The relationship between depression and the gut has been the subject of scientific research for many years. It seems that we are talking about two separate relationships here - after all, we associate depression with the brain, and the intestines as part of the digestive system. If you were to ask a group of people what is the leader of the psychological thoughts in our body, most of us would probably point to the brain. Meanwhile, it is suspected that there is another body in us, equally hungry for power and deciding how we feel. We are talking about the intestines, which has recently been called the "second brain", and it has even been hypothesised that the intestines are the location of good and bad moods ^[1]. Where is the connection in all this? Why do we talk about the gut-brain connection, although they are different locations in our body? It turns out that there is something between them that connects, communicates, sends signals and can interact with each other.

What connects the brain and the intestines?

The communication between the gut and the brain is referred to as the gut-brain axis or simply the gut-brain axis. The gut-brain axis is an integrated system consisting of many immune, hormonal and neural elements, through which the brain sends signals to the intestines and the intestines send signals to the brain ^[2]. One of the most interesting aspects of this two-way communication is how and with what the intestines affect the work of the brain, and finally the psyche. Throughout the digestive tract, there are 100-500 million nerve cells located in two thin layers lining, among others, intestinal membranes. For this reason, the intestines are considered to have their own nervous system (ENS = enteric nervous system) ^[3]. In turn, the brain-gut axis is the main communication tool between the enteric nervous system and the central nervous system.

Irritable Bowel Syndrome and Depression

Think of a time when you or someone close to you was facing a difficult exam or an important event in your life and experienced diarrhoea or abdominal pain under the influence of stress. The “gut and psyche” relationship is more complicated than temporary, passing digestive ailments under the influence of a stress factor. Disorders of the brain-gut axis are one of the important causes of irritable bowel syndrome (IBS = irritable bowel syndrome). People with IBS, sometimes under the influence of stress or negative, but also positive emotions, may experience gastrointestinal disorders, regardless of the way they eat ^[4]. Interestingly, disorders within the functioning of this axis are also identified in people with depression ^[5]. Irritable bowel syndrome has a lot in common with depression, moreover, it is found that patients with IBS have a much higher level of anxiety and suffer from depression more often than healthy people ^[5].

The enteric nervous system as an important link for well-being

To confirm the existence of the "gut and psyche" relationship, it is worth paying attention to the nervous system, which is located in the digestive tract. The enteric nervous system (ENS) sends signals to the brain via the vagus nerve. Researchers have found that vagal disorders occur in people with depression.has even been developed vagus nerve stimulation and it is believed that this method can be a supplement to psychotherapy and pharmacotherapy, i.e. the main methods of treating patients with affective disorders or depression ^[6]. Anxiety neurosis also seems to be related to the state of the gut through the action of the vagus nerve ^[7].

Influence of intestinal microbiota on the gut-brain axis

We have much more influence on the functioning of the gut-brain axis than we may think. Important factors determining its work include what is in our intestines, and more specifically the intestinal flora / intestinal microflora. More and more often, however, broader terms are used, i.e. "intestinal microbiota", which is an important link for the proper functioning of the axis. Inside every human being live billions of microorganisms - bacteria, viruses, fungi and other life forms, as well as structural elements, metabolites, signalling molecules and environmental conditions, collectively referred to as the gut microbiota ^[8]. It turns out that the way we eat and the environment we live in significantly affect the intestinal microbiota. Our diet and environment influence the diversity of gut bacteria populations, which mediate i.a. by fermenting dietary fibre in the production of gut-important short-chain fatty acids, endogenous signals that play an important role in lipid homeostasis and reducing inflammation ^[9]. In other words, what we eat affects how diverse our intestines are.
How does this relate to depression and well-being? The gut microbiota is altered in people with mood disorders and plays a role in their formation. Scientists went a step further and recognised that the gut microbiota is in constant two-way communication with the brain through the microbiota-gut-brain axis, and therefore has a lot to say about well-being ^[9]. The latest reports also indicate that the intestinal microbiota can additionally activate the hypothalamic- pituitary-adrenal axis), which is one of the main systems controlling our reactions to stress and involved in the regulation of mood and emotions ^[11].

Gut bacteria and depression

There are 10 times more microbial cells in the human intestine than in the rest of the body. The total number is about 100 billion microorganisms representing as many as 5,000 different species that weigh up to 2 kilograms ^[12]. Is there a relationship between “depression and the gut”? Diversity in the gut microbiota and thus gut bacteria is strongly associated with mood, including depression. This is the result of two-way communication, which is confirmed by the relationship between the gut and the psyche. In the observations of people with depression, it is noted that changes in selected populations of intestinal bacteria may contribute to depression. In addition, it is suspected that depressive states may induce modification of certain species of intestinal bacteria and ultimately contribute to a more severe course of depression. It may also work the other way, as observations in animals may indicate. The microflora of rodents exposed to stress and depression is characterised by a lower diversity of intestinal bacteria ^[13]. Therefore, it is suspected that a poor gut microbiota may contribute to some extent to depression, while the presence of depression itself may reduce the diversity of this microbiota.

Changes in the intestinal microbiota and the level of serotonin

Serotonin, commonly known as the "happiness hormone", belongs to neurotransmitters, i.e. substances secreted by nerve cells, enabling them to communicate with each other. Serotonin is involved in regulating e.g. behaviour, mood, feeling pain and memory, affects the work of the digestive system, and is also responsible for a good mood. reuptake inhibitors (SSRIs serotonin), which is why the interest in the production of this neurotransmitter by our body is so great. It is estimated that as much as 95% of serotonin is produced in the intestines, while only 5% in the central and peripheral nervous system [^14]! Altered amounts of serotonin are found in many mental disorders. Some studies suggest that there is a correlation between the intestinal microbiota and serotonin metabolism, which is why it is suspected that depression may be related to intestinal problems ^[15].

From tryptophan to serotonin

Serotonin, or 5-hydroxytryptamine (5-HT), is made from tryptophan. Tryptophan is an amino acid that should be supplied with the diet. The sources of tryptophan include products rich in protein, i.e. eggs, fish, seafood, meat, legumes, dairy products, nuts, seeds, seeds. Tryptophan is also found in bananas, avocados, whole grains and chocolate. This compound is important not only for the synthesis of serotonin, but also melatonin and niacin. The literature suggests that tryptophan plays a significant role in the proper functioning of the brain-gut axis and the immune system ^[16]. In order to provide the body with the right conditions for the production of serotonin, we should provide min. 0.9g of protein per kilogram of body weight, take care of the intake of tryptophan from the diet and other micro- and macroelements. Magnesium is also needed for the proper metabolism of serotonin in the body. We should take care of magnesium intake by including in our diet: cereal products, legumes, nuts, cocoa, unpasteurised cheese, fish, potatoes, bananas and vegetables ^[17]. This element also affects the metabolic pathways involved in the formation of depression. Nevertheless, the possible role of magnesium in the prevention and treatment of depression remains unclear, although there is some correlation between very low magnesium intake and depression, especially in young adults ^[18,19]. It is also worth mentioning that there is an important element of tryptophan metabolism, from which serotonin is formed. This is the gut microbiota. It turns out that the microbiota metabolises tryptophan to bioactive compounds that can affect the brain and our behaviour ^[20]. Therefore, in order to support mental health and well-being, we should focus on taking care of the intestinal microbiota.

What diet is bad for the gut microbiota?

One of the most important elements determining how our microbiota will look is the way we eat, i.e. diet. The “Western” diet has a negative impact on the diversity and populations of the microbial species that make up the gut flora. Unfortunately, this meat-sweet diet is the diet of many of us, and more precisely, it is a diet rich in animal protein, saturated fatty acids and salt, low in dietary fibre, vegetables and fruits, as well as rich in simple sugars and processed carbohydrates ^[21]. This diet has been linked to cognitive impairment, emotional disorders, as well as depression, metabolic syndrome, and neuropsychiatric disorders ^[22,23].
A diet similar to the Western diet with the telling abbreviation "SAD", was also considered a diet harmful to the psyche. The SAD diet, i.e. the Standard American Diet (SAD) has a pro-inflammatory effect. Chronic inflammation is a feature of almost all neurological and neurodegenerative disorders, including anxiety, neurosis and even depression. People with anxiety disorders have been found to have elevated levels of inflammatory markers in their blood and cerebrospinal fluid. The most damaging elements of the SAD diet that are claimed to increase inflammation are processed carbohydrates and processed vegetable oils. It is suspected that this diet may increase the production of advanced protein glycation products in the brain, contributing to neuritis, metabolic diseases and mental deterioration^[24,25].

What diet is conducive to intestinal microbiota and improves mood?

The relationship between “diet, depression and gut problems” is still a controversial topic. Unfortunately, there is no specific diet that can cure depression or anxiety, but fortunately, we can support our gut microbiome, which has an impact on our well-being. Some nutritional interventions have also been identified that may reduce the risk of mood swings and even depression. Such diets include the Mediterranean diet and the DASH diet ^[26,27]. Recent reports suggest that a beneficial diet is also the MIND diet, which is a hybrid of the Mediterranean diet and the DASH diet, which may reduce the likelihood of depression ^[28]. Finally, the anti-inflammatory diet deserves attention, which in the 2019 meta-analysis was recognised as a potentially effective intervention and preventive measure reducing the risk and symptoms of depression ^[29]. All these diets have many common features that will help rebuild the intestinal bacterial flora, positively affecting the mood and well-being.

How to rebuild the intestinal bacterial flora, and more specifically the intestinal microbiota?

First - the variety of food products

The correct intestinal microbiota is conditioned by the variety of food products consumed. In simple terms, this means that the more diverse low-processed food products land on our plate, the more diverse our intestinal microbiota is, which is a very desirable phenomenon ^[30]. At the same time, the more we eat monotonously based on the same food products, the more we expose our microorganisms living in the intestine to unfavourable quantitative changes, which negatively affects the brain-gut axis and thus may worsen our well-being.

Second - fibre

High intake of dietary fibre modifies the intestinal microbiota acids (SCFA -chain fatty), which are extremely important for intestinal health ^[31]. These acids can also stimulate intestinal cells to increase the production of serotonin. It is also suspected that SCFAs may play an important role in stress-induced disorders, anxiety disorders and depression ^[32]. Products rich in fibre are vegetables, fruits, whole grains such as groats, rice, flakes, bran, dark pasta, but also legumes.

Third - prebiotics

Prebiotics are substances that selectively stimulate the activity or growth of selected strains of bacteria in the intestine. In addition, these substances can positively influence the value pH in the intestine, and also have a positive effect on the absorption of certain nutrients. In addition to their neurological functions, prebiotics may also affect mood, memory, learning and some mental disorders by changing the activity and/or composition of the intestinal microflora ^[33]. They can occur as fibre naturally contained in a food product (see point above), but also as a health-promoting food additive. An example of a prebiotic is inulin or fructooligosaccharides. Prebiotics are found in foods such as: in garlic, onion, leek, oat flakes, legumes, asparagus, chicory.

Fourth - fermented products

As a result of the fermentation process or through the interaction of fermented food with microorganisms in our intestines, the diversity of microbiota can increase ^[34]. Some strains of microbes found in food are able to survive digestion, and fermented foods can act as a "vehicle" for the safe transfer of probiotic strains to the intestines ^[35]. For this reason, our diet should not lack such products as: yoghurt, kefir, pickled cucumbers, sauerkraut, pickled beets, kimchi, kombucha.

Fifth - antioxidants

Long-term exposure to excess free radicals present in the body, from polluted environments or smoking can cause disturbances in the environment and microorganisms that can lead to many intestinal diseases, such as dysbiosis, SIBO, IMO, intestinal damage and infection, colorectal cancer or inflammatory bowel disease. Recently, it has been shown that food-derived antioxidant compounds can protect the human body from oxidative stress by modulating the composition of beneficial microbial species in the gut. Antioxidants are also being researched in mental disorders. It turns out that the antioxidant capacity is lower and the oxidative damage is greater in the brains of patients with depression compared to healthy people ^[36]. Noteworthy are antioxidant vitamins, polyphenols, carotenoids and bioactive peptides from food ^[37]. Products rich in these compounds include: olive oil, coffee, blueberries, raspberries, blackberries, currants, blueberries, pomegranates, green tea, cocoa, grapes, nuts, seeds, asparagus, onions. It is also impossible not to mention spices with high antioxidant potential, such as: turmeric, cinnamon, ginger, rosemary, cloves, oregano, cumin, basil, thyme. Speaking of vitamins with antioxidant functions, we must pay attention to vitamin C, vitamin E, beta-carotene.

Sixth - anti-inflammatory products

Although anti-inflammatory products usually also have antioxidant effects, it is worth mentioning additional compounds that deserve special attention in the context of intestinal health. It has been noticed that omega-3 fatty acids affect the composition of the intestinal microflora. Moreover, the beneficial role of omega-3 supplementation in behavioural disorders may consist in regulating the composition of the intestinal microbiota ^[38]. In addition, omega-3 fatty acids, belonging to polyunsaturated fatty acids, reduce the concentration of pro-inflammatory cytokines, the presence of which is indicated in mental disorders, through their anti-inflammatory effect ^[39]. These acids can be found mainly in fatty sea fish, fish oil and some types of algae. For many people, due to dietary preferences, supplementation will be the best solution.

Seventh - a healthy body weight

Abnormal body weight, including overweight and obesity, may correlate with a reduced diversity of gut bacteria. In the case of reducing the body weight of overweight and obese patients to the correct body weight, the microbiota composition is improved ^[40]. This means that maintaining a healthy body weight is one of the elements of taking care of our intestines. Although the relationship between the gut and obesity is not fully understood, understanding the role of the gut microbiome in managing body weight and health may lead to revolutionary changes in the treatment of this disease in the future. At the moment, we know that the gut microbiome has an impact on nutrient metabolism and energy expenditure. In addition, various treatments for obesity have been shown to alter the diversity and composition of the gut microbiota ^[41].

Eighth - regular, moderate physical activity

Regular and moderate physical activity has a positive effect on gut health by reducing inflammation and intestinal permeability, as well as improving body composition, which in itself can positively affect the composition of the intestinal microbiota. On the other hand, intense exercise can increase the permeability of the intestinal epithelium and reduce the thickness of the intestinal mucus, potentially allowing pathogens to enter the bloodstream. This, in turn, may contribute to an increase in the level of inflammation and thus interference with the functioning of the brain-gut axis ^[42]. Therefore, it will be beneficial for every citizen to implement the universal recommendations of 150-300 minutes of low or medium physical effort per week, which will have a positive effect on our microbiota. Although it can be a huge challenge for a person with mood disorders or depression to engage in exercise, the latest reports are increasingly emphasising that it is worth trying. In clinical trials, the inclusion of exercise with simultaneous psychotherapy and pharmacotherapy may lead to a reduction in the symptoms of depression and anxiety ^[43].

Ninth - Sleep

Sleep plays an important role in the regulation of metabolic, immune and neurobehavioral functions. It turns out that proper intestinal microbiota is essential for proper sleep physiology. On the other hand, abnormal sleep patterns and duration have been shown to affect the composition, diversity and function of the microbiota by affecting the brain-gut-microbiota axis. There are also interventions aimed at improving the microbiota that lead to improved sleep quality ^[44]. Therefore, it seems reasonable to take care of good quality sleep, as well as sleep hygiene, i.e. darkened bedrooms, optimal temperature for falling asleep and calming down before bedtime. Although insomnia, excessive sleepiness or sleep disorders are sometimes found in mood disorders or depression, it is worth knowing that this is an important factor for intestinal health ^[45].

Depression is a treatable disease

The relationship between mental disorders and diet and gut health is still being explored. At the same time, it is worth emphasising that depression is a serious illness. According to WHO data from 2021, over 280 million people worldwide suffer from depression ^[46]. The most important methods of treating depression include pharmacotherapy and psychotherapy. If you feel that you need help - contact your doctor immediately. No diet or supplement can replace the above treatment methods. At the same time, when considering the inclusion of any dietary supplement, consult your doctor or pharmacist due to possible interactions and side effects with the simultaneous use of antidepressants / anxiolytics. However, it is worth thinking about modifying your diet to support your mood and well-being with products supporting the intestinal microbiota.

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