Gut-brain connection: How probiotics can improve mental health

In recent years, scientists have increasingly recognized the power of the gut microbiome in influencing physical and mental health. While the central nervous system or the brain regulates emotions, scientists now acknowledge that the gut’s enteric system is crucial in regulating emotions. Scientists discovered the gut-brain connection that the real enteric and nervous systems are interconnected and influence one another. 

The gut-brain connection

Have you ever felt queasy before an interview? Do you feel butterflies when you are excited or about to give a speech in front of a large audience? Do you feel nauseous when confronted with foul smells or just by imagining pending doom?

All these are some outward manifestations of what you are feeling.

The brain sends signals to the enteric system through the gut-brain communication pathway, which might result in stomach upset when you feel overwhelmed or emotional. 

Similarly, the gut can improve mental health by releasing hormones and neurotransmitters important in regulating mood.

For example, gut bacteria produce dopamine, gamma-aminobutyric acid and norepinephrine, which are critical players in triggering feelings of anxiety, reward and happiness [1]. 

What is the gut-brain axis? 

The gut-brain axis is recognized as a bidirectional communication network linking the brain (central nervous system) and the gut (enteric nervous system). 

So, what links these two systems together? The HPA, or the hypothalamic-pituitary-adrenal axis, the autonomic nervous system and the nerves present in the gastrointestinal tract link the brain and the gut.

This link allows the brain to influence activities in the intestine, including the activities of immune effector cells, which are essential in the immune system.

Similarly, the gut affects the brain by regulating cognition, mental health and mood by releasing neurotransmitters and hormones related to mood regulation [2]. 

What about the gut’s microbiota? 

The gut hosts trillions of microorganisms that benefit the body and overall health. These microorganisms, from bacteria to fungi, are called the gut’s microbiota.

Researchers have found that when the population of specific groups of the gut’s microbiota is reduced or altered, this can directly affect the individuals’ mental and physical health and well-being. 

The gut-brain connection: Microbiota

For example, depression, anxiety and autism spectrum disorders are now well-established to have links to disruptions in the gastrointestinal tract.

Meanwhile, gastrointestinal diseases such as irritable bowel disease and irritable bowel syndrome often involve psychological morbidities linked with disruption of the gut microbiome [2]. 

In addition, evidence from literature has shown that the gut bacteria’s composition appears to influence the neurological and brain development of unborn and newborn babies.

It is not surprising that one’s diet affects the gut microbiome, which in turn impacts cognitive function. 

Can probiotics strengthen the gut’s microbiota and improve mental health? 

Probiotics refer to live microorganisms intended to improve individuals’ overall health. These are present in yogurt, dietary supplements and other fermented foods. 

Although many of us may think that microorganisms, such as bacteria, are harmful ‘germs’, many organisms are helpful in the body.

Some of these bacteria aid in the digestion of food, produce vitamins such as vitamins K and B and destroy disease-causing cells. 

Notably, many bacteria in probiotics are the same bacteria that naturally reside in the intestines. Most common probiotics include the following: 

  • Lactobacillus 
  • Bifidobacterium 

Here are some functions of probiotics in the body: 

  • Boost the immune response of the body
  • Produce substances such as neurotransmitters and vitamins that have health benefits for the body
  • Help the gut’s microbiome return to its healthy state after experiencing disruption 

Studies that support the use of probiotics in alleviating depression and anxiety 

Probiotics improve mental functions

A systematic review of studies [3] published in the Current Pharmaceutical Biotechnology revealed that probiotics improve the mental functions of patients with mental health conditions.

The beneficial effects of probiotics were seen in patients with depression, Alzheimer, anxiety and autism spectrum diseases.

Although the study revealed the potential of probiotics in improving mental health, more clinical studies are still needed to confirm the safety and efficacy of these live microorganisms. 

Probiotics in managing depression

A randomized clinical trial [4] published in Translational Psychiatry adds more evidence on the effectiveness of probiotics in managing symptoms of depression.

The study, led by Anna-Chiara Schaub, a professor and researcher at the University of Basel, Department of Psychiatry in Switzerland, investigated whether short-term high-dose probiotics supplementation reduces symptoms of depression through changes in the gut microbiota and neural connections in depressed patients. 

Investigators of the study recruited patients diagnosed with current depressive episodes. Participants were randomized to the probiotic group (n=21) and placebo group (n=26).

The experimental group received a multi-strain probiotics supplement for 31 days in addition to treatment-as-usual, while the placebo group received a placebo and treatment-as-usual.

Methods

The Hamilton Depression Rating Scale (HAM-D) was used at baseline, immediately after the 31-days treatment and at four weeks of follow-up. The HAM-D was used to examine changes in the depression scores of the participants from baseline and at the end of the intervention and during the follow-up period. 

Results of the clinical trial revealed that HAM-D scores significantly reduced over time in the experimental group compared with the placebo group.

Notably, the effects of the probiotic supplementation were sustained over time since, during follow-up, the HAM0D scores were significantly lower in the experimental group compared with their baseline scores.

The changes in HAM-D scores during follow-up occurred in 80% of the patients who received probiotics compared with only 48% in the placebo group. 

Since both groups received treatment as usual, they received the same medications for their depressive episodes; the investigators showed that probiotics had an additional benefit in reducing depression. 

Although the study had a relatively small sample population, the findings were significant. This added to evidence that probiotics supplementation with usual medication or treatment-as-usual would yield higher treatment benefits than treatment-as-usual.

Verifying these findings in more extensive trials in the future would help determine if the same results could still be observed in more extensive population trials. 

Results

Interestingly, the study showed that probiotics improved gut health, which in turn resulted in decreased symptoms of depression. Supplementation maintained the gut’s microbial diversity and improved overall community composition.

In particular, probiotic supplementation increased the Lactobacillus population, which is essential in improving gut health.

In contrast, participants who only received treatment-as-usual and placebo did not show similar results. 

The researchers also performed brain imaging to examine if intake of probiotic supplementation improved grey matter volume. Findings indicated that grey matter volume was significantly enhanced in the probiotics group compared with the placebo group. 

However, the study’s authors cautioned that strict compliance is critical in reaping the benefits of probiotics supplementation.

The researchers pointed out that “notably, in our study, probiotic effects were only significant in a subsample with high compliance and accentuated in the follow-up after eight weeks… the importance of compliance during probiotic supplementation should be highlighted and is as important as in general antidepressant therapy.”

The gut-brain connection: Probiotics supplementation
Photograph: Zinkevych_D/Envato

Probiotics supplementation modulates gut microbiota

Apart from improving the depressive symptoms of the patients, probiotics supplementation also modulated the gut microbiota of the patients.

Notably, the Bacteroides 2 enterotype bacteria’s population, which increases inflammatory cells in the gut and the body, decreased following probiotics supplementation.

In addition, the Prevotella enterotype, regarded as a beneficial microorganism, was maintained in the probiotics group compared with the placebo group. These observations implied that probiotics supplementation would help keep a healthy gut and reduce symptoms of depression. 

The connection between healthy gut microbiota and the reduction of symptoms of depression is based on the ability of the Lactobacillus bacteria in the gut to produce neurotransmitters that improve mood and reduce depression.

Hence, increasing the genus of bacteria in the gut that has neurotransmitters that enhance mood would help reduce symptoms of depression and anxiety. 

Multi-strain probiotics in reducing symptoms of depression

Meanwhile, another randomized clinical trial [5] examined the effects of a multi-strain probiotics formula in reducing symptoms of depression.

The study recruited 40 healthy young adults with a mean age of 20. Participants were randomized to the probiotics group and the placebo group.

Notably, the study was triple-blind, which means that the participants, the investigators and the assessors needed to be informed which group received the probiotics or placebo. Blinding of the groups in the study reduced the risk of bias in the interpretation of the results of the investigation. 

The probiotics formula contained L briefs, L acidophilus, L salivarius, L casei, L lactis, B lactis and B bifidum. The genus Lactobacilli has been associated with overall mental and physical health improvements.

Results of the study revealed that consumption of the probiotics supplementations significantly reduced broad cognitive reactivity to depression. 

Specifically, the study authors found that supplement intake reduced ruminative and aggressive thoughts, which were assessed using the Leiden index of depression sensitivity.

The findings are noteworthy since many young people with no history of depression would prefer non-pharmacologic interventions as their first line of treatment. 

Take home message

Current studies on the effects of probiotics supplementation on mental and physical health showed that it could help maintain a healthy gut, increase the diversity of the microbial population and improve mood or reduce symptoms of depression.

Improving the gut’s health would help the good bacteria produce neurotransmitters that enhance mood and prevent depression. 

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469458/ 
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367209/ 
[3] https://pubmed.ncbi.nlm.nih.gov/31914909/ 
[4] https://www.nature.com/articles/s41398-022-01977-z 
[5] https://pubmed.ncbi.nlm.nih.gov/25862297/ 

Photograph: YuriArcursPeopleimages/Envato
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