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Can probiotic yogurt cure your psychiatric ills?

The views expressed are those of the author and are not necessarily those of Scientific American.


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I saw this paper going around the internet early last week, and I was immediately very interested. After all, right now probiotic yogurt is the yogurt hotness, right up there with greek yogurt (and when they combine the two, someone is going to be very, very rich). Right now people think probiotic yogurt is good for your stomach, but can it also be good for your brain? I was immediately skeptical. But I read the paper, and the data is pretty convincing and with some interesting implications. But while probiotic yogurt certainly doesn’t seem to be harmful and may have some good stuff going on, I don’t know that I’d rely on it to cure your psychiatric ills just yet. We’ve still got a long way to go.


(Source)

Bravo et al. “Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve” PNAS, 2011.

Your brain interacts with the body in interesting ways. I mean, we know that the brain influences the body. But it’s only recently that we’ve begun really to explore how the body influences the brain. For example, the relatively new interaction between the gut and the brain just got more complicated, with the introduction of…your bugs. The little bugs that live in your digestive tract. There is some evidence that the microbes in your gut can influence your central nervous system. But so far the evidence has largely been indirect. Right now we know that changing the gut flora of mice can change things like stress responses, but the major question…HOW.

This is important not just because of the idea of bacteria (however indirectly) controlling your brain. There are many gut disorders (the usual example is irritable bowel) which bring along with them the increased likelihood of a psychiatric disorder such as anxiety or depression. Of course, you’re always stuck with the chicken and egg problem: does your irritable bowel CAUSE psychiatric disorders, or are you showing psychiatric disorders just because you’re in a lot of gastrointestinal discomfort all the time.

And here we come to the question of probiotic bacteria. Probiotic bacteria are the good kind, the kind that live in and populate your gut. They don’t appear to do any harm, and some studies have suggested that they may help with symptoms of irritable bowel. These same studies have also looked at the emotional symptoms that tend to run with irritable bowel, like anxiety, etc, and shown that these symptoms also decreased. But again you have to wonder: are the women (irritable bowel studies are usually done in women) showing fewer anxiety symptoms because their anxiety is decreased by direct actions of the probiotic bacteria? Or are their anxiety symptoms decreased because they don’t feel all bloated and farty all the time? In other words, if the probiotic bacteria are affecting the psychiatric symptoms, we need to know HOW. We need a mechanism.

To look at the effects of probiotic bacteria in mice, the authors of this paper looked with the bacterium Lacobacillus rhamnosus, which is currently the bacteria of choice for the Amerifit Brand that produces Culturelle. They took a bunch of normal mice, and gave half of them broth, and half broth with the L rhamnosus in it, for 28 days. They then ran a series of behavioral tests, and also looked at levels of specific receptor subtypes.

For the behavioral tests, they looked at two anxiety related tests, the elevated plus maze, and the open field, and they used the forced swim test, which is used to look at the antidepressant effects of drugs. In the elevated plus maze, you have a big plus mark, big enough for a mouse to run around in, that’s a few feet off the floor. Two of the maze arms have nice high walls, and two are just a platform. The mouse likes dark and enclosed spaces, and prefers to stay in the closed arms. Mice who are especially anxious will spend even more time in the closed arms than those who are not. If you give a mouse drugs to make it LESS anxious, it will spend more time exploring the open arms of the maze. The principle of the open field is similar: mice prefer to stay near the darker edges and not in the open area of the maze, but when feeling less anxious will explore more.

In the forced swim test, you put the mouse or rat in a cylinder of water where it cannot touch the bottom. Rodents are good swimmers, and they’ll swim around until they realize there is no escape. At that point they will start to float. But when you give an animal something that is an antidepressant (like prozac) the animal will swim for longer and float less.

In both the elevated zero maze and the forced swim test, the mice with the L rhamnosus in their systems showed less anxiety and more struggle, respectively. In other tests such as fear conditioning, the mice showed less conditioned fear. They also showed a decreased corticosterone response to stress (corticosterone is the stress hormone in mice). So it looks like mice with the probiotic bacteria in their systems show different behavioral responses to stress and less anxiety-like behavior.

Of course then you want to know WHY. After all the brain and the gut are…some distance apart. So the authors looked in the brain, specifically at GABA receptor subtypes. GABA is the main inhibitory neurotransmitter in the brain, which usually serves to decrease neuronal activity. But, as we much always remind ourselves, a neurotransmitter is ONLY as good as its receptor, the protein complex that received the neurotransmitter and changes shape inside the cell membrane to transmit the message inside the next cell. In the case of GABA, there are two major types of receptors: A and B. GABA A receptors, when hit with a GABA molecule, open an ion channel, changing the internal charge of the neuron. In contrast, GABA B receptors, when hit with a GABA molecule, change shape and activate other molecules inside the neuron, in what is called a second messenger system, which can result in a huge cascade of secondary events inside the cell. And each of these receptor types is made up of little modules, receptor subtypes, which combine together to make a single receptor. Changes in these receptor subtypes can change how the receptor functions. And changes in both of these receptor types have been linked to anxiety (GABA A) and depression (GABA B).

When the authors looked at these receptor subtypes, they found that GABA A receptors AND GABA B receptors both had changes in their subtype levels. While there’s no data on what effects these particular subtype changes have behaviorally, it’s an interesting effect, because it means that the difference in the probiotic bacteria in the GUT is influencing the composition of the GABA receptors in the BRAIN. And how do the gut and the brain primarily communicate? Through the vagus nerve.

The vagus nerve is the 10th cranial nerve, and it conveys sensory information from areas like the gut back to the brain (and vice versa). To see if this was the way the probiotic bactera were having their effects, the authors CUT the vagus nerve, fed the mice some probiotic bacteria (or placebo), and checked again.

You can see that when the vagus nerve was cut (the two sets of bars on the right), the L rhamnosus bacteria had no effect on the forced swim test. They found that the GABA receptor changes were also absent when the vagus nerve was cut. This means that the probiotic bacteria may be having their effects on the brain by altering signaling from the vagus nerve.

So it looks like probiotic bacteria change vagus nerve signaling, and this can change receptor subunits in the brain, and in turn change behavioral reactions in mice. So we should all start eating probiotic yogurt, right??

Not so fast. The study has some promising implications, but there are a lot of things we still don’t know. HOW is the probiotic bacteria changing the vagus nerve signaling? By what bacteria mechanism? What do the changes in GABA subunits mean in terms of function? And yes, this was all done in mice. Healthy normal mice, without depression or anxiety. Forced swim test and elevated plus maze are good indicators, and very promising, but they aren’t proof of antidepressant behavior (for example, does this increase neurogenesis? Does it make mice more resilient to stress? What about other antidepressant-like behaviors?). Finally, is this specific to L. rhamnosus? How much of this bacteria do we even HAVE normally? Do people with, say, irritable bowel have less of it? How does this happen? While I think the probiotic bacteria may be able to tell us some interesting things about the relationship between our guts and our behavior, I’m not sure how all this is going to pan out in humans. And I don’t want people eating the probiotic yogurt (or people MARKETING the probiotic yogurt), and wondering why they are still depressed. This is a step in the right direction, but until we really know the mechanism, though the greek stuff in particular is really REALLY tasty, I wouldn’t be looking to your yogurt to change your life.

Bravo, J., Forsythe, P., Chew, M., Escaravage, E., Savignac, H., Dinan, T., Bienenstock, J., & Cryan, J. (2011). Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1102999108

Scicurious About the Author: Scicurious is a PhD in Physiology, and is currently a postdoc in biomedical research. She loves the brain. And so should you. Follow on Twitter @Scicurious.

The views expressed are those of the author and are not necessarily those of Scientific American.





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  1. 1. scicurious 7:35 am 09/6/2011

    To start this thing off right: I added a bunch of caveats in the original post, but I wanted to clarify one in particular; the role of GABA receptor subunits.

    Right now there is very little evidence for changes in GABA receptor subunit composition in depression related behavior. They found changes in GABA B and GABA A. GABA B receptors have been implicated in animal models of depression, but they did not show any changes with this receptor in the vagovectomized mice. Now this could be because they just didn’t go there, but it could ALSO be because…they didn’t find anything. All the real findings were in GABA A, which has some implications for fear, but none for depression.

    Also, they got REDUCTIONS in GABA B, which they say are consistent with antidepressant actions, but reductions in GABA B are ALSO seen in actual MODELS of depressive behavior. So while I think the GABA B data is interesting, I’m not sure how consistent it is, and I’m more impressed (and I think they are too) with the GABA A data, which is much more linked to anxiety and fear conditioning than depressive behaviors.

    Poor authors, because most of the coverage kind of glossed over the fear and anxiety like behaviors (I wonder if this is partially because fear conditioning is not easy to describe, it’s not very nice to the mice) in favor of the depressive-like behaviors, for which there is much less evidence, some of which to me seems contradictory.

    This comment cross-posted to the Scientopia Comment thread.

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  2. 2. kclancy 7:40 am 09/6/2011

    You know Sci, this makes me think of those tag-team posts we did on PMDD and GABA. It seems like lots of people are into GABA for anxiety. But there are significant sex differences it would be worth looking into, since progesterone impacts GABA, so there are lots of mechanisms that could lead to modulation of GABA receptors. Probiotics could be one… and if probiotics could be one then prebiotics (fiber) could as well.

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  3. 3. scicurious 7:44 am 09/6/2011

    Oooh YES! And you know…this was all male mice. They almost never do sex differences in papers like this, unless the sex differences are a paper on their own. It’s really too bad! Especially considering the much higher reported rate of gastrointestinal disturbance in women as well as the higher rates of depression (and possibly anxiety? I’d have to look that up).

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  4. 4. Wailer 2:57 pm 09/6/2011

    Is this bacteria specific or are there the same or similar effects with other bacteria? I’ve seen some studies with other bacteria and they showed similar results on mental health but I don’t know if they function in the same way.

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  5. 5. DaveG 4:53 pm 09/6/2011

    When the relaxed mice are eaten by cats, are the probiotic benefits conferred on the new host? Good deal for the bacteria.

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  6. 6. Cabel 6:23 pm 11/22/2011

    i wonder how this compares to studies of rats on other anxiolytics. does this make probiotic yogurt addictive?

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  7. 7. DimitriAus 7:05 pm 05/10/2012

    Why not take pure probiotics – 100 times more potent? Unless you want to sell a lot of yogurt. Isnt yougut has more milk, sugar and food aditives then probiotics?

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  8. 8. globalee 9:47 am 08/7/2012

    Hmm yhea why yogurt, why not a really good probiotic such as this http://www.novadetox.co.uk/acatalog/lb17-probiotic-capsules.html

    17 strain probiotic pure live probiotics, I really struggle to belive that eating yogurt would have a significant impact on your mental health or for that matter effectivly benefit someone suffering from IBS.

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