by Julia Rucklidge, PhD & Bonnie Kaplan, PhD

Probiotics have certainly become quite the rage across the world for the treatment of all kinds of ailments from irritable bowel syndrome (IBS) to infectious diarrhoea to stress to low mood. Some might say that the enthusiasm has been rather slow to develop. Bonnie remembers reading an article in the 1970s describing the Russian medical practice of always prescribing probiotics for patients being prescribed antibiotics. And who has not read of the (over-simplified?) interpretation of longevity in the Caucasus (Azerbajian, Georgia) being due to their diet of yoghurt. Beginning in the 1970s, Dannon used that association to promote their products in North America.

Recently, the popular press has propagated the idea that probiotics are the next antidepressants, using headlines like “The Mental Health Benefits of Probiotics: ‘Good Bacteria’ May Improve Mood, Fight Depression”, “Are Probiotics the New Prozac?”, “Can Probiotics Improve Your Mood?” to “Could Bacteria Be the Answer to Treating Depression?”

Many of these headlines actually emanate from studies conducted on healthy young adults. For example, Tillisch and colleagues1 provided the first direct demonstration that probiotics can affect brain function in healthy humans by comparing brain activity of 46 women, some who had consumed a fermented milk product with bacteria over a 4 week period and some who had consumed a placebo and some who had received no intervention.  Based on functional magnetic resonant imaging (fMRI), those who had consumed the fermented drink had greater activity of brain regions that control central processing of emotion and sensation than those who had consumed the placebo.

More recently, a randomized controlled trial published in August 2015 that was conducted on a healthy group of 40 people showed that taking a probiotic supplement containing Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus acidophilus, Lactobacillus brevis, Lactobacillus casei, Lactobacillus salivarius, and Lactococcus lactis may reduce cognitive reactivity in these non-depressed individuals over a 4 week period.2 In this study, cognitive reactivity was defined as reactions to sad mood, specifically reduced rumination and aggressive thoughts.

The idea that supplemented probiotic bacteria — “live  microorganisms that, when administered in adequate amounts, confer a health benefit on the host”3; p.58 — could be used as a treatment for depression was brought to our attention by Logan and Katzman.4 The term “psychobiotics” was coined by Dinan and colleagues5 to describe probiotic bacteria that produce health benefits in patients suffering from mental health problems. Indeed, there are many narrative reviews extoling the virtues of probiotics and the potential they hold for reducing inflammation and improving brain function. Animal models have demonstrated that administration of probiotics can affect emotional behaviour. A possible mechanism by which supplemented probiotics may change emotional states is through altering the microbial composition of the gut, limiting production of proinflammatory cytokines (proteins important in cell signalling), and reducing inflammation, which can have clear effects on gut–brain communication.6

The theory sounds great, but does the evidence support the theory?

Given the amount of press that has been given to the topic of probiotics as a potential therapy for depression but also more broadly for psychiatric symptoms, a former PhD student of Julia’s, Amy Romijn, reviewed the literature as part of her PhD program. She was interested in finding out how extensive the evidence base actually was for the use of probiotics for the treatment of symptoms.

She conducted a systematic review, which requires extensive searching through thousands of articles to find the types of trials that are viewed as good quality and have treatment implications. The only articles that were included were  double-blind, randomized, placebo-controlled human trials, that used a standardized, validated scale to assess the effects of probiotic interventions compared with placebo on psychological outcomes, or symptoms of psychiatric disorders.

Surprising to us, only ten trials met the inclusion criteria. More surprising was that it was quite hard to extract meaningful data from many of the trials as not all the statistics had been provided in the publications. Also, due to the huge variability in the quality of the trials, it was hard to extract any meaningful conclusion from the studies we did find. Overall, there were far more trials showing no benefit of probiotics over placebo than positive trials (ie probotics were found to be better than placebo) in all areas assessed (stress, depressed mood, schizophrenia, autism and anxiety).

However, due to the variability in population, method, sample size, duration of intervention period, bacterial strains used, and placebo product used, interpreting the results of these trials cohesively was seriously problematic. The variability in population was a considerable issue, as a majority of studies were conducted in populations which were irrelevant to the topic: e.g. adults with irritable bowel syndrome regardless of mental function (30% of the trials), and healthy adults/healthy smokers (30% of the trials). Only two trials were conducted in relevant populations (one trial in children with autism7 and one in adults with schizophrenia8) and neither showed a benefit of probiotics over placebo on psychological outcomes or psychiatric symptoms.

Amy’s systematic review, which was just published this week,9 concluded:

“Overall, there is very limited evidence for the efficacy of probiotic interventions for psychological outcomes. The evidence base is lacking in completeness and lacks applicability. More trials are necessary before any inferences can be made about the efficacy of probiotics in mental health applications.”

So what does this mean? Well – it’s like anything, the craze seems to come before the evidence. We need to be a little more cautious about believing that probiotics are going to help alleviate psychological symptoms. At this point in time we really don’t know and much more research is required to effectively provide advice to people considering this option for treatment. Having said that, people do get better on probiotics, they just don’t often get better than the placebo group. The question is whether that improvement can be entirely attributed to the placebo effect or not. The jury is still out on this one.

One very important feature of the probiotic research will have to be addressed in future publications: number and quantity of strains. Usually when we write about nutrients, or even medications, we might mention the importance of dose — meaning quantity. But in the probiotic world, there is another facet that requires attention: there are dozens of strains. Do they have different effects? Are some more important than others? And what about prebiotics?

References:

  1. Tillisch K, Labus J, Kilpatrick L, Jiang Z, Stains J, Ebrat B, Guyonnet D, Legrain–Raspaud S, Trotin B, Naliboff B, & Mayer EA. (2013). Consumption of Fermented Milk Product With Probiotic Modulates Brain Activity. Gastroenterology,144, 1394-1401.e1394.
  1. Steenbergen L, Sellaro R, van Hemert S, Bosch J. A, & Colzato LS.  (2015). A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain Behavior and Immunity, 48, 258-264.
  1. Sanders M. E.  (2008). Probiotics: Definition, Sources, Selection, and Uses. Clinical Infectious Diseases, 46, S58-S61.
  1. Logan A. C., Katzman M. (2005). Major depressive disorder: Probiotics may be an adjuvant therapy.  Medical Hypotheses, 64, 533-538.
  1. Dinan T. G, Stanton C, & Cryan J. F. (2013). Psychobiotics: a novel class of psychotropic. Biological Psychiatry, 74, 720-726.
  1. Kaplan, B. J , Rucklidge, J. J, McLeod, K, & Romijn, A. (2015). The Emerging Field of Nutritional Mental Health: Inflammation, the Microbiome, Oxidative Stress, and Mitochondrial Function. Clinical Psychological Science, 3, 1-17.
  1. Parracho HM, Gibson GR, Knott F, Bosscher D, Kleerebezem M, & McCartney AL. (2010). A double-blind, placebo-controlled, crossover-designed probiotic feeding study in children diagnosed with autistic spectrum disorders. International Journal of Probiotics & Prebiotics., 5, 69-74.
  1. Dickerson F. B., Stallings, C., Origoni, A., Katsafanas E., Savage C. L., Schweinfurth B. A., Goga J., Khushalani, S., & Yolken, R. (2014). Effect of probiotic supplementation on Schizophrenia symptoms and association with gastrointestinal functioning: A randomized, placebo-controlled trial. The Primary Care Companion to CNS Disorders, 16, e1-e6.
  1. Romijn A. R., Rucklidge J.J. (2015). Systematic review of evidence to support the theory of psychobiotics. Nutritional Reviews, 73, 675-93.

First published in Mad In America

Bonnie Kaplan, PhD. Bonnie has published on the biological basis of mental health – in particular, the contribution of nutrition to brain development and function, micronutrient treatments for mental disorders, and the effect of intrauterine nutrition on brain development and maternal mental health.
Julia Rucklidge, PhD. Julia’s interest in nutrition and mental illness grew out of her own research showing poor outcomes for children with psychiatric illness despite conventional treatments. She has been investigating the role of micronutrients in mental illness.
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