Introduction
As trillions of viruses, bacteria, fungi, and archaea reside in various parts of the human body, but the most densely populated area is the gastrointestinal tract, the gut microbiota has appeared as a central conduit in the regulation of important body processes, including brain and behavior. In the human gut, more than 1000 species have been identified which are associated with different functions and positive or negative effects for the host. Significantly, evidence is accumulating on the effect of microbiota on mood and behavior. However, the involvement of the gut microbiota in mental disease processes and the potential to alter the microbiota through external facets makes microbiota-targeted interventions a promising avenue for the development of new therapeutic methods. The exogenous factors whose benefit to mental health is partly mediated by gut microbiota are referred to as psychobiotics. Although the term originally referred to probiotics, additional methods can now be regarded as potential psychobiotic, including Synbiotics, probiotics, fecal microbiota transplants, postbiotics, and dietary agents. This review summarizes the state of the literature and the latest advances in the development of microbiota-targeted interventions for the management of psychiatric diseases and mental health and discusses the gaps in knowledge that need to be filled to include gut-targeted therapies in patient care.
Figure 1.Proposed microbiota-targeted interventions for mental health. Various microbiota-targeted interventions have been examined as potential approaches for mental health, including mood and anxiety disorders. These include psychobiotic supplements like prebiotics or synbiotics, probiotics, as well as dietary approaches or fecal microbiota transplants.. Adapted from source.
Probiotics
Probiotics are determined as live microorganisms that, when administered in sufficient amounts, confer a health benefit on the host. The potential psychobiotic effect of probiotics has been broadly studied, with the most studied strains being bifidobacteria or lactobacilli. Additionally, microbial consortia (multiple strains of probiotics) have been used to enhance the efficacy or induce additive or synergistic effects. In healthy populations, a decrease in anxiety, stress, and depression after probiotic supplementation is repeatedly indicated.
In patient populations, recently improved clinical symptoms of depression were observed in an open-label pilot study using the combination of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 and in a population with Generalized Anxiety Disorder, a decrease in anxiety symptoms was elicited through a multistrain probiotic containing Bifidobacterium longum, Bifidobacterium bifidum, Bifidobacterium lactis, and Lactobacillus acidophilus. It is crucial to note that studies using single as well as multiple strains of probiotics do not always lead to the desired outcome. Due to limited evidence available to date, the use of probiotics for mood disorders as a stand-alone therapy remains unsupported, and some of the positive findings observed in preclinical models are yet to be summarized into clinical practice.
Prebiotics
Prebiotics are determined as substrates that are selectively utilized by the host microorganisms conferring a healthy benefit on the host. In light of potential technique and pragmatic complications associated with probiotic approaches, like ensuring the survival of the probiotic transiting through changing pH levels of the digestive tract, the probiotic’s inability to colonize the colon in the long term, and the selection of appropriate strains. Overall prebiotic approaches to mental health remain less studied when compared to probiotic interventions and limited data from human cohorts demonstrate the need for more well-defined clinical cohort studies. For example, in a cohort of healthy females a decrease in preclinical anxiety after a galactooligosaccharide intervention was observed, whereas no impact on depressive symptoms was seen in a population with Major depressive disorder using the same prebiotic.
It should also be mentioned that besides fermentable carbohydrates, other nutrients have been indicated to retain prebiotic properties, like polyphenols or omega-3 fatty acids, with benefits to mental health and well-being. Polyphenol consumption has been linked to many health benefits like a decrease in depressive symptoms, whereas eliciting concordant changes in the gut microbiota. Therefore, while much more research into the therapeutic effect is needed, these compounds might become available as microbiota-targeted interventions for mental health.
Synbiotics
Synbiotics (a mixture comprising live microorganisms and substrate selectively utilized by host microorganisms that confers a health benefit on the host) are arising as another approach to modulate the gut microbiota and influence mood and behavior. Although the concept of Synbiotics was first described 25 years ago, research on managing symptoms of psychiatric diseases is still few. However, positive outcomes were reported in recent studies using synbiotic supplementation, demonstrating improvements in stress, depression, and anxiety levels in specific populations like patients undergoing haemodialysis or with coronary artery disease.
Postbiotics and Microbial Metabolites
Postbiotics and microbial metabolites are another potential gut-targeted intervention. Recently, postbiotics were determined as preparations of inanimate microorganisms or their components that confer a health benefit on the host. Thus postbiotics are deliberately inactivated microbial cells which must be present with or without metabolites to be effective. The health benefits could be mediated through alterations in the microbiota, improving the intestinal barrier function, and modulation of immune or metabolic responses. Due to the potential benefits regarding formulation, safety, and regulation, the therapeutic use of postbiotics could become more available and open up new horizons in the treatment of psychiatric disorders.
Faecal Microbial Transplant
The potential of a long-lasting reconstruction of the existing ecosystem makes faecal microbial transplant (FMT) an appealing treatment method for patients with psychiatric disorders and associated microbial imbalances. Data from animal models establish a promising basis for clinical trials as it indicates that faecal microbial transplant can be effective in reversing adverse behaviours and neuroinflammation and improving anxiety and depression-like behaviour. However, most human studies to date have been small or case-control, only one larger human trial including 83 patients with inflammatory bowel disease and self-reported depression documented substantial improvements in fatigue after faecal microbial transplant.
Whole Dietary Interventions
The significance of diet in supporting mental health and cognitive function is increasingly identified. Comprehensive observational data from large cohort studies from different countries and cultures have linked dietary patterns and diet quality (including high fibre and fruit intake) to better mental health outcomes. In animal models, microbiota-dependent benefits of intermittent fasting and the ketogenic diet have been documented. In human cohorts, an 8-week nutrition education program focusing on microbiota-friendly foods decreased depression scores and increased self-rated health and subjected well-being score in an obese population in Japan.
Fermented Foods
Significantly, it has been presented that the health benefits of fermented foods (foods made through desired microbial growth and enzymatic conversions of food components) could be associated with the presence of live microorganisms, prebiotics, and potential microbial metabolites produced through the fermentation process.
| Key Points 1- The microbiota has occurred as a key player in impacting brain processes, mood, and behavior. 2- Modifying the gut microbiota as a treatment method for developing new alternative therapies for patients resistant to existing pharmacological methods. 3- Promising evidence is presented for using gut-targeted interventions like probiotics, prebiotics, or diet as adjuvant therapies in mood and anxiety disorders. 4- Gut-targeted approaches are likely to become a significant component in the management of psychiatric and psychological disorders. 5- However, research gaps need to be addressed to incorporate these approaches as standard treatments in patient care. |
Conclusion
A plethora of review articles are available outlining the potential of using psychobiotics in the management of psychiatric disorders, however many advances have been made towards the use of microbiota-targeted interventions as adjuvant therapies for some diseases like depression. Probiotics often do not colonize the gut and do not become members of the gut community, which makes it necessary to ingest probiotics. Prebiotics or diet, on the other hand, has the option to alter the microbiota. Therefore, most gut-targeted approaches may be life-long interventions.