Mood and the microbiome

Mental health conditions are rising worldwide, with a 13% increase in mood disorders and substance use in the last decade.¹ The most common mental health conditions, depression and anxiety, costs the global economy an estimated $1 trillion each year.¹ While we have many effective nutritional and herbal therapeutics to help manage stress and mood disorders, as with most things, gut health also plays a significant role. Research into the gut-brain-microbiota (GBM) axis has shone a light on the connection with mood disorders. As such, ‘psychobiotics’ are gaining popularity as a novel class of probiotics that bring about mental health benefits.²

The gut-brain-microbiota axis is a two-way street

There is increasing evidence to support the importance of gut health on brain function. Through a bidirectional communication network, signals from the brain can influence the motor, sensory and secretory processes of the gut and in turn, these visceral messages from the gut can influence brain function.³ There are several mechanisms by which this communication occurs, including vagal, immune, neuroendocrine, and neurotransmitter pathways (Figure 1).²

The gut microbiota communicates with the vagus nerve via several mechanisms. Firstly, the diffusion of bacterial compounds or metabolites from microbiota in the intestinal lumen can be sensed via afferent vagal nerve fibres and subsequently relay signals from the gut to the enteric nervous system (ENS) and central nervous system (CNS).⁴ Secondly, enteroendocrine cells in the epithelial lining release of neurotransmitters or secrete anorexigenic or orexigenic hormones (such as ghrelin, orexin); directly influencing brain function and behaviour.^4,5

Another way in which bidirectional communication occurs is via the hypothalamic-pituitary-adrenal (HPA) axis, the immune system and cytokine communication. The HPA axis regulates the stress response and glucocorticoid (cortisol) secretion, which can affect gut barrier permeability and the composition of the microbiome.^2,5 This in turn can dysregulate tryptophan metabolism via the kynurenine pathway, affecting the transmission of serotonin and glutamate.² Conversely, the microbiome modulates the HPA stress response, positively influencing cortisol levels to reduce stress and improve mental processes.^3,6

Research also suggests the brain and the gut microbiota may bidirectionally communicate via the production of short-chain fatty acids (SCFAs).^7,5 These metabolites not only improve microbial diversity and richness but also affect neurogenesis, and maintain blood-brain-barrier (BBB) integrity by increasing the expressions of tight junction proteins in the brain.^5,6 SCFAs demonstrate neuroprotective properties, particularly butyrate, displaying protective effects on psychological and neurodegenerative disorders, including depression.⁶ Some probiotic species, as well as prebiotic fibres and polyphenols, increase the production of SCFAs in the gut, which play important roles in regulatory pathways of the immune system, metabolic health and behaviour patterns.^5,6

Figure 1. The multiple bidirectional routes of communication between the gut-brain-microbiota axis.³

Leaky gut, leaky brain

The impact of stress, particularly in early life stages, is considered one of the most important predictors of the onset of depressive disorders.^6,8 Stress increases pro-inflammatory cytokines, including interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-a) and C-reactive protein.⁹ It also involves both systemic and peripheral release of corticotropin-releasing hormone (CRH), which stimulates cortisol release and can trigger mast cell degranulation, compromising barrier function.¹⁰ As gastrointestinal symptoms are common comorbidities in those with mood disorders,^8,7 maintaining healthy gut integrity may also be considered an important factor in maintaining healthy moods.

Psychobiotics show positive mental health benefits

Studies have demonstrated that some probiotic formulations (mostly including Lactobacillus and Bifidobacterium species) can improve mood in healthy men and women.⁶ Research shows that certain probiotics, including those found in Barrier Probiotic, can trigger IL-10 mediated anti-inflammatory responses by down-regulating the pro-inflammatory cytokines TNF-α and IL-6. These pro-inflammatory cytokines, along with IL-2 and IL-1β, are recognised as key markers in depressive states and other affective disorders.⁸

In a human clinical trial, volunteers participated in a double-blind, placebo-controlled, randomised parallel-group study with probiotics L. helveticus (R0052) and B. longum (R0175) administered for 30 days. The probiotics were shown to alleviate psychological distress, anxiety and depression, demonstrating beneficial psychological effects in healthy human volunteers.¹¹

In a triple-blind, placebo-controlled, randomised study of healthy participants without a current mood disorder, received a 4-week probiotic food supplement intervention with the multi-strain Barrier Probiotic (Bifidobacterium bifidum [W23], Bifidobacterium lactis [W51], Bifidobacterium lactis [W52], Lactobacillus acidophilus [W37], Lactobacillus brevis [W63], Lactobacillus casei [W56], Lactobacillus salivarius [W24], and Lactococcus lactis [W19] and [W58]), while the control participants received an inert placebo for the same period. At the conclusion of the study, it was found that participants receiving the probiotics showed a significant reduction in overall cognitive reactivity to sad mood, which was largely accounted for by a decrease in rumination and aggressive thoughts.¹²

The same multi-strain probiotic has been shown to improve barrier health and integrity in various ways, with results showing measurable reductions of LPS, inhibition of mast cell activation, and stimulation of IL-10.¹³ By improving intestinal barrier health and resolving inflammation, these probiotics play an important role in establishing a healthy communication pathway for the GBM axis.

The microbiome is a new target for mental health

As mental health continues to become an increasing public health issue, new therapeutics to help manage these conditions are welcomed. Psychobiotics are emerging as just that. We know the gut and brain interact bidirectionally, and these particular probiotics have shown benefits not only for gut health but also mood in clinical trials. Modulating the gut-brain interface is a safe and effective consideration for patients with mood disorders, such as depression and anxiety. Combining psychobiotics with herbal and nutritional medicine will also likely have additional benefits. As such, supporting gut health with dietary interventions to improve SCFA production, including prebiotic fibres and probiotics, may indeed become a popular medicine from now and into the future, with Hippocrates adage from 400 B.C. of “all diseases begin in the gut” coming full circle.

References:

1 - World Health Organization. Mental health. [Internet]. [2021. Cited 2021 September 26]. Available from: https://www.who.int/health-topics/mental-health#tab=tab_2

2 - Dinan TG, Cryan JF. The microbiome-gut-brain axis in health and disease. Gastroenterology Clinics. 2017 Mar 1;46(1):77-89.

3 - Dinan TG, Stilling RM, Stanton C, Cryan JF. Collective unconscious: how gut microbes shape human behavior. Journal of psychiatric research. 2015 Apr 1;63:1-9.

4 - Bonaz B, Bazin T, Pellissier S. The vagus nerve at the interface of the microbiota-gut-brain axis. Frontiers in neuroscience. 2018 Feb 7;12:49.

5 - Zou R, Tian P, Xu M, Zhu H, Zhao J, Zhang H, Chen W, Wang G. Psychobiotics as a novel strategy for alleviating anxiety and depression. Journal of Functional Foods. 2021 Nov 1;86:104718

6 - Ganci M, Suleyman E, Butt H, Ball M. The role of the brain–gut–microbiota axis in psychology: The importance of considering gut microbiota in the development, perpetuation, and treatment of psychological disorders. Brain and behavior. 2019 Nov;9(11):e01408.

7 - Cheng LH, Liu YW, Wu CC, Wang S, Tsai YC. Psychobiotics in mental health, neurodegenerative and neurodevelopmental disorders. Journal of food and drug analysis. 2019 Jul 1;27(3):632-48.