Food for thought: the gut-brain axis

By Wang Jia Hua

The proverbial saying “You are what you eat” is one that we are all too familiar with, but it appears that nutrition is not the only dietary factor influencing our mental and physical health. Recent research strongly supports the role of microbial communities in our guts in shaping our brain function, behaviour, and immune regulation. This is not surprising, given how more than half of the human body’s total cell count is non-human and consists of microbes which collectively form the human microbiota. Particularly, the human gut hosts the greatest number and diversity of microbes within the entire body.

The microbial diversity and composition in humans vary across different life stages, and it is posited that we first came into contact with microbes as foetuses. This may occur during birth, or as early as the prenatal period where the foetus is exposed to an initial inoculum of microbes from the mother via the bloodstream and placenta. The gut microbiota is generally established from the second year of life onwards, whereby the intestinal epithelium has developed to tolerate and support the gut microbiota with the help of the mucosal barrier that it secretes. During healthy adulthood, the gut maintains a relatively stable microbiota profile consisting mainly of Bacteroidetes and Firmicutes, until ageing occurs. While these microbial communities are mainly composed of bacteria, they also include archaea, viruses, protozoa and fungi.

A myriad of factors determine the microbiota profile of each individual – which results in personal microbiomes that can potentially act as fingerprints to uniquely identify individuals. Some factors are innate and hard to change, such as host genetics and health status, while others can be modified by our lifestyles. These include personal hygiene, use of antibiotics and vaccinations, stress levels, and most importantly, diet. Notably, dietary changes are shown to be related to over half of the variations in the gut microbiota, with major changes taking place within a matter of days. In fact, past studies have classified human gut microbiomes into 3 distinct enterotypes which are tightly linked to diet and eating habits. These enterotypes are based on clusters of dominant bacterial communities, namely Bacteroides (enterotype 1), Prevotella (enterotype 2), and Ruminococcus (enterotype 3). However, this classification is now perceived to be controversial due to the highly dynamic and complex nature of the gut microbiota.

In a healthy gut, trillions of microbes play a vital role in host health. Some of these microbes establish not only a commensal relationship with the host,  but also a mutualistic one where both benefit. For example, they are responsible for degrading complex indigestible dietary polysaccharides and synthesizing essential vitamins (e.g. vitamin B, K) and amino acids. They can also metabolize dietary nutrients (e.g. bile acids, fatty acids) and drugs. Gut microbiota also have a key role in eliciting innate immunity against pathogens by acting as biological barriers and creating a hostile environment for foreign bacteria. This can be achieved by secreting toxic substances or by competing for nutrients or attachment to cell surfaces.

Generally, a healthy gut microbiota is characterised by a large taxonomic diversity of over ten thousand species. As different species have different nutritional and energy demands for growth and development, any dietary imbalances or disruptions could result in a state of dysbiosis. This could be caused by an overgrowth of pathogenic species and/or a depletion in beneficial ones. Dysbiosis is a key cause of ‘leaky gut’, or high intestinal permeability, where tight junctions of intestinal linings become damaged, allowing large undigested food particles and intestinal microbes to traverse the weakened linings and enter the bloodstream. These particles are viewed by the immune system as foreign bodies which trigger immune responses that are associated with certain inflammatory and immune-mediated disorders. It is worth noting that the concept of leaky gut, and its effects beyond known gastrointestinal conditions, is still rather speculative. 

Apart from nutrients, our gut microbiota is also able to extract bioactive signalling molecules from our diet. These include neurometabolites, vitamins and short-chain fatty acids, of which many are involved in neural signalling within the enteric nervous system. Bidirectional communication between the gastrointestinal system and the central nervous system occurs via the gut-brain axis and can also be modulated via microbial metabolites produced in the gut. As such, there are many avenues for our gut microbiota to influence our brain function and behaviour. 

Particularly, studies have shown that our eating behaviour could be manipulated by the microbes within our gastrointestinal tract. For example, human neurotransmitters such as dopamine and serotonin are directly and indirectly produced by certain microbes to possibly reward the eating of foods that they specialize on. Toxins are also released in the absence of nutrients, with the effect of altering host mood and appetite. Furthermore, microbes may also alter taste receptor expression and activity to directly influence host eating behaviours.

While these findings are all exciting, the research done in this field is still in its infancy. Hence, they are largely speculative, and few have been translated into human application. Regardless, it is always a good idea to maintain a well-balanced diet as it is still generally associated with good health for both our microscopic residents and us.

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