Probiotics for the treatment of depression

In a study published in April 2018, researchers looked at the effects of probiotic and prebiotic supplementation compared to placebo in people with Major Depressive Disorder in a double blind, randomly controlled trial (RCT) lasting 8 weeks.

Study results showed those taking the probiotics had a greater decrease in depressive symptoms according to their Beck Depression Inventory (BDI) scores compared to placebo and prebiotics, which had no significant decrease.

The study used the BDI, a standardised mental health questionnaire alongside kynurenine/tryptophan ratios and tryptophan/ branch chain amino acids (BCAAs) ratios.

Using a standardised BDI or equivalent is pretty normal in studies looking at mental health, as it helps determine a baseline for such complex health conditions such as MDD that can be compared and contrasted to other participants and at the conclusion of the study to help determine the effectiveness of treatments. Using a BDI alone to measure outcomes on a study can invite criticism of a placebo effect, as the study participants, no matter the treatment, may feel that they are improving even without receiving an active treatment. The BDI alone can show this feeling of improvement.

What’s truly exciting about this study is the integration of the analysis of kynurenine/tryptophan ratios and tryptophan/BCAAs ratios! Go Biomarkers!

I know that to most, these terms may be unfamiliar. These specific amino acids have been linked to the synthesis of serotonin, our “happiness hormone”. What’s also very exciting is that other studies have shown that disturbances in our gut microbiome can influence the development of depression, the regulation of the synthesis of serotonin and limit the degradation of tryptophan to kynurenine.

By including these amino acid ratios in their study, the researchers have reduced the attribution of improvement of symptoms to placebo effect, as a participant cannot influence these biomarkers.

In brief, tryptophan can either synthesise into serotonin or degrade into kynurenine. Both processes are normal, but when the ratio of tryptophan/ kynurenine is not optimum, the levels of serotonin in the body can drop, leading to an imbalance that can result in an abnormally low level of serotonin. Probiotics push tryptophan to make serotonin and reduce the activity of enzymes that would cause it to degrade into kyurenine.

BCAAs and tryptophan both compete for the same transporter across the blood brain barrier with tryptophan, meaning that if the ratio between BCAAs and tryptophan is also not optimal, the brain will not be receiving amino acids in the right ratios. The study found a decrease in the ratio between the specific BCAA, isoleucine and tryptophan in the probiotic group compared to a less significant decrease in other BCAAs in the prebiotic group and no significant change in the placebo group.

Why is this exciting? Because there is something we can do, with the right probiotics!

The study used strain and sub-type specific probiotics that have been associated with improvements in animal behaviour and improvements in psychological conditions in humans. The strains included Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 CNCM I-3470 at greater than 10x10^9 CFU, once per day.

Other studies have taken place that used non-specific strains of probiotics and found no significant improvement in MDD.

It’s important to be prescribed the right probiotic for you; generally speaking, practitioner brands of probiotics have higher numbers of live bacteria and come in doses and strains that are not available 'off the shelf'.

This study paves the way for further studies, looking at fecal microbiome composition, potentially uncovering more strains of probiotics that may be beneficial, what colony numbers they should be in and with the addition of biomarkers in these kinds of studies, clear treatment protocols can be developed.

How do we nurture our microbiome?

  • Appropriate probiotic
  • Insoluble fibre rich diet
  • Reduce inflammation in the bowel
  • Improve quality of the diet
  • Reduce stress

Study discussed: Kazemi A, et al., Effect of probiotic and prebiotic vs placebo on psychological outcomes in patients with major depressive disorder: A randomized clinical trial, Clinical Nutrition (2018), https://doi.org/10.1016/j.clnu.2018.04.010

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