The last twenty years have seen a growing body of scientific research suggesting what many ancient cultures have long believed: that the brain and the gut are closely connected and influence each other. (1)
This fascinating relationship is bidirectional, meaning that the brain impacts the gut, and the gut, in turn, influences the brain.
This new scientific understanding is contributing to the field of integrative medicine and opening the door to potential novel approaches that focus on the gut to support mental health, including conditions like depression. Many psychiatrists are recognizing that gut health and mental health are interconnected.
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The Gut Microbiota Explained
Our human gut is home to trillions of microbes, 95% of which are friendly and beneficial to our existence. (2) Collectively, these microbes are known as the gut microbiota. The total genetic material contained in the gut microbiota is called the gut microbiome. The communication pathway between the gut microbiota and the central nervous system (CNS) is largely mediated by the vagus nerve and is referred to as the microbiota-gut-brain axis.
Our gut microbiota consists of a delicate balance of bacteria, archaea, fungi, protozoans, and viruses that perform many essential bodily functions, including producing vitamins, synthesizing brain neurotransmitters, digesting food, improving gut motility, and providing vital immune system support.
When pathogens disrupt the delicate balance of the gut microbiota (a condition known as gut dysbiosis), the optimal functioning of the gut may be affected, and various health effects can occur, including potential impacts on mental health.
The Gut Microbiota in Depressed Patients
Research has indicated that the gut microbiota in individuals with depression may differ from that of individuals without depression. Namely, those with depression tend to have a less diverse ecosystem of bacteria in their gut as well as more harmful bacteria compared to beneficial bacteria. (3)
A 2023 systematic review and meta-analysis published in the journal Translational Psychiatry found that individuals with depression had higher numbers of pro-inflammatory bacteria and fewer numbers of anti-inflammatory bacteria. (4)
A 2022 study of over 2500 human subjects found that certain bacteria, namely Sellimonas, Eggerthella, Lachnoclostridium, and Hungatella, were more prevalent in people with depression. (5)
Another systematic review published in 2022 in the journal Molecular Psychiatry also concluded that the gut microbiota composition in individuals with depression was different compared to healthy controls. In this review, study subjects with either major depressive disorder, bipolar disorder, or schizophrenia were found to have lower levels of bacteria that produced helpful short-chain fatty acids (butyrate), higher levels of bacteria that produced lactic acid, and higher levels of bacteria involved with glutamate and GABA metabolism. (6)
Enter Probiotics, Prebiotics, and Psychobiotics
Probiotics (good bacteria) are beneficial collections of live microorganisms that may support health when consumed in sufficient quantities. (7)
Prebiotics are fibrous foodstuffs that humans are unable to digest but that probiotic bacteria thrive on. Examples of prebiotics include bananas, apples, onions, and garlic.
Psychobiotics, a term coined in 2013 by researchers, refers to probiotics and prebiotics that may have positive mental health effects and could support mental well-being. (8)
Probiotics and Depression: Evidence-Based Research from 2021 to the Present
Over the last decade, numerous studies have provided evidence suggesting the role of probiotics in supporting mental health. Here we discuss three recent studies from 2021 onwards:
A 2021 pilot study in humans with major depressive disorder found that a combination of the probiotics Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 was associated with improved mood and anxiety in 4 weeks. Study subjects completed the Montgomery-Asberg Depression Rating Scale (MADRS) before and after the study, and answers indicated that depressive symptoms had improved from a “moderate” to a “mild” rating. (9)
A 2022 double-blind, randomized controlled trial evaluated the efficacy of Bifidobacterium breve CCFM1025 in 45 human subjects with depression. Results showed a significant decrease in depression in one month, as measured by the Hamilton Depression Rating Scale-24 (HDRS-24). (10)
Another double-blind, placebo-controlled, randomized clinical trial published in JAMA Psychiatry in 2023 found that subjects given probiotics experienced fewer depressive symptoms compared to controls. (11)
Participants in this study were given 8 billion colony-forming units (CFUs) per day of a multistrain probiotic for 8 weeks in addition to their ongoing antidepressant medication. Results suggested that probiotics may help support mood and were well tolerated with no serious adverse side effects – an important consideration when deciding whether to add probiotics to the standard of care for depression.
But How Exactly Might Probiotics Support Mental Health?
Research suggests that probiotics may exert their effects on mental health by influencing numerous interrelated body systems:
Proposed Mechanisms of Action
1. Anti-Inflammatory Effects: Both systemic inflammation as well as neuroinflammation have been linked to depression. Probiotics may help manage inflammation by modulating the immune response and reducing levels of pro-inflammatory cytokines, such as TNF-alpha, IL-1, and IL-6. (12)
2. Increasing Neurotransmitter Levels: Probiotics may increase the production of neurotransmitters such as serotonin, gamma-aminobutyric acid (GABA), and dopamine. (13) These neurotransmitters play a critical role in mental health. Certain strains of probiotics, including Lactobacillus and Bifidobacterium, have been shown to produce these neurotransmitters, which may help explain how probiotics could support mood.
3. Strengthening the gut barrier: A "leaky gut" can lead to systemic inflammation as well as neuroinflammation, potentially contributing to mood changes. Probiotics may help support gut health by fortifying the intestinal mucosal barrier and reducing intestinal permeability, thereby helping to keep harmful pathogens out of the bloodstream. (14)
4. Regulation of the Stress Response: The hypothalamic-pituitary-adrenal (HPA) axis plays a crucial role in the body's response to stress. Dysregulation of the HPA axis is commonly observed in individuals with depression. Probiotics, specifically Lactobacillus and Bifidobacterium species, have been shown to influence HPA axis activity by potentially reducing cortisol levels. (15)
5. Enhancing Neurogenesis and Neuroplasticity: Emerging research in animal models suggests that multi-strain probiotics may contribute to the formation of new neurons in the hippocampus and improve neuroplasticity in the brain, thus potentially supporting mental health. (16)
Considering Probiotics for Mental Health: The Latest Clinical Guidelines
In 2022, The World Journal of Biological Psychiatry published global clinical guidelines for supporting mental health using nutraceuticals and phytoceuticals.
The guidelines included a “provisional recommendation” for the use of probiotics as adjunctive support in mental health care. The authors defined a “provisional recommendation” as “a level of evidence with mainly positive data from either meta-analyses or meta-reviews or two randomized-controlled trials of good or average quality, with robust, acceptable, or fair safety/tolerability.” (17)
Specifically, the clinical statement regarding probiotics stated:
Probiotic strains (e.g., Lactobacillus and Bifidobacterium spp.) at doses of 1–10 billion units per day are Provisionally Recommended for Adjunctive use and Weakly Recommended for Monotherapy use in MDD (Major Depressive Disorder)
The guidelines go on to mention that the most studied probiotics in the context of mental health are:
- Lactobacillus and
- Bifidobacterium
However, the authors also mention that there is still no consensus on exactly which specific strains are most beneficial in supporting mental health.
Implementing Probiotics in Clinical Practice: Key Points to Consider
As we synthesize the research and decide on the best path forward for our patients, here are some key points to keep in mind:
- An abundance of research suggests that probiotics may have a beneficial impact on mental health. A 2023 umbrella meta-analysis—umbrella meta-analyses are widely considered the best scientific evidence available—concluded that probiotics were associated with reduced depressive symptoms in humans and suggested that administering a dosage of > 10 × 109 CFU for more than 8 weeks may confer the highest chance of positive results. (18)
- Probiotics are generally considered safe with minimal side effects
- Given current evidence, probiotic supplements can be considered as adjunctive support when addressing mental health in adults. This means that they can be used in addition to standard medications, not in place of them.
- Multi-strain mixtures containing Lactobacillus and Bifidobacterium spp. have evidence suggesting their potential to support mental health. Clinical evidence suggests that using probiotic supplements for at least 8-10 weeks, at doses of at least 10 billion colony-forming units per day, may increase the likelihood of experiencing positive mental health benefits.
- While probiotics are generally well-tolerated, clinicians should exercise caution when recommending probiotics to vulnerable populations, such as the elderly, the immunocompromised, pregnant women, and children.
- In addition to probiotic supplements, clinicians can encourage patients to consume probiotic-rich foods, such as cultured buttermilk, cottage cheese, apple cider vinegar, and olives.
- Psychoeducation on the gut-brain connection can help patients understand the reasoning behind our suggestions and can go a long way to improving adherence.
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Key Takeaways
In summary, as we continue to uncover the intricacies of the gut-brain connection, considering probiotics as part of a comprehensive approach to mental health care represents a holistic, evidence-informed strategy. As psychiatrists and mental health professionals, we’re uniquely positioned to help our patients understand the important connection between mental health and gut health. By embracing a more integrative, mind-body approach to mental health care, we offer our patients the best likelihood of supporting their well-being - both mentally and physically.
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