Can Probiotics be Used for the Treatment of Mental Health Problems?

Julia Rucklidge, PhDBonnie Kaplan, PhD
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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 bifidumBifidobacterium lactisLactobacillus acidophilusLactobacillus brevisLactobacillus caseiLactobacillus 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?

* * * * *

For more information see
Systematic Review of Evidence to
Support the Theory of Psychobiotics

in Nutrition Reviews.

Further reading:

1.  Tillisch K, Labus J, Kilpatrick L, Jiang Z, Stains J, Ebrat B, Guyonnet D, Legrain–Raspaud S, Trotin B, Naliboff B, Mayer EA. Consumption of Fermented Milk Product With Probiotic Modulates Brain Activity. Gastroenterology. 2013;144:1394-1401.e1394.

2.  Steenbergen L, Sellaro R, van Hemert S, Bosch JA, Colzato LS. A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain Behavior and Immunity. 2015;48:258-264.

3.  Sanders ME. Probiotics: Definition, Sources, Selection, and Uses. Clinical Infectious Diseases. 2008;46:S58-S61.

4.  Logan AC, Katzman M. Major depressive disorder: Probiotics may be an adjuvant therapy. Medical Hypotheses. 2005;64:533-538.

5.  Dinan TG, Stanton C, Cryan JF. Psychobiotics: a novel class of psychotropic. Biological Psychiatry. 2013;74:720-726.

6.  Kaplan BJ, Rucklidge JJ, McLeod K, Romijn A. The Emerging Field of Nutritional Mental Health: Inflammation, the Microbiome, Oxidative Stress, and Mitochondrial Function. Clinical Psychological Science. 2015:1-17.

7.  Parracho HM, Gibson GR, Knott F, Bosscher D, Kleerebezem M, McCartney AL. A double-blind, placebo-controlled, crossover-designed probiotic feeding study in children diagnosed with autistic spectrum disorders. International Journal of Probiotics & Prebiotics. 2010;5:69-74.

8.  Dickerson FB, Stallings C, Origoni A, Katsafanas E, Savage CL, Schweinfurth BA, Goga J, Khushalani S, Yolken R. Effect of probiotic supplementation on Schizophrenia symptoms and association with gastrointestinal functioning: A randomized, placebo-controlled trial. The Primary Care Companion to CNS Disorders. 2014;16:e1-e6.

9.  Romijn AR, Rucklidge JJ. Systematic review of evidence to support the theory of psychobiotics. Nutritional Reviews. 2015.

16 COMMENTS

  1. Research or not, for me probiotics were essential to clearing my head and alleviating heart anxiety. It was recommended to me by a medical intuitive about 10 years ago (I think this was before it was ‘a craze’) as I was healing from medication toxicity, and the results were immediate and life-changing. I’d never heard of probiotics before this.

    • Me too Alex…absolutely essential. As usual those of us who are busy getting healthy can’t wait around for the research. Our bodies are wonderful instruments which will guide us to even the right strains of probiotics just for us…imagine that! It’s certainly my experience. It takes time and attention to learn to listen but the body is a wonderful guide. I can feel probiotics…almost communicate with them really. They are truly little beings that populate our guts and help or hinder us…it’s a very good thing to get to know them if we want to get healthy.

  2. I’m going to put in the minority opinion. I think large-scale research on probiotics is likely a waste of time and resources.

    The discussion above already suggests that looking through the file drawer reveals little difference compared to placebo for most trials of probiotic “treatments”, whatever life problems they are treating. That suggests to me that their effectiveness if any is not likely to have a large effect size. It doesn’t mean no more research should be done, but suggests that these treatments aren’t anything to get excited about.

    As we know, resources are scarce and money/time invested in certain “treatments” means other interventions do not get researched. For example, hundreds of billions of dollars have been invested to develop ineffective, damaging neuroleptics to treat psychotic states. This means that few trials of psychotherapy with psychotic people have been done done, and peer support groups, respite centers, group therapy etc. were not researched nor funded.

    I’d guess that the driving force behind research on probiotics is from drug companies that want to monetize it and profit whether or not it has significant benefit to people’s mental health, as long as they can fake the data. At least probiotics would presumably come without all the bad side effects of neuroleptics.

    But still, in my opinion, probiotics research is likely a dead end, small return endeavor. To me the money allocated to it would be better invested in research into individual therapy, family psychotherapy, peer support, job training, and other social programs

    Loving supportive human relationships are the alpha and the omega of recovery from mental health problems, and they are always going to be far more effective than probiotics; thus scarce resources should be redirected towards them.

    • I think, in reality, research of any kind in this field is completely secondary to individual needs. Healing is based on how each of us responds to anything.

      True, love is a universal healer and loving support is vital to allowing healing to occur for just about anyone, but human relationships cannot be forced, and certainly, we cannot manipulate people to love us, trying to do so is one of the things that leads to madness. Right now, loving support in any capacity is what seems to be more scarce than anything in the world.

      We can show ourselves loving support, however, by taking care of our own bodies. That will be different for everyone. And I agree, research for how each individual takes care of their body is a rabbit hole of wasted energy and resources. Not only are we each different, but we also change constantly, so what was relevant yesterday may no longer be relevant today.

  3. Well said, Alex. Since Alex raises the point of medical toxicity, one obvious avenue of research (an avenue that is not likely to get any funding from big Pharma) is how, exactly is gut or intestinal health negatively impacted by psychiatric drugging? Even if pro biotics do not end up delivering a miracle cure for a host of emotional and mental symptoms, at least they may prove to be useful agents in the restoration of one’s personal ‘baseline’ after one’s health has been severely eroded or worsened by psychiatric drugging. Does that make any sense? I’m not sure how to word that thought but many of us would simply like our loved one to get back to their ‘baseline’ after their mental emotional state was made much worse by psychiatric drugging. If pro-biotics have a role to play in that process, bring em on! At least they are sure to do know harm and they can taste delicious!!!

    • Yes, that’s exactly how they worked for me, they restored gut health, the baseline, so that other healing process could happen. The meds did, indeed, destroy my inner ecology, and the probiotics were essential in restoring this. After 10 years of making them part of my daily diet, my gut health is excellent, as is my overall health. I credit the probiotics for the upgrade in physical health, no doubt.

      There is no ONE THING that works, it is a network of healing that occurs. The probiotics restore gut flora/inner ecology to a healthy and nourished state, which leads to a cooling of the system (Chinese Medicine), and this relaxes the heart and mind. It also boosts autoimmunity, so we go into self-healing mode with a healthy gut.

      There is more work to do in healing, aside from this, but the probiotics really took it up several notches, so the healing path became much clearer.

  4. One of the concerns I have with just using a probiotic supplement is that they tend to carry only a few different strains of beneficial bacteria but there are upwards of a thousand different types of bacteria. When we are adding just a few strains as a supplement we ignore hundreds of others.

    As an herbalist I support using fermented foods and bitter herbs that generally promote good intestinal flora without specifically focusing on similar probiotic strains. It’s also important to note what Madmom said…which is that psychiatric drugs impact gut health adversely, (as well as antibiotics) so we engender worse intestinal and mental health with prolonged chronic use.

    The use of fermented foods and bitter herbs (chicory, dandelion, burdock, angelica, dock) are time honored ways of improving digestive health which in turn improves emotional wellbeing.

    • fermented foods and supplements both have been helpful for me. for three years my sensitivities became so severe I couldn’t tolerate fermented foods OR probiotic supplements. I needed to heal my nervous system first which was a challenge because a healthy nervous system relies on a healthy gut!! I was in a catch-22…I used herbs to get my nervous system in a bit better condition and then I tolerated supplements BEFORE I tolerated fermented foods…I continue to use both foods and supplements because I need both at the moment. As my health continues to improve these needs will continue to evolve…anyway…just pointing out that individual needs are going to vary and in some instances supplements are very important.

      In general I’m the get everything from real whole foods gal but there are times that targeted supplementation (not just with probiotics) is critical…usually for periods of time, not forever.

      • oh, another point about supplements. We can know exactly what we’re getting. When folks are hypersensitive we can feel the difference between probiotic strains. Some may trigger us while others don’t. For example being that I’ve had histamine issues I needed to find histamine degrading or histamine neutral strains rather than ones that further create histamine. I can’t control what is in a food ferment…I can know very well what it in a supplement. This knowledge is very helpful. As I am able to take in more and more probiotics my sensitivities are diminishing…I believe it’s related. 🙂

  5. I’m all for this and research into other less expensive, safer, more humane ways of handling distress. Yes, psychosocial programs are important, but I think an exclusive focus on psychosocial factors ignores the fact that severe emotional distress can cause physical problems, and can also be the result of physical problems (at least in part). When I was deeply psychotic, I had major skin problems and hair loss. Part of recovering, for me, was getting these and other physical maladies under control along with my distress. For me, that meant Orthomolecular, which has been absolutely wonderful for me. Other people prefer different forms of healing and health-boosting. I think one wonderful thing about alternative health is that its not as controlled by experts, so there’s a kind of do-it-yourself aspect to the process. For people (“patients”) who have seen and experienced the worst the medical establishment has to offer, that can be very empowering.

    • “I think one wonderful thing about alternative health is that its not as controlled by experts, so there’s a kind of do-it-yourself aspect to the process. For people (“patients”) who have seen and experienced the worst the medical establishment has to offer, that can be very empowering.”

      True, beautiful, and healing.

  6. There is so much research on the topic it is just crazy. The scientists from McMaster University wanted to test how the gut microbiome affected stressed mice. The results have been published in nature communications in regards with gut and depression I highly recommend everyone read the researched paper. The problem with us today is that we get prescribed antibiotics for every tiny little thing and thus the need of probiotics to increase the good bacteria in the gut. As the great saying goes its all in the GUT. Recently, Eric Bakker from New Zealand did an amazing video/lecture in regards with probiotics and I think everyone should be educated and taught the difference between the two, the goods and bads of each. For those of you interested in watching his video just go to youtube search eric bakker probiotics vs antibiotics or check this link https://www.youtube.com/watch?v=MoM-zpq1zQk

    @Jonathan Keyes

    I have done tons and tons of research and I have found out that most strains are useless the really beneficial one is DDS-1 strain by Dr. Shahani, its numerous patents and has been studied for years.

    Regards
    Olga

    • I’ve not used that strain and certainly having a lively mix of multiple strains that our particular bodies like is very important. Again…the research cannot possibly figure out what every particular body needs nor can it research all the many thousands of different strains. Also the idea of patenting bacteria is rather ludicrous…

      The DDS-1 strain you’re is a strain of acidophilus…and acidophilus is a very friendly strain for most people and it’s almost always part of yogurt, for example…(generally an unpainted variety 😛

      But we need a whole lot more than just acidophilus in our guts if we want them to be happy. There are a lot of strains that have lots of research. I found one that was very helpful to me that way. L-plantarum. It’s in many supplements and it’s also naturally occurring in many veggie ferments.

  7. That is a great initiative to actually analyze all the papers on the topic. There’s a lot of garbage papers out there and anyone who sieves through it to produce a conclusion is doing awesome work, even if it may feel hard and ungrateful.

    I believe that right bacterial flora is vital to one’s health but the interaction between our bodies and our second bodies (we have more bacterial cells in our guts than our actual cells) is so complicated it’s really hard to know anything for sure at this point. But it’s somehow good to know that you have you little microbial friends to help you digest and fight of invaders. Makes one feel less alone ;).