Food For Mood: An Insight Into The Link Between The Gut and The Brain

Figure 1: Food and Drink. Reprinted from Red [1].

The 20th century saw the rise in Freudian theories alongside the introduction of neurochemistry altering antidepressants. This created the prevailing narrative that the root of depression is confined to the realms of the brain. However, prior to neuroscientific theorems becoming the focus of psychiatric research, 19th-century physicians attributed mental health disorders to poor gut health [2]. Blame was directed at the gut rather than the brain. Despite the stagnant interest in the link between the gut and mental illness throughout the last century, this concept has recently re-emerged, with the gut microbiome being the focal point. 

Primarily occupying the colon, the gut microbiome has lived in mutualistic symbiosis with humans for millennia. Collectively weighing more than a human brain, the microbiota is composed of approximately 100 trillion microbial cells (for comparison, that is 10x more than the amount of human cells within the human body and 33x more than the number of trees on the planet) [3, 4]. 

Throughout the last decade pivotal studies in microbiology have discovered surprising relationships between the gut microbiome and mental health disorders. For example, when receiving faecal microbial transplants from patients with major depressive disorder (MDD), germ-free rodents (GF) began to exhibit depressive behaviours. However, no depressive behaviour was displayed in the GF rodents who received microbial transplants from healthy participants [4]. With a myriad of cells in its army, it is not so inconceivable that the microbiota may be capable of manipulating the emotions of sentient beings.

Feed the Army Well

The intestinal microbiome is far from standardised. The microbiota is as individual to a person as their fingerprint. Nonetheless, the composition of the trillions of microbes inhabiting the gut can be somewhat influenced by controllable factors- such as diet. 

From a young age, children become well acquainted with the phrase “eat your 5- a-day”, under the pretence that healthy eating ensures good physical health. Nonetheless, human cells are not the only beneficiaries from a diet high in fruit and vegetables. Some bacterial colonies within the gut feed on the dietary fibres present in fruit and vegetables. The more fruit and vegetables ingested, the more fibre-digesting bacteria are encouraged to grow.

Anaerobic fermentation of dietary fibres via the resident gut bacteria results in the production of molecules called short-chain-fatty-acids (SCFAs) [6]. These molecules are capable of inciting systemic actions around the body. They can enhance the integrity of the intestinal barrier, and importantly, influence the immune system to reduce inflammation [7]. Recently research has alluded to the interconnectivity of depression and inflammation. Studies have found higher levels of inflammatory markers in depressed patients when compared to healthy controls [8]. Additionally, an increased prevalence of depression is exhibited within cohorts with inflammatory illnesses [9]. Randomised control trials have even been able to alleviate and prevent symptoms of depression via prescribing participants an anti-inflammatory diet (most commonly the Mediterranean diet, which encourages a high intake of fruit and vegetables) [10, 11]. Hence, eating “your 5-a-day” may benefit the mind as well as the body. 

Whilst healthy eating may be able to improve mood through means of mitigating inflammation, unhealthy eating may worsen mood through stimulating inflammation. Chronic consumption of foods high in saturated fats can impair the integrity of the intestinal barrier via downregulating the expression of crucial proteins [12]. This permits the translocation of toxins ( lipopolysaccharides, or LPS) from resident gut bacteria across the intestinal barrier.

Once across the barrier, these bacterial toxins bind to receptors on immune cells, activating proinflammatory molecules. The consequence of the proinflammatory molecules reaching the brain is an activated hypothalamic-pituitary-adrenal (HPA) axis [13]. The HPA axis is responsible for the stress response and its activation ultimately results in the release of cortisol (the stress hormone) from the adrenal gland [13]. Studies have demonstrated that people with MDD are more likely to have increased HPA activation and bacterial toxins may potentially be one reason for this [14]. In fact, depressed cohorts have been found to have heightened serum LPS antibody levels and administration of LPS can transiently induce depression and anxiety-related behaviour in healthy participants [15]. 

In addition to indirectly activating the central stress response, the bacterial toxins may also worsen mood by reducing the level of serotonin (the infamous neurotransmitter widely associated with some hypotheses for clinical depression). After being activated via bacterial toxins, the proinflammatory molecules upregulate enzymes responsible for tryptophan metabolism [15]. Tryptophan is an essential amino acid and a precursor for serotonin. The increased tryptophan metabolism results in reduced tryptophan bioavailability. Thus, less tryptophan can cross the blood brain barrier into the brain- diminishing serotonin synthesis [15]. In other words, long periods of unhealthy eating can decrease levels of ‘happy’ neurotransmitters whilst increasing levels of stress hormones. 

In spite of these past statements, the link between the gut and the brain is bidirectional and unhealthy eating cannot be named as the sole cause for low mood and depression. In states of depression and anxiety, the brain may be able to influence the gut and increase intestinal permeability, thus, deeming the individual more susceptible to LPS translocation. Nevertheless, an unhealthy diet will only exacerbate the LPS translocation, which may worsen the associated symptoms.

Conclusion

This article divulges just a few of the known connections between the gut and the brain. Although mental health is exceedingly complex and a strict causal relationship between the gut, diet and mental illness cannot be affirmed, the importance of gut health should not be undermined within therapeutic intervention.

Pharmaceuticals, as well as harbouring potentially unpleasant side effects, can have limited efficacy for some of the patients prescribed them [16]. Studies mentioned within this article have demonstrated how dietary changes can alleviate symptoms of depression and anxiety for some patients. Of course, individual differences in both the composition of the gut microbiome and mental health disorders indicate that dietary change will not be effective for all patients. However, unlike pharmaceutical interventions, side effects from dietary interventions are likely to be positive. Increasing intake of fruit and vegetables whilst decreasing intake of foods high in saturated fats and refined sugar will aid physiological health. The risk of developing type 2 diabetes, cancer and heart disease will shrink, and of course, the fibre-digesting bacteria residing within the depths of the gut will be overjoyed. 

The importance of good nutrition is cardinal in promoting mental well-being. However, in light of the COVID-19 pandemic, healthy eating has decreased amongst many groups of people [17]. In raising awareness of the relationship between food and mental health, a positive shift in public eating habits can be encouraged, aligning with the SDG’s goals of promoting well-being for all ages. 

Key Definitions

Neurochemistry - Signalling chemicals within the brain such as neurotransmitters. 

Gut microbiome/microbiota - The collective name for the trillions of microbes inhabiting the gut. 

Mutualistic symbiosis - Where 2 different species live in close proximity to each other and both species benefit from this.

Germ free rodents - Lab mice/rats that have been specially raised to not contain any micro-organisms. They are kept in controlled environments to ensure they are not contaminated.  

Anaerobic fermentation - As there is no/very little oxygen in the intestine, bacteria cannot aerobically respire (using oxygen to break down glucose and provide energy for the cell). Instead they use the process of anaerobic fermentation- breaking down molecules from foodstuff  to provide them with energy. This process does not require any oxygen.  

References

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