"Whether an illness affects your heart, your arm, or your brain, it’s still an illness, and…getting help isn’t a sign of weakness—it’s a sign of strength."

 - Michelle Obama

More than 260 million people worldwide are living with depression, now the number one driver of disability globally [1]. Causes of depression are complex and still unclearly defined, which often makes successful treatment difficult for the relatively few who seek it. It is often accompanied by stress, which ubiquitously wears on mental, emotional, and physical health.

Our Gut Influences Depression

Certain hormones such as dopamine and serotonin influence depression, and our emotions may also be directly affected by chronic inflammation and imbalances in our immune system [2]. Since our gut is the biggest immune system organ within our body and controls the release of 90% of our serotonin, it could be substantial in improving depression.

A Microbiome Boost

Our intestinal microbiota and nervous system interact to regulate neurotransmitters, which affect our stress reactions, anxiety levels, and memory functions [3][4]. Research into the potential of probiotics is inspiring scientists committed to finding novel treatments for depression.

PS128 is leading the psychobiotic field through its ability to regulate dopamine and serotonin in the brain. In preclinical trials, it has also shown evidence for alleviating lack of hope, appetite, and motivation—signs that often accompany anxiety and depression [5].

Study on Mice with Depression-like Symptoms

Research Methods

Researchers stressed laboratory mice to induce depression- and anxiety-like behaviors. This was done with a maternal separation  (MS) model: newborn mice were separated from their mothers for three hours each day from postnatal day two to 14. One group of MS mice and one group of non-MS mice received PS128 daily from postnatal weeks five to eight. Control cohort or MS and non-MS mice received a saline placebo and were compared with the treatment group. The mice were evaluated to determine whether or not the animals taking PS128 exhibited a significan difference in their behavior.

Results

After taking PS128 for four weeks, the MS mice compared to the placebo cohort showed significantly abated signs of emotional distress. Specifically, the PS128 group displayed a stronger will to survive (forced swimming test), a greater desire to explore (open field test), and an increased experience of pleasure (sucrose preference test)—signs that measure depression and anxiety in humans.

 

When separated from their mothers, the test mice were in a stressed state. Compared with mice that remained with their mothers, the stressed group had higher serum corticosterone levels, but after taking PS128, the hormone levels significantly decreased. Chronic stress was relieved, and the psychobiotic appeared to regulate dopamine and serotonin to appropriate, healthy levels, which could stabilize the mice’s emotional states.

01

Happy hormones serotonin and dopamine concentrations were modulated.

The hormone serotonin has a wide range of physiological effects. It influences mood, instilling calm, happy feelings and reducing anxiety. It also plays a part in appetite, sleep, memory, and other functions. The mechanism of many anti-depression and anti-anxiety drugs is serotonin regulation. Dopamine stimulates the brain’s reward system, encouraging active goal achievement and delivering feelings of satisfaction. Deficient levels of dopamine lead to lack of motivation, concentration, and pleasure.

 

At the end of the study, the prefrontal lobes of normal mice and those of MS mice were compared, and the former showed significantly decreased concentrations of serotonin and dopamine. In MS mice that were fed PS128, both hormone levels were notably enhanced, showing the psychobiotic’s potential to reduce physiological markers that contribute to depression and anxiety.

02

Desire to survive and mobility were increased.

During a forced swim test, mice were placed into a standard transparent cylinder half-filled with water for six minutes. Their active swimming and immobile times were recorded and analyzed. MS mice gave up their will to survive much sooner than non-MS mice. When given PS128, the test group’s depression-like symptoms were decreased. They demonstrated a greater desire to survive by swimming more of the time.

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03

Signs of increased confidence and abated anxiety were observed.

Mice are typically risk-averse, remaining next to walls when walking in order to avoid open spaces. This is especially true for mice showing anxious characteristics of anxiety. An open field test allowed lab mice to freely move within an open space, and their traveled path and distance were recorded. Compared with the placebo cohort, MS mice that were given PS128 traveled farther and were emboldened to spend more time in the center area away from the field’s walls. PS128 seemed to lessen their behavioral anxiety.

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04

Motivation and enjoyment were restored.

 

One symptom of stress-induced depression is anhedonia, or the lack of feeling from an activity or reward that normally results in pleasure. While most mice naturally enjoy drinking sucrose water, this preference is reduced in MS mice. After receiving PS128, the stressed mice once again preferred sucrose water, restoring their motivation to seek after a reward.

PS128糖水喜好實驗.png

05

Stress hormone levels were reduced.

 

When lab mice are under pressure, their adrenal glands release a stress hormone (the functional equivalent of cortisol in humans) that helps focus the body’s energy on effectively responding to external stress. Once the stressor is removed, the hormone is restored to baseline and the body returns to a relaxed state. MS mice had stress hormone levels much higher than the non-MS group, but after receiving PS128 for an extended time, the experimental group showed a significant reduction in levels of the hormone, both before and after stress-inducing tests. PS128 was able to regulate and stabilize their stress response.

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[1] GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. (2018). Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. The Lancet.

[2] Kronfol Z. Immune dysregulation in major depression: a critical review of existing evidence. Int J Neuropsychopharmacol. 2002;5(4):333‐343. doi:10.1017/S1461145702003024

[3]Hizli Sayar G, Cetin M: Psychobiotics: The potential therapeutic promise of microbes in psychiatry, Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical Psychopharmacology 2016;26(2): 93-102.

[4] Bravo JA, Forsythe P, Chew MV, et al: Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve, Proceedings of the National Academy of Sciences of the United States of America 2011;108:16050-16055.

[5] Liu YW, Liu WH, Wu CC, et al. Psychotropic effects of Lactobacillus plantarum PS128 in early life-stressed and naïve adult mice. Brain Res. 2016;1631:1‐12.