced effects on neurology and mental health. The effects of these essential bacterial companions cannot be overstated, with links to neurological conditions, such as Parkinson’s disease and autism spectrum disorders [5]; as well as chronic mental illnesses such as depression [6], obsessive compulsive disorder (OCD), and generalized anxiety disorder [7].
It goes both ways
The gut-brain axis comprises many pathways which take several distinct forms. These pathways can be structural, for example the neurons of the central nervous system (CNS); chemical, such as neurotransmitters and endocrine hormones; or cellular, as in immune response inflammatory pathways [8]. All of these component pathways can be mediated by our gut microbiomes, but our understanding of them is starting to reveal that this might not be the one-way street we once thought, and that these myriad pathways are, in fact, bi-directional.
This presents a potential new frontier for the treatment of gastrointestinal conditions in conjunction with mental health conditions. Changes to the gut microbiome may, in fact, be influenced or even instigated by fluctuations in mental well-being [9].
Stress has been shown to induce widespread maladaptation of the gut microflora, resulting in increased gastrointestinal disorder and disease susceptibility. This leads to the exciting possibility that by tackling mental health conditions we can also provide relief from gastric distress [10].
Everyone that endures a neurological or mental health condition experiences it in a unique way. Tolerances to stresses and triggers are highly individual, and so is the composition of our gut microbiomes [11]. Stress, anxiety, depression, and OCD can all trigger dysregulation of these microflora [9], and we can observe distinct patterns in this dysbiosis for all of these conditions [12].
Treatment of an imbalanced gut microbiome cannot be a matter of ‘one size fits all’ [13], and neither can the treatment of mental health conditions.
A two-pronged attack
Flare-ups in gastroenterological conditions like IBS and IBD can be triggered by ill mental health and cognitive stress, as can inflammatory responses throughout the body. Chronic and traumatic stress are particularly guilty of causing such episodes [9]. These inflammatory responses involve immune activation [14], and medications commonly used as antidepressants have previously been shown to reduce the inflammation. However, in cases where the immune response is more pronounced, the effectiveness of this treatment is diminished [15].
So how can we harness the gut-brain axis to treat gastric conditions? One answer may be hidden in our genes!
Co-expressed gene pairs involved in the pathology of many neurological and gastric diseases have been identified across the entire human genome [16]. This tells us that these diseases and their pathologies are interlinked at the genetic level. Simultaneous treatment of neurological and physiological disease may very well be a possibility if we can manage the co-expression of these genes, for example through targeted gene silencing.
Breaking the cycle
So, how can we utilize the gut-brain axis to escape the cycle of ill mental health and gastric distress? By understanding the bi-directional pathways and identifying the personalized response that best fits the patient.
Medical intervention can target the brain via the gut, and now we know that we can target the gut via the brain. In both cases, the microflora are essential. For example, the metabolites absorbed when our microflora break down flavonoids can cross the blood-brain barrier (BBB) and accumulate in the CNS to convey neuroprotection [17]. Similarly, changes in neurotransmitter release and reabsorption in the brain can lead to dysbiosis in the gut [18].
By employing an approach that simultaneously addresses brain chemical imbalances and gut microbiome dysbiosis, it may be possible to break the cycle in two places at once.
A personalized approach
The gut brain-axis is an intriguing avenue for future medical research and the treatment of a wide range of conditions. Though once thought to operate exclusively from gut to brain, the fact that it simultaneously operates from brain to gut creates exciting new opportunities in mental and gastric health care. By alleviating stress, depression, and anxiety we can influence the gut microbiota to break the vicious cycle of mental and gastric distress.
Further research into the genetic components of these conditions could illuminate pathways to treat concurrent mental and gastric illnesses. With these aspects of the gut-brain axis combined, medical professionals will be able to provide patients with more holistic and personalized treatments for these often life-limiting conditions.
Suddenly, that big meeting doesn’t seem so scary after all.
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References
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2. Adult and older adult mental health. NHS England.
3. Irritable Bowel Syndrome. (2023, August). BUPA.
5. Costa, M. A., Doifode, T., Gonçalves, C. L., et al. 2024. The many faces of microbiota-gut-brain axis in autism spectrum disorder. Life Sciences, 337, https://doi.org/10.1016/j.lfs.2023.122357
6. Cryan, J.F., Donoso, F., Nolan, Y. M., and Olavarría-Ramírez, L. 2022. Inflammation, Lifestyle Factors, and the Microbiome-Gut-Brain Axis: Relevance to Depression and Antidepressant Action. American Society for Clinical Pharmacology and Therapeutics, 113(2) 246-259
7. Baker, G. B., Durson, S. M., MacKay, M., and Yang, M. 2024. The Gut-Brain Axis and the Microbiome in Anxiety Disorders, Post-Traumatic Stress Disorder and Obsessive-Compulsive Disorder. Current Neuropharmacology, 22(5) 866-883
8. Keshavarzian, A., Manfready, R. A., and Post, Z. 2023. Overview of the Gut–Brain Axis: From Gut to Brain and Back Again. Seminars in Neurology, 43(4), 506-517
9. Kim, Y. and Lee, Y. 2021. Understanding the Connection Between the Gut–Brain Axis and Stress/Anxiety Disorders. Current Psychiatric Reports, 23(22), https://doi.org/10.1007/s11920-021-01235-x
10. Clarke, G., Cryan, J. F., Gheorghe, C. E., et al. 2023. The impact of acute and chronic stress on gastrointestinal physiology and function: a microbiota–gut–brain axis perspective. The Physiological Society, 601(20), 4491-4538
11. Blaser, M. J., Caporaso, J. G., Gilbert, J., et al. 2018. Current understanding of the human microbiome. Nature Medicine, 24, 392-400
12. Abyad, A., Candan, E., Ceylan, A., et al. 2023. Depression Causes Various Inflammatory Processes in Human Body. HSOA Journal of Gastroenterology and Hepatology Research, 7(42), http://dx.doi.org/10.24966/GHR-2566/100042
13. Keshavarzian, A., Manfready, R. A., and Post, Z. 2023. Overview of the Gut–Brain Axis: From Gut to Brain and Back Again. Seminars in Neurology, 43(4), 506-517
16. Gong, W., Guo, P., and Li, Y. 2022. Role of the Gut-Brain Axis in the Shared Genetic Etiology Between Gastrointestinal Tract Diseases and Psychiatric Disorders: A Genome-Wide Pleiotropic Analysis. JAMA Psychiatry, 80(4), 360-370
18. Marano, G., Mazza, M., Lisci, F. M., et al. 2023. The Microbiota–Gut–Brain Axis: Psychoneuroimmunological Insights. Nutrients, 15(6), https://doi.org/10.3390/nu15061496