Probiotics and cognition

Calvin: "I wish I could just take a pill to be perfect and I wish I could just push a button to have anything I want"
Hobbes: "The American Dream lives on"
Calvin & Hobbes, Bill Watterson


The dream Hobbes refers to is, of course, shared by many outside of the United States. There is an obvious demand for dietary supplements that can improve health in some way. Given the general lack of adverse side effects, probiotics represent an attractive opportunity for improving health.

Previous research has indicated that consuming a fermented milk product with probiotic can alter a network of brain regions associated with emotional-as well as visceral-processing. Sadly, the article did not report how people performed on the task the researchers used. As this task just involved classifying emotions on faces, I suspect that maybe performance was too close to ceiling to demonstrate an effect of the probiotic.

As noted in a recent post, we found that participants reported less stress over weeks of consuming probiotic compared to a strain of Bifidobacerium longum. Interestingly, we also found that participants performed best at a test of visuospatial memory after having consumed the probiotic strain. This particular memory test we looked at (paired associates learning) is dependent upon the hippocampus, a region of the brain that can be affected by cortisol secretion following stress. It may thus be the case that a lower level of stress may account for the improved performance on the memory test.

We also assessed electroencephalography (a method of measuring brain activity via electrodes placed on the scalp), and observed that there was enhanced activity at frontal regions following probiotic consumption, consistent with improved memory. This is not just another way of showing what had already been demonstrated with the participant's memory performance, as frontal processing is associated with top-down processing (i.e. processing relating to motivation and broader context, as opposed to bottom-up/driven by the sensation or perception).

However, the picture is complicated by a more recent study from our group seeking to show similar effects with a different probiotic strain; the results here did not indicate effects on cognition (or stress), despite the fact that we used the same assessments, and despite very promising initial results in animal models with this second bacteria. It thus seems to be the case that specific effects go with specific bacteria. Perhaps we are just at the beginning of understanding how gastrointestinal health can be harnessed to improve brain health.

John R. Kelly, Andrew P. Allen, Andriy Temko, William Hutch, Paul J. Kennedy, Niloufar Farid, Eileen Murphy, Geraldine Boylan, John Bienenstock, John F. Cryan, Gerard Clarke, Timothy G. Dinan, (in press). Lost in Translation? The potential psychobiotic Lactobacillus rhamnosus (JB-1) fails to modulate stress or cognitive performance in healthy male subjects, Brain, Behavior, and Immunity. doi: 10.1016/j.bbi.2016.11.018.

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Probiotics and stress

With the increased research interest in the interactions between the brain and the gut, people are curious whether we can affect the brain in desirable ways by targeting the gut. Existing evidence from France has indicated that taking a probiotic can reduce psychological distress and urinary levels of cortisol (a hormone associated with stress).

Previous research from our own group in animal models indicated that a strain of bacteria-Bif. Longum 1714-could reduce the physiological stress response. The 1714 strain was associated with reduced stress-induced hyperthermia, as well as reduced depression-like behaviour. Given these findings, there was interest in whether the bacteria could have similar stress-reducing effects in humans.

Participants took the probiotic for 4 weeks and the placebo for 4 weeks. (Both came in the form of a white powder that one mixes into milk each morning). Participants filled in daily online questionnaires assessing their perceived stress levels-during probiotic supplementation stress levels started off at a similar level, but were reduced by the final week of taking the probiotic.

So far, the results were similar to what the group in France found. But we took things a step further by seeing how people would respond to a controlled stressor after taking the probiotic. At baseline and following each of the 4 week periods they were exposed to a socially evaluated cold pressor test. One has to immerse one's hand in ice cold water for up to 3 minutes. After taking the probiotic, participants showed lessened cortisol output in response to the stressor. Furthermore, although anxiety levels were heightened by the stressor at all visits, the increase was lessened following the probiotic.

Interesting stuff, but further research will be needed to determine how the bacteria is having these effects-we know that bacteria can produce neurochemicals that affect factors such as mood, but we're still in the early days of trying to work out the process through which this leads to knock-on effects on the brain.

We have presented the findings at conferences such as Neuroscience Ireland and Society for Neuroscience (you can download the relevant posters from the Department of Psychiatry website) and the results  have received coverage in numerous mainstream outlets, including The Guardian and The Huffington Post. As usual, things move a bit more slowly in academia, but we have the research paper out now too-it's open access, so anyone with an internet connection can access it:

Allen, A. P., Hutch, W., Borre, Y. E., Kennedy, P. J., Temko, A., Boylan, G., Murphy, E., Cryan, J.F. Dinan, T.G., & Clarke, G. (2016). Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers. Translational Psychiatry, 6(11), e939.

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