When we talk about “microbes or microorganisms,” we immediately think of infection, contamination, or disease, as that is how they have been perceived for many years. However, science currently shows us a different reality.

Our body is a symbiosis of bacteria, fungi, viruses, and archaea that form the microbiota and constitute the microbiome of the entire organism, though the most studied site has been the gut microbiota.

Although most research has focused on gut bacteria, recent findings highlight that gut fungi are also important in the maturation and proper functioning of the gut-brain axis and can have a far-reaching effect on the gut at a systemic level.

Gut fungi are emerging as a potential target in the prevention and treatment of digestive and even neurological diseases, participating in keeping the microbiome-gut-brain axis in good shape. Among the most studied ways in which the gut microbiome communicates with the brain are neurotransmitters, the gut immune system, and metabolites derived from microorganisms (short-chain fatty acids, such as butyric, propionic, and acetic acids).

SCFAs (short-chain fatty acids) are saturated aliphatic organic acids consisting of one to six carbons; acetate, propionate, and butyrate are the most abundant and are present in the colon and feces. SCFAs are produced by gut bacteria through the saccharolytic fermentation of carbohydrates that escape digestion and absorption in the small intestine.

The amount and type of fiber consumed have significant effects on the composition of the gut microbiota and, therefore, on the type and amount of SCFAs produced.

SCFAs could directly influence neuronal function by reinforcing the integrity of the blood-brain barrier, modulating neurotransmission, influencing neurotrophic factor levels, and promoting memory consolidation. There is growing evidence suggesting a potential key role for SCFAs in signaling along the gut-brain axis.

The microorganisms of the microbiota constitute an organ and perform functions that allow for good metabolism and contribute to health.

In the gut, they help digest fiber, produce essential nutrients (such as short-chain fatty acids, vitamin K, and most B vitamins), train our immune system, and protect us from harmful pathogens—provided that each microorganism is in the right place and in balance.

It is important to consider that every person has their own unique microbiota and that they may react differently to different foods and supplements.

One of the most researched areas is the connection between the gut and the brain.

Gut microbes are constantly communicating with the brain, which influences stress and emotions. The vagus nerve, hormones, immune cells, and metabolites are also involved in the gut-brain connection: they all form a team that makes bidirectional communication between the gut and the brain possible.

In recent years, many studies have been conducted that verify the enormous importance of the trillions of microbes in our microbiota, especially those residing in our gastrointestinal tract, in all aspects of our lives (Yong, 2016).

The fundamental role of the microbiome (the genetic material that encodes our microbiota) in regulating immunity has been known for decades, but the relationship of the microbiota with other body systems is relatively new.

Studies by Bailey et al. in 1999 and Savage in 1974 on mice, and the publication by Sudo et al. in 2004, already confirmed that when there was a deficiency of microbiota (germ-free), brain alterations and an altered response to stress were detected. These studies encouraged several research groups to study the importance of the relationship between the microbiome and microbiota with the immune system and the brain (Gaykenma et al., 2004; Goehler et al. 2008; Lyte et al. 2006), leading to the conclusion that evidence indicates that the immune system is key in its relationship with the microbiome, the brain, and behavior (Bailey, 2010; Cryan, 2017).

In the last decade, advanced studies in humans have validated this relationship (Collins and Bercik, 2013; Mayer et al, 2014; Pinto-Sánchez et al., 2017; Tillisch et al., 2013).

In the field of psychoneuroimmunology, the effects of stress and emotional disorders on the immune system have been evidenced, as well as the identification of two stages of the life cycle (childhood and old age) as key in the influence of brain/gut interactions (Gur et al. 2017).

These findings suggest that the microbiome may play a role in the development of dementia, autism, and other disorders. However, we still do not know if the alteration of the microbiome is the cause of brain diseases or merely a consequence.

Diet is one of the most important factors in regulating the composition of the microbiome (Cani and Everard, 2016; Sandhu et al., 2017). Therefore, this has been a relationship of great interest to researchers. Davis et al. demonstrated in 2017 that omega-3 fatty acid (DHA) could reduce anxious behavior in male mice.

Many subsequent studies have highlighted the role of diet in the microbiome and brain function, and studies have been developed on the use of prebiotics and probiotics to modulate gut microbiota functions.

Prebiotics have been extensively researched, and it has been shown that they could influence cognitive outcomes by modulating the microbiota/gut/brain axis.

According to the ISAPP (International Scientific Association for Probiotics and Prebiotics, 2017), a prebiotic is a substrate that is selectively utilized by host microorganisms that confers a health benefit. This category includes, for example, fructooligosaccharides (FOS), inulin, and galactooligosaccharides (GOS).

A new randomized controlled trial found that a prebiotic mixture with inulin and fructooligosaccharides (FOS) taken for 12 weeks can improve cognition and is well-tolerated in healthy volunteers over 60, along with a protein intervention and resistance exercises. Overall, the new study provides evidence on the beneficial effects of prebiotics on the microbiota-brain system in older adults to improve cognition.

In this regard, it seems reasonable to promote a diet based mainly on unprocessed plant foods, with some fermented foods, for the maintenance of mental health in older adults.

Currently, communication between gastrointestinal tract microorganisms and the brain via the gut-brain axis has gained importance as a potentially viable target for modulating brain health. The composition and function of the gut microbiota are strongly influenced by dietary factors that alter gut-brain signaling.

It was demonstrated in animals that there is an impact of prebiotics and probiotics on brain, behavioral, and immune pathologies. This has led to the emergence of the concept of psychobiotics (Sarkar et al., 2016). In humans, some studies suggest that prebiotics and probiotics are capable of affecting behavior (Allen et al., 2016; Schmidt et al., 2015; Steenbergen et al., 2015; Tillisch et al., 2013).

Psychobiotics are defined as probiotics that, when ingested in a specific quantity, provide benefits to the host's mental health through interaction with commensal gut bacteria. It has been found that these bacteria provide their benefits mainly through the hypothalamic-pituitary-adrenal (HPA) axis, immune response and inflammation, and the production of neurohormones and neurotransmitters.

The consumption of psychobiotics could be considered a viable option for caring for and restoring mental health, without unwanted side effects, and presenting a lower risk of allergies and less dependence compared to psychotropic drugs.

Furthermore, the oropharyngeal and gut microbiota have been increasingly linked to schizophrenia (Dickerson et al., 2017). Bipolar disorder has also been associated with significant changes in the microbiota.

The relationship between gut microorganisms and mental health has been studied for many years and has a long history. Although scientists still do not know the exact mechanisms involved in how they shape mental health disorders such as anxiety or depression, emerging studies suggest that following a balanced diet could improve our mood.

This means that by choosing a diet rich in fruits, vegetables, and fish, our chances of avoiding mental health disorders such as depression increase. The benefits of omega-3 fatty acids, especially DHA, of prebiotics and probiotics, and of dietary fibers such as inulin and beta-glucans have also been studied.

It has been shown that specific probiotic bacteria influence brain functions, which leads us to the concept of psychobiotics, which include probiotics and prebiotics, along with other means to act on the microbiome for the benefit of mental health. Although it is not yet possible to apply the promising recent advances in the use of the gut microbiome to address psychiatric disorders to daily life, a better understanding of the importance of the gut as a driver of mental health and treatments focused on the gut microbiome could help improve brain and mental health and predict which patients respond best to medical and nutritional interventions.

Some advances in the gut mycobiota (fungi) are anticipated, which are still early but could be relevant in the future.

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