Probiotics, Gut Microbiota, and Mental Health

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This entry is adapted from the peer-reviewed paper 10.3390/microorganisms10112141

Probiotics are gradually gaining importance in the field of psychiatry in the form of psychobiotics. The term psychobiotics was introduced to define a new class of probiotics able to produce substances that can affect the gut–brain connection, improve mood, decrease anxiety and depression, and bring many other benefits. The term itself suggests the connection both with the psyche and with the world of probiotics.

mental health probiotics gut microbiota

1. Introduction

Psychobiotics’ studies examine the existing relationship between gut microbiota and mental phenomena; the intake of certain strains of probiotics, such as Bifidobacterium and Lactobacillus, for example, allow the gut microbial system to be modified in order to provide benefits at the psychic, immune, hormonal, and mental levels. Those who suffer from forms of depression, anxiety disorders, chronic stress, low mood, but also people who do not suffer from such disorders, can therefore benefit from the use of psychobiotics. Thanks to probiotics, neurochemicals can in fact be produced within the gut microbiota and interact with receptors of the enteric nervous system that innervate the entire gastrointestinal tract. Once they enter the portal circulation, these substances go on to influence components of the nervous system and ultimately the brain, through what is called the gut–brain axis.

2. Probiotics, Gut Microbiota, and Mental Health

The term probiotic is used to designate microorganisms that can promote human health and well-being. According to the official definition, probiotics are live and viable microorganisms that, when administered frequently and in adequate amounts, benefit the health of the host ^[1]. They share the following requirements and common traits ^[2]:

They are safe for use in humans;
They are active and viable in the gut, and present in sufficient quantity to justify any beneficial effects;
They have an active metabolism in the human intestine, and some strains could persist and multiply;
They confer a demonstrated physiological benefit.

Probiotics must not carry acquired and/or transmissible antibiotic resistance; moreover, it is worth mentioning that their colonization in the intestine is only temporary in nature and ends a few days after discontinuation of their intake.

The clinical effects of probiotics depend on specific bacteria, which should be defined not only by genus and species, but also at the strain level ^[3]. Although there are a few clinical studies that directly compare the effects of various strains within a single species, the available evidence shows that some effects of probiotics are strain-specific, while others may be species-specific. In any case, the clinical effect of a probiotic microorganism should be attributed only to the strains that have been demonstrated to possess it. Conversely, when one strain is not eliciting a certain clinical effect, it does not mean that no other strain can produce it. Therefore, in order to be the subject of a consumer health claim, proper characterization must be carried out ^[3].

The term gut microbiota defines the set of living species that colonize the human gastrointestinal tract, which is considered one of the most densely populated ecosystems in the world with an estimated 100 trillion microorganisms including bacteria, yeasts, protozoa, and viruses. When these communities are in balance with each other, a condition called eubiosis is established ^[4]. This is particularly important because it allows the various components of the gut microbiota to be functionally effective, and above all to be synchronized both with each other and with the other components of the gut ecosystem. Under these conditions, the microbiota can perform several essential functions for the host, including developmental, immunological, nutritional, infection prevention, nutrient acquisition, and brain and nervous system functions ^[4]. Consequently, the role that a well-balanced microbiota plays in eubiosis is critical to the overall health of the body. When this balance is lacking, a condition called dysbiosis is established and can cause various diseases, metabolic disorders, and affect human life.

Gut microbiota changes throughout the course of life, providing each individual with a specific “fingerprint.” Indeed, it develops at birth, diversifies by increasing in composition and becomes stable between the third and seventh decade of life. It is then with aging that its microbial diversity tends to decrease, probably influenced by changes in digestion, nutrient absorption, and weakening of immune activity ^[5].

Studies have shown the presence of 10 predominant microbial phyla in the human gut microbiota. In particular, the phyla Firmicutes, Bacteroidetes, and Proteobacteria represent 90% of the total; the phyla Actinobacteria, Fusobacteria, and Verrucomicrobia account for the remaining 10% ^[5].

In this context, probiotics have a key role, namely to help maintain the health of the microbiota, but also to bring back into balance a microbiota attacked by pathogens or physical stresses ^[6].

Microbiota and the brain are capable of exerting a strong influence on each other through a bidirectional connection, called the gut–brain axis. They communicate through various pathways, including the immune system, tryptophan metabolism, vagus nerve, and enteric nervous system, involving microbial metabolites such as short-chain fatty acids, branched-chain amino acids, and peptidoglycans acting as neurotransmitters ^[7]. This connection not only serves to ensure the proper digestive pathway, but is involved in a multitude of physiological processes including satiety, food intake, regulation of glucose and fat metabolism, hormone secretion and sensitivity (especially to insulin), and bone metabolism. Moreover, thanks to gut microbiota, it is also possible to positively modulate cognitive functions, and it is becoming increasingly evident how important it is in fields studying the biological and physiological basis of psychiatric and neurodegenerative disorders ^[7].

Classic endocrine organs such as the pituitary, thyroid, pancreatic islets, adrenal glands, and gonads produce hormones that are transported by the blood to exert their effects on distant organs through specific receptors. However, it has become apparent not only that these organs produce hormones, but also that all organs communicate with each other through the secretion of specific hormones, exerting effects at a distance depending on the expression of the appropriate receptors ^[8].

The brain, following food intake, receives input from the gut, and determines physiological responses together with signals from other organs ^[8].

Some years ago, the term psychobiotics was introduced to define a new class of probiotics able to produce substances that can affect the gut–brain connection, improve mood, decrease anxiety and depression, and bring many other benefits. The term itself suggests the connection both with the psyche and with the world of probiotics; these microorganisms are in fact able to perform positive functions in the intestine and perpetrate their positive effect on the brain as well, communicating through the bidirectional intestine–brain axis ^[9].

Recent studies, mainly carried out on animal models, support the role of microbes as signaling components in the gut–brain axis, and it has been established that the vagus nerve is the main route for exerting the effects of gut microbiota on the central nervous system.

There are many probiotics that have shown a positive effect in this regard; for example, treatment with Bifidobacterium spp. can increase the amount of tryptophan, precursor of serotonin, the hormone of happiness. Some Lactobacillus and related genera species alter gamma-aminobutyric acid (GABA) metabolism and change brain GABA receptor expression and behavior. Synthesis and release of neurotransmitters from bacteria have been reported: Lactobacillus and Bifidobacterium species can produce GABA; Saccharomyces spp., Escherichia, and Bacillus can produce noradrenaline; Streptococcus, Enterococcus spp., Escherichia, and Candida can produce serotonin; Bacillus can produce dopamine; and Lactobacillus can produce acetylcholine ^[10].

Exploration of the gut microbiota has shown clear benefits on behavior and brain function, and may also aid in the treatment of depression ^[11]. Already in current practice, the treatment of anxiolytic and antidepressive-like behavior has been mediated with Lacticaseibacillus rhamnosus JB-1 oral therapy through the gut–brain axis. Moreover, from numerous studies it was found that a quantifiable set of microbial markers was consistently present in the feces of depressed subjects. These markers can also be used to determine the severity of disease progression.

References

Food and Agriculture Organization of United Nations (FAO); World Health Organization (WHO). Health and Nutritional Properties of Probiotics in Food Including Powder Milk with Live Lactic Acid Bacteria. Report of a Joint FAO/WHO Expert Consultation. Cordoba, Argetina, 1–4 October 2001. Available online: https://www.fao.org/3/a0512e/a0512e.pdf (accessed on 7 October 2022).
Morelli, L.; Salari, P. Handbook dei Probiotici; Mediserve Editoria & Formazione: Milan, Italy, 2007.
Rowland, I.; Capurso, L.; Collins, K.; Cummings, J. Current level of consensus on probiotic science. Gut Microbes 2010, 1, 436–439.
Foster, K.R.; Schluter, J.; Coyte, K.Z.; Rakoff-Nahoum, S. The evolution of the host microbiome as an ecosystem on a leash. Nature 2017, 548, 43–51.
Bibbò, S.; Ianiro, G.; Giorgio, V.; Scaldaferri, F.; Masucci, L. The role of diet on gut microbiota composition. Eur. Rev. Med. Pharmacol. Sci. 2016, 20, 4742–4749.
Available online: https://microbioma.it (accessed on 7 October 2022).
Cryan, J.F.; O’Riordan, K.J.; Cowan, C.S.; Sandhu, K.V.; Bastiaanssen, T.F.; Boehme, M.; Codagone, G.M.; Cussotto, S.; Fulling, C.; Golubeva, A.V.; et al. The microbiota-gut-brain axis. Physiol. Rev. 2019, 99, 1877–2013.
Romijn, J.A.; Corssmit, E.P.; Havekes, L.M.; Pijl, H. Gut–brain axis. Cur. Op. Clin. Nutri. Metab. Care 2008, 11, 518–521.
Anderson, S.C.; Cryan, J.F.; Dinan, T. The Psychobiotic Revolution: Mood, Food, and the New Science of the Gut-Brain Connection; National Geographic Society: Washington, DC, USA, 2017.
Maiuolo, J.; Gliozzi, M.; Musolino, V.; Carresi, C.; Scarano, F.; Nucera, S.; Scicchitano, M.; Oppedisano, F.; Bosco, F.; Ruga, S.; et al. The contribution of gut microbiota–brain axis in the development of brain disorders. Front. Neurosci. 2021, 15, 616883.
Nanthakumaran, S.; Sridharan, S.; Somagutta, M.; Arnold, A.A.; May, V.; Pagad, S.; Malik, B.H. The gut-brain axis and its role in depression. Cureus 2020, 12, e10280.

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1. Introduction

2. Probiotics, Gut Microbiota, and Mental Health

References