The Gut-Brain Axis: More Than A Gut Feeling

The gut microbiome refers to the fascinating ecosystem residing within our digestive tracts – the microbes (e.g. bacteria, yeasts, viruses, archea and fungi), along with their collective genetic material present and the by-products that they produce (e.g. short-chain fatty acids, SCFAs). Research suggests that an optimal gut microbiome is diverse, stable, and resilient.¹ 

Can you remember a time you had “a gut feeling” or felt “butterflies” in your stomach?  

These are real-life examples of your gut-brain axis at work – the bi-directional relationship between the gut and the brain. These two organs are in constant communication with each other. An essential part of the gut-brain axis is the vagus nerve which physically connects the gut and the brain and serves as the main communication channel.^2,3 Other pathways include endocrine, immune, metabolic and neurological signalling.^4,5 The gut microbiome is part of these communication pathways but our understanding is still evolving as research continues to emerge.   

Understanding this gut-brain connection could open exciting underexplored therapeutic avenues. For example, irritable bowel syndrome (IBS) is now recognised as a dysregulation of the gut-brain axis.⁶ Those struggling with IBS have a threefold increased likelihood of anxiety and depression,⁷ and gastrointestinal (GI) symptoms often worsen during periods of stress and/or anxiety. Therefore, when advising patients with IBS, it is important to consider not only dietary interventions but also mental health support, such as cognitive behavioural therapy (CBT) or even meditation or breathwork. 

Could understanding the gut-brain axis be the missing key for your patients to alleviate certain symptoms and help regain control of some of their gut problems and associated  mental health concerns? 

Whilst it’s commonly said that the gut is the “second brain”, this is not entirely true. The “second brain” is actually the enteric nervous system (ENS) – a network of around 500 million neurons embedded along the GI tract. The ENS is a large unit of the peripheral nervous system (PNS) that can control GI behaviour independently of the central nervous system (CNS) input. It is the ENS which connects to the vagus nerve² and communicates with the brain via several neuromodulators and neurotransmitters, as well as via microbial metabolites such as short-chain fatty acids (SCFAs).³ 

You may have heard that around 95% of serotonin (dubbed our “happy hormone”) is produced in the gut,^8,9 and this is often offered as an explanation of how gut health can benefit the brain. 

While this is true, it doesn’t tell the full story. The serotonin produced in the gut is unable to cross the blood-brain barrier and exert a direct effect on the brain.¹⁰ Despite this, it seems reasonable to suggest that gut-produced neurotransmitters such as serotonin may still indirectly influence mood via the immune system and vagus nerve.  

Tryptophan, however, (an essential amino acid and the precursor molecule for serotonin) can cross this blood-brain barrier and modulate serotonin production and function in the brain.¹¹ Interestingly, research in a depressed mouse model has shown reduced levels of tryptophan in faeces which correlated with significantly decreased levels of faecal Lactobacillus.¹² The exact mechanisms by which our gut microbes can modulate our mood is an active area of research, however it’s known they can metabolise tryptophan.¹³ Tryptophan is also found in foods such as poultry, oats, bananas, dried prunes, milk, tuna fish, cheese, bread, peanuts and chocolate.¹¹ 

To date, most gut-brain research has been conducted in animal models, while the limited number of human studies have focused on psychiatric conditions. 

It is clear that diet can impact mental health as shown in the landmark SMILES trial where consumption of a modified Mediterranean diet resulted in reduced anxiety and depressive symptoms compared to the control group receiving social support only.¹⁴ However, mechanisms of action (e.g. gut microbiota composition) were not measured and thus remain unknown. 

Interestingly, when the gut microbiome from depressed individuals was transferred into rats (known as a faecal microbiota transplant), these rats then displayed depressive symptoms¹⁵; thus suggesting a causal role of the gut microbiota in the development of depression. 

Observational evidence also shows people living with conditions such as autism,^16,17 Alzheimer’s disease,^18,19 Parkinson’s disease^20,21 and psychiatric stress disorders^22,23 display gut dysbiosis (imbalance) and often live with GI symptoms before and after diagnosis.  

When it comes to anything to do with gut health, it is all about taking it back to basics. The below are fundamental to optimising the gut-brain connection and are the real game-changers of health. 

1. Diet: Focus on the two F’s – fibre and fermented foods/drinks. Encourage patients to prioritise eating fruit, vegetables, wholegrains, nuts and seeds as well as fermented foods such as kimchi, kombucha, sauerkraut and fermented milks (ensuring they contain live bacteria). Following a Mediterranean diet, rich in omega-3 fatty acids, vitamin D and polyphenols, has also been shown to help in the prevention and treatment of certain mental conditions, including depression.²⁴
2. Psychobiotics: This term now extends beyond merely the application of probiotics for mental health benefits, and includes any exogenous influence whose effect on the brain is bacterially-mediated. Certain live microorganisms such as probiotics may offer mental health benefits when used as an adjunct treatment in mental disorders such as depression. This is an active area of research (alongside prebiotics and synbiotics) however promising research in human trials is emerging.^25-27 
3. Exercise: Exercise is a powerful stress reliever, reducing anxiety and improving mood thanks to the release of ‘feel good’ neurotransmitters such as dopamine, serotonin and endorphins. Exercise is also shown to increase the diversity and growth of beneficial bacteria in the gut independently of other factors.²⁸ 
4. Sleep: Sleep is essential for managing stress levels and supporting the gut-brain axis.²⁹ Recommend aiming for 7-9 hours of quality sleep each night to support the body’s daily recovery and maintain balanced stress hormones. Sleep disruption can disturb the circadian rhythm, impacting the balance of beneficial and harmful gut bacteria.²⁹
5. Stress management: Managing stress is crucial for maintaining a healthy mind and body. Chronic stress leads to elevated cortisol levels which can lead to anxiety, mood disturbances and low self-esteem, as well as affecting gut health by upsetting the balance of the gut microbiome.³⁰ Encourage patients to incorporate mindfulness techniques such as breathwork, walking in nature or yoga. 

The gut-brain axis is an incredibly exciting area of research, but there is still so much unknown about this complex two-way communication network. As research continues to advance, it is hoped that we can identify which specific brain conditions may benefit most from gut microbiome-targeted interventions, and vice versa. There is also a need to better understand mechanisms of action. Deepening our understanding of the gut-brain connection has the potential to revolutionise both gastrointestinal and neurological/mental health services; transforming prevention strategies and treatment options. 

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