July 6, 2020

expert reaction to systematic review of prebiotics and probiotics in treatment of depression and anxiety

A study, published in BMJ Nutrition Prevention & Health, looked at prebiotics and probiotics in treatment of depression and anxiety.

Prof John Cryan, Professor & Chair, Department of Anatomy & Neuroscience, and Principal Investigator at the Alimentary Pharmabiotic Center, University College Cork, said:

“Over the past decade there has been increasing interest in the role of the microbiome in playing a role in brain and behaviour. With that our group in Cork have coined the term “Psychobiotic” as a means of improving mental health via the microbiome¹.  This paper is well conducted systematic review examining the potential of targeting the gut microbiota in depression and anxiety.

“The paper concludes that of the 7 studies examined they demonstrated a significant, quantitatively evident, improvement of symptoms and/or biochemically relevant measures of anxiety or depression for probiotic or combined prebiotic–probiotic use.

“There are a number of limitations of course mostly around the infancy of the field. Moreover, the use of the term probiotic which by definition is a microorganism that when taken in adequate amount confers a health benefit and there is a tendency in the field to “lump” all commercially available strains into the same category independent of the level of evidence there is.

“We know that strains really matter, and this review is not able to identify what it is about specific strains that render them with beneficial effects.

“Finally, there is a strong potential for publication bias in the field with very few negative randomized controlled studies published.

“Thus, moving forward as this review highlights there is a great need for longitudinal studies for different psychobiotic strains and diets both as standalone or as adjunctive therapies in anxiety and depression.”

¹Anderson SC, Cryan JF, Dinan T. The psychobiotic revolution: mood, food, and the new science of the gut-brain connection. Washington, DC: National Geographic Press, 2017.

Prof Kim Barrett, Distinguished Professor of Medicine, University of California, said:

“Noonan and coworkers set out to conduct a systematic review of the medical literature to uncover whether there is convincing evidence of benefit for probiotics and/or prebiotics for the treatment of depression and anxiety.  Such beneficial effects have been suggested by a plethora of animal studies, but whether they extrapolated to human patients was unclear.

“The authors identified a large number of papers relevant to their work, but in the end, only seven fulfilled rigorous criteria for inclusion and none of these examined the treatment of anxiety in isolation.  Nevertheless, despite variations in the study populations and the probiotic preparations employed, there was a largely consistent finding that probiotics with or without prebiotics, but not prebiotics alone, had a small but significant effect in reducing quantitative indices of depressive symptoms as well as a chemical that has been postulated to mediate crosstalk between the gut and the brain.  The limitations of the studies, however, include the relatively small number of patients studied, the short duration of interventions, the fact that several of even these highly selected papers showed evidence of bias, and the lack of information about the durability of any effects on depression that were seen.  Nevertheless, interpreted cautiously, this systematic review does imply that larger, well-designed trials of probiotics in depression (and anxiety) might be warranted.  On the other hand, it should be noted that in other areas of medicine such as digestive disorders, as evidence has accumulated, the case for the use of probiotics has actually been mostly weakened rather than strengthened (https://gastro.org/press-releases/aga-does-not-recommend-the-use-of-probiotics-for-most-digestive-conditions/).”

Prof Allan Young, Professor of Mood Disorders, Institute of Psychiatry Psychology & Neuroscience, King’s College London (IoPPN), said:

“The press release accurately reflects the science. This is good quality research but it is a review of relatively preliminary data. So while this systematic review of the research literature supports the notion that pre and probiotics may be helpful for people with anxiety and depression, more research is needed. These data do make a case for larger trials to be carried out.”

Prof David Curtis, Retired Consultant Psychiatrist and Honorary Professor at UCL, said:

“The review reports on a small number of small trials of generally poor quality. Although these published studies claim to show some benefits of probiotics on depression we have no idea whether there were other studies which showed no effect which were not published. Overall, doctors do not believe that probiotics are likely to have much of an effect on mood. People with depression should seek medical advice and not try to treat themselves with dietary supplements which are not of proven benefit.”

Prof Kevin Whelan, Professor of Dietetics and Head of Department of Nutritional Sciences at King’s College London, said:

“This is a review of seven studies using probiotics to treat symptoms in people diagnosed with depression. However, only five of the studies were gold standard clinical trials where the effect of the probiotic is compared with a placebo dummy supplement, and therefore the findings must be carefully interpreted. In the majority of studies there was a reduction in severity of depression in those taking probiotics, which is good news for those suffering from depression.

“The review tells us that in people with depression probiotics may work, however it fails to tell us how much they may work. This is a systematic review but the researchers have not synthesised the findings together into a meta-analysis. So the strength of such a review, whereby the data from individual research studies are statistically added together to estimate the overall size of any benefit, has not been undertaken. This review does not tell us whether probiotics may help a little or a lot.

“Many of the probiotics used in the studies are not widely available in shops. Probiotics often contain different strains of bacteria and we do not know if the supplements, sachets and fermented milks you find on supermarket shelves will work, or only those probiotics used in the research studies.

“Given probiotics were not shown to worsen depression or cause other side-effects, then there is unlikely to be any harm in someone with depression trying probiotics in addition to the treatment recommended by their doctor.

“Most of the studies were conducted in people with depression also using anti-depressant medication. So it is crucial that probiotics are seen as complementary to standard treatments recommended by your doctor, and not as an alternative.”

‘Systematic review: Food & Mood: a review of supplementary prebiotic and probiotic interventions in the treatment of anxiety and depression in adults’ by Sanjay Noonan et al. was published in BMJ Nutrition Prevention & Health at 23:30 UK time on Monday 6^th July.

DOI: 10.1136/bmjnph-2019-000053

Declared interests

Prof Kim Barrett: I have no conflicts of interest to declare.

Prof Allan Young: Project title: Gut Feeling: Understanding the Mechanisms Underlying the  Antidepressant Properties of Probiotics

Principal investigators: Stone, J., Cleare, A., Young, A.

Project start/end dates: 1/10/2018 → 31/03/2022

Funders: Probiotics International Ltd

Total: £ 40,000.00

Prof David Curtis: I have no conflict of interest to declare.

Prof Kevin Whelan: Professor Whelan has received research funding in relation to probiotics from Danone and Nestle. He has received a speaker fee for a lecture on probiotics from Yakult.