In a recent study published in the journal Biological Psychiatry, scientists have shed light on the pivotal role played by the gut microbiome in the development of mental disorders, including major depressive disorder and bipolar disorder.
Introduction
The groundbreaking discovery of the gut microbiome-brain axis has revolutionized the field of psychiatry. Extensive case-control studies have delved into the intricate relationship between gut bacterial communities and human mental health.
Evidence strongly suggests that the gut microbiome wields significant influence over mental health conditions by modulating a myriad of biological processes. These encompass the immune system and inflammation, mitochondrial dysfunction, oxidative stress, tryptophan-kynurenine metabolism, neuroendocrine metabolism, blood-brain barrier integrity, and neurotransmitter production.
In this study, researchers explore the role of less-explored gut microorganisms, including viruses, fungi, archaea, and parasites, in shaping the pathophysiology of mood disorders.
The Gut Virome
The gut virome comprises both prokaryotic and eukaryotic viruses, alongside plant viruses from dietary sources. The gastrointestinal (GI) tract hosts the highest abundance of viruses, with bacteriophages, which infect bacteria, constituting approximately 95% of the gut virome.
Viruses, particularly bacteriophages, play a pivotal role in influencing mood disorder pathophysiology by modulating immune system functions and altering gut bacterial populations. In animal models of stress-induced depression, changes in the composition of the gut virome have been observed, correlated with shifts in fecal levels of neurotransmitters and metabolites.
In non-human primate models of depression, correlations have been established between altered gut virome composition, changes in brain and peripheral lipid metabolism, and mood disorders. Furthermore, variations in gut virome abundance have been documented in individuals with major depressive disorder.
The Gut Mycobiome
The gut mycobiome, constituting approximately 0.1% of the gut microbiome, comprises the fungal population, significantly influenced by dietary choices.
Studies have illuminated the impact of the gut mycobiome on mood disorder pathophysiology through its effects on human immune system functions and the composition of gut bacteria. Notably, increased levels of antibodies against specific fungi, such as Saccharomyces cerevisiae and Candida albicans, have been observed in individuals with schizophrenia and bipolar disorder. Major depressive disorder has also been associated with alterations in gut mycobiome composition, alpha diversity, and disrupted interactions between gut bacteria and fungi.
The Gut Archaeome
Archaea, prokaryotic microorganisms primarily associated with methane production, hold relevance in mood disorder pathophysiology. Methanogens, the dominant archaea in the gut, utilize hydrogen derived from bacterial fermentation to produce methane.
Studies have reported an enrichment of methanogens in certain mood disorders. These archaea influence mood disorder pathophysiology by modulating the metabolism of bile salts, trimethylamine, and trimethylamine-N-oxide.
The Gut Parasitome
Protozoa and eukaryotic parasites, including helminths, which are commensal parasites residing in the gut, have beneficial effects on human health. Parasites are known to influence the composition and diversity of the gut bacterial population.
Parasitic infections have been linked to a higher prevalence of mental disorders and an increased risk of psychiatric conditions. Helminth therapy, with promising outcomes in immunological diseases, is being explored as a potential treatment for mental disorders.
Oral Microbiome and Mental Disorders
The oral microbiome, primarily composed of bacteria, exhibits less diversity compared to the gut microbiome. Dietary choices, especially the consumption of highly fermentable carbohydrates, can impact the composition of the oral microbiome.
Research has identified associations between the abundance of specific bacterial taxa in saliva and the presence of depression and anxiety symptoms in young individuals. Additionally, alterations in bacterial taxa in subgingival samples have been noted in patients with bipolar disorder.
The oral microbiome can influence mental health through various mechanisms, including direct translocation of microorganisms from the oral cavity to the brain via facial nerves and the olfactory bulb, as well as disruption of the oral-gut microbiome axis leading to neuroinflammation.
Small Intestinal Microbiome and Mental Disorders
The small intestine plays a crucial role in food digestion and nutrient absorption, emphasizing the significance of the small intestinal microbiome in human health. Preclinical evidence indicates associations between the small intestinal microbiome, nutrient and bile acid metabolism, and mucosal immunity.
Given the established connection between healthy dietary patterns and reduced risk of depressive and bipolar disorders, researchers are now investigating the influence of the small intestinal microbiome on mood disorder pathophysiology.
The Aerobiome and Mental Disorders
The aerobiome refers to environmental microorganisms present in inhaled air, potentially influencing the lung microbiome and, by extension, the brain. The emerging field of the lung-brain axis has identified the potential role of the aerobiome in mood disorder pathophysiology.
Exposure to air pollution has been linked to an increased risk of anxiety and depressive symptoms. However, the precise extent to which the aerobiome mediates these effects remains a subject of ongoing research.
Therapeutic Management of Mental Disorders
Fecal microbiome transplantation from healthy donors has demonstrated the ability to alleviate depressive symptoms in patients with irritable bowel syndrome (IBS). Large-scale randomized controlled trials have affirmed the safety and efficacy of fecal microbiome transplantation in improving gastrointestinal symptoms and overall quality of life in individuals with moderate-to-severe major depressive disorder. Encouraging results have also emerged for bipolar disorder patients.
Postbiotics, preparations containing non-viable microbes and their cellular components, have shown promise in reducing symptoms of depression and anxiety in animal models. Additionally, bioactive metabolites produced during bacterial fermentation processes exhibit neuroprotective properties and are currently undergoing clinical investigation as potential treatments for mental disorders.
Dietary interventions, when employed as adjunctive treatments, have exhibited promise in managing major depressive disorder. They operate through a multifaceted approach, impacting the immune system, brain plasticity, neurotransmitters, stress response systems, gene expression, mitochondrial function, and gut microbiota.
The analysis of the gut microbiome’s composition for identifying at-risk individuals and tailoring personalized treatments is gaining prominence in the field of psychiatry. Furthermore, the composition of the gut microbiome has been found to influence therapeutic responses in patients with major depressive disorder and bipolar disorder, potentially due to its effects on drug bioavailability and metabolism.
