The gut-brain axis: on the relation between microbial life in our gut and our brain

A healthy gut, a healthy brain

Few people realize how the amount of microbes residing in our gut between the mouth and the end of the large intestine outnumber the amount of human eukaryotic cells by ten to one. This complex ecosystem is formed mainly by bacteria, but also viruses, archae, protozoa and fungi.

Even less known is how gut microbes lays a major role in host health by shaping the development of the immune system, metabolizing dietary nutrients (such as fatty acids, glucose and bile acids) and drugs, digesting complex indigestible polysaccharides and synthesizing vitamins and bioactive molecules.

Throughout different life stages, various changes occur in the microbial diversity of humans.
While babies are massively 'inoculated' with microbes from their mother during birth, smaller amounts enter the baby's gut via the bloodstream and placenta.
After birth, the composition of the gut microbes in the infant changes slowly with age, and stays mostly the same until old age.

While the composition of the gut microbes don't change much in a healthy adult, that is not to say that they aren't vulnerable to outside factors, such as lifestyle, use of antibiotics or even vaccinations, and overall health.
However, outside those factors, diet is one of the most important factors for gut health.
A change in a diet, especially by eating more or less fiber can change the composition of the gut microbitics within a few days. When this change is negative, a dysbiosis can result, characterized by an overgrowth of potentially pathogenic organisms.
This change in the delicate balance between 'good' and 'bad' organisms will result in a 'leaky' gut because of a more porous gut lining and cause chronic inflammation, which can even influence our brain because it also affects our central nervous system. So, as incredible as it sounds, an unhealthy diet can cause you to have an unhealthy brain as well.

This makes it easier to understand why an increasing amount of people try to improve gut health.

How does diet influence intestinal flora?

The human gut harbours over ten thousand species of microorganisms, which require a wide array of nutrients and energy sources for normal microbial growth and function. A lack of diversity in a diet and reduced intake of essential nutrients can limit microbial growth and contribute to intestinal dysbiosis.

In the past 50 years our Western diet has undergone major changes, with increased intakes of fatty junkfood and refined refined sugars and diminishing intake of nutritious fiber. As if this isn't bad enough, the bowels will also have lower motility due to a sedentary lifestyle, resulting in the aforementioned dysbiosis and inflammation disorders, such as cardiovascular disease, obesity, depression, allergies, diabetes and autoimmune disorders.

Factors that have a beneficial effect on the composition of the intestinal flora prove to be a high intake of fiber, vegetables, fruits, omega-3 (fish) and mono-unsaturated fatty acids (nuts, olive oil).
A too high intake of fats and meat has been associated with an adverse effect of gut health.
For those on a low-carb diet (e.g. a keto or Paleo diet), it is reassuring to know that shifting the balance of dietary fats towards more conjugated linoleic acid (CLA as present in dairy) and short chain fatty acids (MCT as present in dairy butter or coconut oil) reverses the negative effects of a high-fat diet.

While research shows how a vegetarian or even a vegan diet is superior to the regular Western diet when it comes to the composition of the intestinal flora, a high protein diet isn't the villain it is said to be.
Apparently, athletes who are in need of a high protein diet to recover faster and grow more muscular, are not experiencing the bad effect of a high protein intake in the same way as people do who are living a sedentary lifestyle.

Gut-brain communication

Apparently, diet largely determines the health and composition of our gut. The reverse is also true in the sense, that the composition of our gut determines what and how much the host is capable to extract from its diet, like the type and amount of vitamins and short-chain fatty acids (SCFA) as well as other molecules synthesized by the intestinal flora.
Many of these molecules such as serotonin and gamma-aminobutyric acid (GABA), directly influence the enteric nervous system (ENS). Due to the connection between the enteric and central nervous system (CNS) these molecules also influence brain function and behaviour.

This gut–brain axis, the bidirectional communication system between the gut and the CNS, plays an important role in signals sent between the two nervous systems (ENS and CNS), hormones and immune system.
Through this complex network the gut can influence the brain via visceral messages, and conversely, the brain is able to influence gastrointestinal functions.
The interplay between the gut and the brain is extremely complex, but suffice to say that both diet and the composition of the intestinal flora influence how it functions.
One of these factors that are influenced by the intestinal flora is body composition, as the composition of the intestinal flora may cause an increased energy intake, and by consequence lead to weight gain and obesity.

The human intestine also acts as an endocrine (hormonal) organ through direct and indirect production of microbial metabolites and neurometabolites such as short chain fatty acids (SCFAs), vitamins and neurotransmitters, which have also been shown to influence gut–brain interactions.
GABA and serotonin are neurotransmitters that can influence host behaviour and are produced directly or indirectly by certain microbes. Short Chain Fatty Acids (SCFAs) including butyrate, propionate and acetate can modulate brain functioning, in particular appetite regulation.
Due to the gut-brain axis, it no longer seems so strange how a change of diet and subsequent change of intestinal flora, can improve symptoms of psychiatric illnesses.

A dysbiosis of the intestinal flora has been linked to a number of psychiatric disorders.

Probiotic supplements

A number of studies have reported certain probiotic strains, primarily Lactobacillus and Bifidobacteria, to enhance brain function. So, there is potential for ‘psychobiotics’ (live organisms that benefit psychiatric health).

Many studies have shown a clear association between the intestinal flora and behaviour. Given that the intestinal flora is affected by diet, the composition of the diet may be a crucial factor to a behaviour change.

Due to changes in the Western diet with less fiber and more junkfood, microbial dysbiosis will occur, leading to impaired cognition.

Mental decline is increased by obesity, which may be in part regulated by gut microbiota dysbiosis.

Another factor that will lead to depressive-like behaviour and gut dysbiosis is a lack of magnesium in the diet. Magnesium deficiency will lead to decreased bacterial diversity and anxiety-like behaviour.

In a number of studies, they looked at the effect of prebiotics on psychological disorders.
A 3-week week supplementation with a GOS prebiotic, which stimulates bifidobacterial growth, significantly reduced waking cortisol response, a stress hormone strongly linked to anxiety and depression.


It is evident that there are a number of major metabolic, endocrine and neural pathways connecting the gut and the brain. Indeed, the trillions of microbes and microbial by-products within the gut contribute to the plasticity of these pathways.

Relatively little is known about the extent to which bacterial metabolites can influence brain function.
In addition, the complexity of the pathways involved in the gut–brain axis contributes to the difficulty of identifying true mechanisms of action.

Diet has a suprisingly large impact on the intestinal flora and by consequence, a change of diet can have beneficial effect on both the instestinal flora and cognitive function.

Prebiotics and other larger dietary interventions, including dietary fats and polyphenols also pose potential to alter the gut–brain axis.

Our comment

It is amazing to see how the intestines, that we never identified as having a brain of their own, are as a matter of fact our 'second' brain.
A second brain we can influence by eating a healthier diet with more fiber and beneficial probiotics.

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