Do you get butterflies in your stomach when you get nervous or anxious? Ever wondered why this happens? Turns out your gut could play a larger role in your mood than you thought. In recent years’ scientists have been linking disturbances in gut bacteria to several various conditions; including Parkinson’s disease, allergic reactions and depression (Evernsel and Ceylan, 2015).
Mice that are raised in a completely sterile or “germ-free” environment develop an overactive Hypothalamus-Pituitary-Adrenal (HPA) axis (Sudo et al. 2004). This axis is involved in controlling the release of certain neurotransmitters and hormones, including the stress hormone cortisol. Exposing the gut of these mice to certain bacteria leads to recovery of normal function of the HPA system. It is therefore suggested that the bacteria in the gut – or microbiota – can alter the development of their brains. These mice were also found to have altered neurotransmitters such as noradrenaline and serotonin, known to influence mood.
Figure 1 Visual demonstration of how the gut bacteria can influence brain activity. Taken from: http://sanjosefuncmed.com/successful-aging-part-8b-gut-connections-organs/
In patients that suffer from major depressive disorder, an altered HPA axis has been observed (Dinan and Cryan, 2013). For example, patients often have higher levels of the stress hormone cortisol. Current antidepressants work by changing the levels of noradrenaline and serotonin in the brain. If you link this with the evidence that the bacteria in the mice gut could alter these neurotransmitters, you can hypothesise that altered gut microbiota in humans could cause depression (Figure 1). Alternatively, altering the gut bacteria could potentially treat depression.
The next step for neuroscientists is to actually prove that altered gut microbiota can cause depression or vice versa (Figure 1). Park et al, 2013 used a mouse model of depression to examine HPA alterations and gut microbiota. The mice that presented with chronic depression-like and anxiety-like behaviours also had an elevated HPA axis (and therefore an elevated stress response), and altered gut flora as well as gut motility. These same effects could be brought about by direct administration of corticotropin-releasing hormone.
A proposed theory is that chronic stress causes increased levels of stress hormones from the HPA axis. This can act on the gut to alter bacterial levels and distribution, altering motility and causing diseases such as Irritable Bowel Syndrome (IBS). This further disturbs gut bacteria that can then feedback to the brain, potentiating the stress-response, leading to a cycling that could result in depression. These gut disturbances could explain why patients with IBS also often suffer from depression (Park et al, 2013). The feedback from the gut to the brain is proposed to be brought about by the immune system through activation of inflammatory chemicals that can travel in the blood to act on the brain (Dinan and Cryan, 2013; Figure 1).
Whilst it is easy to get excited about a new possible, effective treatment for depression (something we are sorely lacking), we must bear in mind that these links between gut microbiota and depression have only been shown in preclinical animal models, and the findings are yet to be replicated in humans. It is also still being examined whether the changes in gut bacteria are a primary cause, or a secondary effect from depression. However, full research may lead to the potential of probiotics being used to treat depression (Dinan and Cryan, 2013).
Author: Rosie Porter
Editor: Molly Campbell
Evrensel, A. and Cevlan, M.E. (2015) The Gut-Brain Axis: The Missing Link in Depression. Clinical Psychopharmacology and Neuroscience. 13(3): 239-244
Dinan, T.G. and Cryan, J.F. (2013) Melancholic microbes: a link between gut microbiota and depression? Neurogastroenterol. Motil. 25: 713-719
Park, A.J. Collins, J. Blennerhassett, P.A. Ghia, J.E. Verdu, E.F. Bercik, P. and Collins, S.M. (2013) Altered colonic function and microbiota profile in a mouse model of chronic depression. Neurogastroenterol. Motil. 25(9): 733-741
Sudo, N. Chida, Y. Aiba, Y. Sonoda, J. Oyama, N. Yu, X.N. Kubo, C. Koga, Y. (2004) Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol. 558(1): 263-275