Aug 26 2013

Probiotics for Mental Health?

I frequently criticize science journalism for falling into one or more common traps – false balance, hyperbole, misleading framing, failure to put one study into the proper context, inappropriate extrapolation, and others. Here is one article discussing the relationship between gut bacteria and mental health that can be used as a textbook example of how not to write a science news story.

The article begins, as is unfortunately often the case, with an emotional anecdote. Journalists are taught to find a human angle to draw the reader in, and I get this. But this style is better suited to fluff pieces than serious science journalism.

There are multiple problems with this style as applied to a science topic. The first is, of course, that the story is anecdotal. We cannot know what the implications of this story are. It is likely highly selected – chosen out of many possible examples to be the most dramatic and emotionally appealing example of whatever story the journalist wants to tell.

In this case we are told the story of Mary who has severe refractory obsessive compulsive disorder (OCD). All the emotional hooks are there – her parents are desperate, all previous treatments have failed, and the doctor they are seeing (the focus of the piece) is their last hope.

The doctor, James Greenblatt, is presented as a maverick, almost a guru, who sees something no other doctor has seen. His ideas, specifically that gut bacteria are a major contributor to mental illness and can be treated with probiotics, are treated as prophetic, ahead of their time, and that they are in the process of being validated, which at this point is almost just a formality.

His treatment consists of drugs, therapy, and probiotics, but of course the probiotics get the credit for any improvement, which is described by the journalist as “miraculous,” thus completing the standard medical anecdote formula. In case you missed it, here is that formula:

- Sick patient no one can figure out or successfully treat
- Desperate family/parents
- Maverick doctor with unusual treatment ideas
- Miraculous response to treatment
- Reporting of preliminary and cherry picked research as if the conclusions are inevitable or obvious
- Token skepticism optional.
- Finish with an emotional flourish that immediately negates the token skepticism.

This is fluff journalism inappropriately applied to science topics typically by people who are not trained science journalists.

Probiotics for mental health

What about the topic itself – does the bacteria that colonizes our GI system have a dramatic effect on brain function, including mental illness? At present this is an intriguing idea with some promise and preliminary evidence, but that’s all. It is very unlikely that intestinal flora have as much impact as the article suggests, and there are numerous other factors that are well established, such as genetics and environmental factors.

The research cited in the article is mostly animal research, which essentially shows that mice with certain GI flora have higher levels of stress hormone. That is a plausible simple mechanism – increased levels of cortisol raise the overall level of stress, which could exacerbate things like OCD or anxiety. Exacerbating a pre-existing condition is not the same as causing that condition, however. Even this relatively simple effect is not established in humans, who, it turns out, are not mice. (Animal research is legitimate, but caution is always recommended in extrapolating to humans, especially in psychology studies.)

Some of the studies also do not use probiotics but fecal transplants to reconstitute the gut biome of the mice being studied. This cannot be extrapolated to probiotic use (I’ll discuss this more below).

The article author, Carrie Arnold, mentioned one human study, although the link she provided was to the wrong study. I did manage to track down the study to which she referred – a study in women exposed to fermented milk with four probiotics, milk without probiotics, and no intervention (number of subjects in each group 12,11,13 respectively). They found that emotional response to faces as measured by fMRI was decreased in the probiotic group.

The usual caveats apply – this was one study, the sample size was very small, and fMRI scans (functional magnetic resonance imaging) is a tricky technology that requires great care and controls, and lots of averaging to get a signal out of the copious noise. No reliable conclusions can be drawn from one small fMRI study.

To summarize – the state of the research is very preliminary, mostly involves animals, the one human study is small and not much can be concluded from it, and often the interventions are more extreme (fecal transplants) than simply taking a probiotic product. Also the outcomes are difficult to interpret and we may just be seeing basic physiological effects on the brain.

For example, I already mentioned stress hormone activity. Gut bacteria might also plausibly affect glucose metabolism, or  aspects of the endocrine system such as pituitary function. What this means is that gut bacteria likely do have a primary effect on some basic physiological functions of the body, which in turn can secondarily affect brain function in terms of mood,  anxiety level, and other basic emotions.

The evidence does not point to a direct effect of gut bacteria on brain wiring or function. It can be explained more simply as just the brain responding to the physiological environment of the body (nothing new or surprising). Some of the results may be as simple as animals being in a bad mood when their tummy aches, but I’ll grant that it’s likely there is more to it than that.

Even if we grant that the constitution of bacteria in the GI system has an indirect effect on stress, anxiety, and emotions it still remains to be seen if current interventions have a significant effect on the GI flora. The evidence so far warrants caution. Mark Crislip wrote an excellent review of this topic on science-based medicine. In short, the species of bacteria that make your GI system their home exist in a stable ecosystem. It is very difficult to alter that ecosystem by adding one or a few probiotic species. The new species simply get edged out by the established species., and the existing equilibrium is maintained.

Therefore, if we do discover a relationship between GI flora and mental health, we currently don’t have the knowledge or technology to do much about it.

All of this means that existing probiotic products and interventions are very  unlikely to have a significant effect on the treatment of any mental health issue. In any case, there are no clinical trials demonstrating the efficacy of probiotics in mental disorders. Especially given the preliminary and implausible nature of the basic science, such definitive clinical efficacy trials would be needed before any health benefit claims for specific probiotic products would be justified.

In contrast, Carrie Arnold characterized the situation with this paragraph – easily the worst in her piece:

Although plenty of questions remain, the benefits of using probiotics to treat human behavior are becoming increasingly obvious. Yogurts like Dannon’s Activia have been marketed with much success as a panacea for all of our intestinal ills. Other probiotic supplements have claimed to support immune health. Probiotics’ potential to treat human behavior is increasingly apparent, but will manufacturers one day toss an anxiety-fighting blend into their probiotic brews?

She is essentially using marketing claims to justify the scientific conclusion that the benefits of probiotics are “increasingly obvious.” This, of course, is absurd and flies in the face of recent history. Antioxidant claims, for example, vastly exceeded the evidence and now it seems that the hype of antioxidants was entirely misguided. Such marketing claims (especially in the unregulated market of supplements) tend to be premature, over-hyped, and ultimately wrong.

Conclusion

When I write about probiotics I always feel compelled to point out that I have nothing against the concept. I actually think that we are at the early stages of discovering that the bacteria that are symbiotic with humans play a large role in our health. They are therefore potentially a useful area of research to explore this relationship, and figure out ways to improve health by altering the bacteria that live on and inside us.

Like any single approach to health or new technology, however, early hype tends to vastly exceed the reality. What is likely to be just one more complex and limited tool in our box is talked about as if it will be a panacea. While scientists are still trying to figure out the “ifs,” the sensationalist media is presenting future scientific knowledge as if it is inevitable and already known. The point of research is not to demonstrate that something is true but to ask if it is true, and until that research is done, we truly do not know. Further, most new ideas tend not to be true, or to be far more limited than initial enthusiasm would suggest.

This is now a common pattern. In the decade or two when a new scientific idea in medicine is being worked out, and may or may not pan out as a good idea and successful treatment, the hype surrounding this new idea is exploited to sell snake oil. Stem cells are an exciting idea, but current stem cell clinics are fraudulent. Antioxidants were an interesting idea for an intervention, but as our knowledge deepened it became apparent that they were more of a double-edged sword than elixir of life. Viral vector gene therapy will likely be an important treatment option, but the technology has proved trickier than we imagined, to the tune of decades of further research.

Probiotics are still in this early phase as well. Existing treatments and products, according to the research currently available, range from worthless to perhaps having a minor benefit in certain specific situations. This is a useful area of research, but it remains to be seen what the ultimate potential of probiotic therapy will be, what level of interventions will be required, and how long this will all take.

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12 responses so far

12 Responses to “Probiotics for Mental Health?”

  1. evhantheinfidelon 26 Aug 2013 at 1:26 pm

    My mother buys me Kefir to help with gut problems that are probably the effects of anxiety. I told her that the probiotics probably didn’t help my gut, but I like the taste of the stuff anyway. It would be nice to think that the probiotics could help with me anxiety, but alas, it seems it isn’t so. I have a question, Dr. Novella. What state is our knowledge in in regards to the cultures in our body that are important, and many they number? Does it vary from person to person?

  2. daviddb1on 26 Aug 2013 at 1:28 pm

    I was thinking about emailing this story to you. I just read it yesterday myself. I love the Verge, but this article really bugged me. My favorite part of the article, which you mentioned as well, was: “besides psychotherapy and medication, Greenblatt also prescribed Mary a twice-daily dose of probiotics,”. HA! Besides real therapy, we also….. Anyway, glad to see you found it and made a point to address it. I hope you don’t mind if I add a link to this blog post on the comments of the article. There is too much BS being spread in those comments.

  3. denisexon 26 Aug 2013 at 7:51 pm

    From my own negative experience I’m wondering if there’s even good evidence that probiotics help with digestive problems as widely claimed.

    I’m on my fourth bottle of increasingly more expensive pills trying to recover from antibiotics taken almost a year ago.

    It struck me to wonder when I first saw the Activia commercials why they would recommend that you eat this stuff every day; once the bacteria have colonized your gut, why should you need to keep taking it? I went looking to see if they might have engineered these bacteria not to reproduce. I didn’t see anything like that, but I did see that there’s a lot of uncertainty about whether probiotics taken orally even survive the trip down to the gut at all. Maybe that would explain why none of these pills has helped me.

  4. tmac57on 26 Aug 2013 at 8:58 pm

    denisex- I’m no expert about this,but I am going to go out on a limb and say that bacteria will indeed survive the trip down to the gut because otherwise we would never have any problem from dangerous strains of e coli (and others) that regularly cause dangerous outbreaks of food borne illnesses (it’s always the organic bean sprouts ;) ) .
    My understanding of the state of probiotics is that they have identified a handful of gut flora that are common to most people,and posit that replenishing those specific types may help recolonize missing bacteria (if indeed they are missing). And that may be true,but that is no substitute for the specific gut flora that is likely to be unique to the individual,due to whatever factors have come to shape their personal microbiome.

  5. Cow_Cookieon 26 Aug 2013 at 9:26 pm

    Novella wrote: “The article begins, as is unfortunately often the case, with an emotional anecdote. Journalists are taught to find a human angle to draw the reader in, and I get this. But this style is better suited to fluff pieces than serious science journalism.”

    Don’t confuse bad use of a structure with a perfectly fine structure. A good journalist could use this format with someone who accurately reflects the evidence and achieve remarkable results.

    You still need the human angle to grab readers who wouldn’t otherwise read it (sad but true). The key is finding a subject who is representative of the whole rather than just individually compelling.

    Good nonfiction of any kind is about the transition from anecdotal to global. The average reader just isn’t going to relate to pure stats and numbers. Instead, you use the anecdotal narratives to support and illuminate the larger truth. There’s nothing inherently wrong or “fluffy” about this as long as the anecdotes support the evidence.

    Rick Atkinson’s “The Guns at Last Light” is an excellent example of this. It’s a history of the invasion of Western Europe. In one paragraph, he quotes intensely personal letters from soldiers who died in the campaigns. In the next, he cites mind-boggling statistics about the amount of supplies used. From that dialogue between the tactical and the strategic, the reader gains a larger understanding of what the war was about. And without either of those parts, the book wouldn’t have the emotional or intellectual heft that it does.

    Good science journalism works the same way.

  6. BillyJoe7on 27 Aug 2013 at 12:27 am

    “the species of bacteria that make your GI system their home exist in a stable ecosystem”

    I seem to remember an article here or at SBM that said the opposite – that our biomes are ever changing.

  7. ccbowerson 27 Aug 2013 at 9:57 pm

    tmac57-

    The pH of the stomach is 1-2, so assuming normal function (no reason for reduced acid secretion like a PPI) most bacteria will be killed, unless they can tolerate very low pH like encapulated forms. Diarrheal symptoms like those caused by some strains of E coli you mentioned are the result of enterotoxins produced by the bacteria. It is not necessary for the bacteria to survive to cause illness, because the toxins themselves are causing symptoms.

    Now, there are ways to make sure that bacteria survive by using delayed release formulations, such as enteric coatings. For example, putting the bateria in a capule that remains intact at low pH (stomach), but dissolve in higher pH settings like the small intestine and beyond. Of course, very few probiotics have been shown to have any major effects for many reasons (discussed above and elsewhere). The one exception appears to be fecal transplantation for C diff, which can be given orally (as delayed release), but is usually given by enema infusion for obvious reasons.

  8. lindyblueon 30 Aug 2013 at 5:27 pm

    I seem to remember hearing a story about this on Radio Lab a while back. They mentioned something about stimulating the vagus nerve, I think? Anyhow, if I recall correctly, their reporting was more balanced and did talk about how there’s still much more researched required though did seem a little hyped but nothing close to this. It’s been a while since I’ve listened to it though, and I may have to go back and relisten.

  9. lindyblueon 30 Aug 2013 at 5:28 pm

    *research, not researched

  10. dcardanion 05 Sep 2013 at 6:32 pm

    I had an issue that was helped by probiotics, and I have to say that I think this comment you made in the article is spot on:

    “Some of the results may be as simple as animals being in a bad mood when their tummy aches”

    It goes way further than that! Having a digestive issue 24/7 means constantly being vigilant about how close you are to a bathroom at all times, losing sleep because it wakes you up several times a night, not feeling like going out, or eating, or being with people, or being around loved ones. It’s kind of like torture. Taking a pill that clears that one problem up can surely go a long way towards fixing depression, though probably not because it directly affects the brain!

  11. Tro10on 13 Sep 2013 at 6:41 pm

    I just came across your blog because I think that the research on probiotics is intriguing, but like all new research things will get blown out of proportion by journalists driven by the faddish dictates of the market rather than the slow paced demands of scientific integrity. That said, I was speaking with a friend who has a terrible time with antibiotics — both he and his mother goes through a pretty bad depression for several days when they take them. Of course, there are a myriad number of possible explanations, but after hearing about Greenblatt’s research, I couldn’t help but wonder if there was a connection between the dead critters in his gut and his depression…

  12. brotherjohnon 24 Sep 2013 at 2:21 pm

    Wow, you think THIS story was bad, take a look at the subsequent ABC News Story (from Sept 12th): http://abcnews.go.com/Health/anxiety-head-gut/story?id=20229136

    Maybe this has since been discussed here or on SGU. But this story went further, saying “A study published in Nutritional Neuroscience from The Great Plains Laboratory, has shown that HPHPA levels are much higher in the urine of autistic children.” They also cover the same case study and “miracle cure”, and the same Dr. James Greenblatt saying “”I don’t know why this test isn’t done on every psychiatric patient… I question that every day.”

    As the father of an autistic boy, such a strongly worded statement genuinely interested me. What about this study; is there anything to it? Who is James Greenblatt, who keeps popping up in these stories? What is the Great Plains Laboratory (GPL form here on)? Being a PhD in zoology and a science writer/editor, I’d never heard of this facility. Is it akin to the Cleveland Clinic, the Mayo… what is it? So I did a little digging.

    The key study discussed here, Shaw 2010, is by William Shaw, PhD, of the GPL(http://www.greatplainslaboratory.com/home/eng/home.asp). It concludes that HPHPA levels are markedly higher in autistic children, and treatment with antifungals or other gut flora modifications can greatly benefit these children. The methods and statistics are somewhat dubious, and have never been repeated as far as I can tell. The paper comes off more like an opinion piece than a piece of science. But it certainly isn’t the first time that a journal has published an article with shaky results.

    As for GPL? Well, they’re a testing lab that conduct their own non-standard tests to detect a variety of things that, according to them, are related to many difficult-to-treat illnesses such as fibromyalgia, chronic fatigue syndrome, autism, etc. Shaw not only is based out of GPL, he is its founder and Director. I’ve read that certain doctors (I assume Dr. Greenblatt among them) send their labs to GPL, saying only GPL can detect what they’re looking for.

    Of course, it’s a problem that such minimal (possibly questionable) research is being used to drive treatment of autistic children. But a bigger problem with Drs. Shaw and Greenblatt is they’re behind a cottage industry promoting unproven treatments on a large scale, and involving serious conflicts of interest. Dr. Shaw is not only founder of GPL, but is also the founder and head of New Beginnings Nutritionals, a company that sells you the supplements that will cure all these ills! According to them. (http://www.nbnus.com/about-us.html)

    A little more digging told me that James Greenblatt, is a Defeat Autism Now! (DAN!) provider (http://wholehealthamerica.com/designs/bp.php?idnum=97&zt=article&articleid=30463&categoryid=43&display=article)… as I’m sure you know, DAN! promotes chelation and other harmful, unproven therapies for autism, and still promotes the idea that vaccines cause autism (http://en.wikipedia.org/wiki/Autism_Research_Institute). But worse, in light of his promotion of probiotics for mental health, Dr. Greenblatt is connected with GPL He not only promotes their ideas on his website (http://www.integrativepsychmd.com/freewebinar2.html), but he “serves as Medical Consultant for Mental Heath Disorders for New Beginnings Nutritionals” (http://www.greatplainslaboratory.com/home/eng/manual/Introduction_Zeebra_Formulations.pdf).

    Dr. James Greenblatt and Dr. William Shaw run a racket. And it seems like they’ve got a pretty good PR machine in place, and ABC News (among others) are the last people who are going to question it.

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