Gut Feeling
April 14, 2014 9:27 PM   Subscribe

Being a T1 diabetic, I can definitely tell you that having your digestive ecology perturbed by blood sugar fluctuations has a strong and varied effect on the mind.
posted by BrotherCaine at 9:47 PM on April 14, 2014 [5 favorites]

The premise is starting to look plausible, but the article set off my woo-dar in a hurry.
posted by wotsac at 9:59 PM on April 14, 2014 [6 favorites]

Fascinating, but shouldn't there be profound psychological changes from taking a round of antibiotics? Or more lingering effects from a bout of heavy drinking?
posted by three blind mice at 10:00 PM on April 14, 2014 [2 favorites]

Serotonin and its role in colonic function and in gastrointestinal disorders.
Serotonin (5-HT) is most commonly thought of as a neurotransmitter in the central nervous system. However, the predominant site of serotonin synthesis, storage, and release is the enterochromaffin cells of the intestinal mucosa.
Gastrointentinal Neurotransmitters
Think Twice: How the Gut's "Second Brain" Influences Mood and Well-Being
posted by the man of twists and turns at 10:00 PM on April 14, 2014 [4 favorites]

Interesting. I've used probiotics to tend to GI issues related to my medications for years. Anecdote ain't data, but I do feel better with them than without. I've always figured it to be a result of not dealing with GI distress. It's unpleasant to be in pain.

I do appreciate Bienenstock's caution to not get too jumped up just yet, but knowing the woo industry, probiotics are about to be this year's cure-all. They will join such discarded luminaries as goji berries, blueberries, and acai. Which is a shame, because they are beneficial to many. They're simply not a miracle cure.
posted by MissySedai at 10:19 PM on April 14, 2014 [1 favorite]

I dare say that having blood sugar fluctuations is going to have a strong and varied effect on the mind even if it doesn't perturb your digestive flora.
posted by Kid Charlemagne at 10:31 PM on April 14, 2014 [2 favorites]

> Fascinating, but shouldn't there be profound psychological changes from taking a round of antibiotics? Or more lingering effects from a bout of heavy drinking?

IANAD, but I'd guess that those aren't necessarily big factors because of their short term. They are talking about more long-term effects.
posted by zardoz at 11:44 PM on April 14, 2014 [1 favorite]

The future of psychiatry may be inside your stomach.

Ah, it's the random phrase generation game! I love this one, let's spin the wheel:

The alternative to urban sprawl may be at the bottom of the sea!
The secret of Thanksgiving may be the planet Mars!
The implications of voting Independent may be too horrible to contemplate!
The contents of my left ear may be the doom of us all!
posted by JHarris at 11:56 PM on April 14, 2014 [9 favorites]

Here is a review that covers these ideas a lot better,
The adoptive transfer of behavioral phenotype via the intestinal microbiota: experimental evidence and clinical implications
Intestinal commensal bacteria or their products may be used to treat CNS disorders.
There is growing interest in the ability of the intestinal microbiome to influence host function within and beyond the gastrointestinal tract. Here we review evidence of microbiome–brain interactions in mice and focus on the ability to transfer behavioral traits between mouse strains using fecal microbiota transplantation (FMT). Transplantation alters brain chemistry and behavior in recipient ex-germ free mice, raising the possibility of using FMT for disorders of the central nervous system, and prompting caution in the selection of FMT donors for conditions that may include refractory Clostridium difficile infection, diabetes and inflammatory bowel disease in humans.
•Behavioral phenotype can be transferred via the intestinal microbiota in mice.
•Changes in behavior in recipient mice are accompanied by changes in brain chemistry.
•Investigation of the intestinal microbiome in central nervous system (CNS) disorders is warranted.
•Donor screening for fecal transplants should exclude CNS and psychiatric illness.
If you would like access to it or any of the other linked research, please feel free to memail me with the desired paper, an email address I can send a PDF to, and a promise not to distribute that PDF further. If you then came back to the thread with questions or things you learned that would make me embarrassingly happy, but no pressure.

I hope the subject will be a lot more clear over the next year or two, looking through the authors names in the references of this review it seems like a lot of people who used to be doing probiotics when that was more exciting are now studying this, and their papers have been publishing pretty astonishingly well, so it looks like we can look forward to more work being done. Behavioral/neurological microbiology was beginning to be a thing back in the '90s before it kind of fizzled out with a lack of results that could be described as both exciting and solid, at least beyond a few clearly demonstrated but very narrow conclusions - like how you can treat some brain disorders in mice with antibiotics in ways that don't make sense otherwise. If they get enough money to do it, maybe they'll find some interesting things using the modern sequencing techniques that have pretty clearly demonstrated how linked microbiota is to obesity in the last couple of years, as well as Chrons disease just last month, the radical clarity of which I think the paper sadly undersells; I would be surprised if the Human Microbiota Project isn't currently throwing their sequencing resources at them with its broad mandate.

The germ-free and SPF mice results that the article discusses aren't so convincing to me as Germ-free, and even SPF mice, are pretty sick critters - so showing them acting weird because of general microbiota related ill-health could for most of those papers just as easily be explained as a trivial finding. Microbiota are intricately involved in mammalian metabolism, almost like another organ, and so saying that starving critters act weird is maybe not so novel even if it does help to establish the case for everything else. The various papers showing that you can turn crafty, cautious, misanthropic, and anxious Balb/c mice into dumb, trusting, and cuddly NIH Swiss mice and vice versa by switching out their flora, however, make a pretty strong case that there might be something to this field that we didn't catch in the '90s.

The various human results that the article talks about are also a lot less convincing with the methodological problems the authors are careful to either explicitly or obliquely refer to. Overall though, I think those authors make a pretty decent case for the only two conclusions they actually make, that some serious caution related to potential neurological and psychological conditions in fecal donors is warranted because we might just be playing with fire (that is, in addition to poop), and that someone should probably put together some better designed studies seeing how fucking with the microbiota of people with neurological and psychological disorders affects things.

There is a lot of crazy and woo around all of this, like how the modern anti-vaxx movement is built around Wakefield's clearly fraudulent connection between the gut and the MMR vaccine, as well as various diets that all lack clear evidence. However, the basic idea that some neurological disorders can be positively or negatively affected by the microbial composition of the gut, and thus diet, is all more than essentially plausible - even if there is no clear evidence pointing to any particular neurological disorder being affected this way, or microbial composition that can have such an effect, or diet that can cause that composition. A solidly convincing and useful case should require a clear demonstration of at least the first two, which modern sequencing should be able to either demonstrate or not.

The effects of something like that being found are kind of fun to think about though, psychiatric facilities would need to get a lot more particular about poop, the ethics and logistics of fecal transplants for both C. difficile problems and psychiatric/neurological disorders would get really weird really fast, and "splashback" would turn into a simultaneously dead serious, disorienting, and hilarious epidemiological concern.
posted by Blasdelb at 11:58 PM on April 14, 2014 [38 favorites]

Not as modern woo as it sounds. Malabsorption of certain key nutrients (through....the digestive tract) have been known to result in organic (and often dramatically reversible, except in the case of something like Wernicke-Korsakoff syndrome--a result of thiamine deficiency) psychiatric illness for a very long time now.

Some much less woo-vibe (but still layman friendly) articles by medical doctors:

Here's a woman whose frank psychosis was resolved in ten days with B12.

Here's a case study involving a Turkish teenager thought to have been descending into major mental illness, which resolved after two weeks of B12 injections.

Here's a broader look at the intersection between nutritional deficits and psychiatric manifestations.

The obvious disclaimer is that these kinds of cases are not common--the feeling of "woo" I think comes from the sad reality that, in desperation or in shame, people who have genuine psychogenic or inherited mental illness may grasp at this as a cure-all for their own problems, or an excuse to not seek psychiatric help or to discontinue medications.

But everyone who presents with "treatment resistant mental illness" should be getting a full workup (blood work, neurology exam) if clinical signs point to a possible malabsorption issue (which itself isn't always the final word; neuropsychiatric symptoms can precede signs of anemia in bloodwork--but there are other next-level measures of deficiency that can be tested, and the supplementation itself is seen as diagnostic if it works). But right now that itself is not common, unless you can pay to be taken seriously as a medical patient with a really great diagnostician, or diagnostic team. A Mayo Clinic patient with pernicious anemia or h pylori manifesting as neuropsychiatric illness that can be returned to health is could just have as easily have been a community health care clinic patient with a permanent psychiatric disability to be managed imperfectly with psychotropic medications and counseling--unless this is more widely on the radar screen as something to check for. Ironically, those with a psychiatric diagnosis are least likely to be taken seriously and evaluated thoroughly as medical patients.
posted by blue suede stockings at 12:08 AM on April 15, 2014 [15 favorites]

In a study led by Cryan, anxious mice dosed with the probiotic bacterium Lactobacillus rhamnosus (JB-1) showed lower levels of anxiety

Imagine that we as a species have established protocol for the diagnosis of anxiety in rodents.

OnT: I'm seriously considering a probiotic diet. Any recommendations?
posted by Foci for Analysis at 12:16 AM on April 15, 2014 [1 favorite]

"OnT: I'm seriously considering a probiotic diet. Any recommendations?"
This is the NIH education page with references, which is a great introduction to the current evidence based understanding of what probiotics can be reasonably expected to do for you.

Also important to keep in mind is that in the last 20+ years of extremely active research, no one has yet to demonstrate that they have a culture of anything that will actually positively affect the health of either healthy or sick volunteers when given live that doesn't also have the exact same effect when given dead. How 'raw' anything is cannot be reasonably expected to have any positive health effects, and depending on how 'natural' and 'legit' something is could certainly be expected to have negative effects. Paradoxically though, even dead many probiotic cultures have been show to possess statistically significant if small positive effects on either or both healthy and sick volunteers. The most plausible theoretical model for why this is the case posit that probiotic cultures, live and dead, serve as especially effective food for feeding the cultures you already have.

Really, unless you're just overwhelming your microbiota with a complete foreign set (which needs to happen from the other direction to be safe), more or less anything you eat will be sitting ducks for your immune system, which is already adapted to the microbiota you've got, as well as your microbiota, which is already adapted to the stance and idiosyncrasies of the immune system you've got.
posted by Blasdelb at 1:07 AM on April 15, 2014 [5 favorites]

Kid Charlemagne, obviously there are direct effects of depriving the brain of glucose or changing blood chemistry, but it often seems to me that there must be secondary or indirect effects as well because even when I stabilize my sugars it takes at least a few days to feel right afterward.
posted by BrotherCaine at 1:08 AM on April 15, 2014 [1 favorite]

It's not uncommon for depression to manifest as a feeling in the gut.

MissySedai: and resveratrol.
posted by professor plum with a rope at 1:18 AM on April 15, 2014

"Yogurts like Dannon’s Activia have been marketed with much success as a panacea for all of our intestinal ills."
Dannon Agrees to Drop Exaggerated Health Claims for Activia Yogurt and DanActive Dairy Drink
FTC Charges that Evidence Supporting Benefits of Probiotics Falls Short
posted by Blasdelb at 1:45 AM on April 15, 2014 [2 favorites]

Some of you will get a kick out of Mr Heisenbug.
posted by i_am_joe's_spleen at 3:10 AM on April 15, 2014 [1 favorite]

The pros and cons of probiotics (with additional links) according to the UK's... National Health Service
posted by Mister Bijou at 3:11 AM on April 15, 2014

I have recently, over the past few months I would say, been having a regular serving of cottage cheese around lunch hour. I can't take in yogurt as it initiates a gag reflex for some reason or another, so it was a close enough alternative.

I would have to say that, overall, I feel a bit better, and combined with finding the right friends to have, yacking with the parents, and an overall great work environment, a foundation is being laid for a sustained escape from the... I guess you could call it mid-20s rut.

So while the evidence is still being cleared up, it's not just me but a couple of friends of mine that could probably bear witness: proper food intake along with a few carefully selected special foods, whether it be yogurt or cottage cheese or something else, can make a small difference, but enough of one to help bring people out of a murk.
posted by JoeXIII007 at 4:02 AM on April 15, 2014

It's not uncommon for depression to manifest as a feeling in the gut.

But that feeling in your gut might not actually be your gut telling your brain to feel things; it might just be your insular cortex (which among other things is involved with sensation from your guts... and empathy) acting up.
posted by a snickering nuthatch at 6:15 AM on April 15, 2014

I think this one is going to turn out to be really big:
New research presented at a scientific meeting adds to a growing body of evidence that a toxin produced by a common food bug may trigger multiple sclerosis, an inflammatory disease of the central nervous system ...
and will have implications that go far beyond even MS.
posted by jamjam at 7:29 AM on April 15, 2014 [2 favorites]

Our body is an interlinked system of hormones, chemicals, organs, muscles, bones, blood and mind. Its helpful to isolate factors in order to study them, but we can't act like a change in one system won't impact the other system to various degrees. This includes the mental experience.

No one wants to admit that the mind impacts the body or that the body impacts the mind, because it verges into woo territory. Maybe because we want to feel in more control, or less influenced by our own biology. But really, we're just surfing a wave of hormones, gut-flora, and vitamin absorption, neurotransmitters and amino acids.
posted by St. Peepsburg at 8:03 AM on April 15, 2014 [2 favorites]

"New research presented at a scientific meeting adds to a growing body of evidence that a toxin produced by a common food bug may trigger multiple sclerosis, an inflammatory disease of the central nervous system ..."
While googling this will lead you to an explosion of uncritical articles written by journalists who lack the education to interrogate the concept, the paper at the root of it has a lot of really fundamental weaknesses and should never have been published in PLOS, which is where you send things to be read by people with more ink than sense.

The paper shows three primary results that the toxin binds to myelin, like a lot of things do and without being able to do anything describe the interaction, that antibodies against the pathogen are more present in MS patients than healthy individuals, without being able to present an especially convincing statistical argument for the significance of this apparent difference or explain the order of magnitude more MS patients without detectable antibodies, and the one MS patient with an active infection that they found, which doesn't really demonstrate much of anything at all. For this model to even begin to work they would need to come up with some way of explaining the progressive and relapsing nature of MS in the context of it, which would make no sense in the presence of neutralizing antibodies that effectively block the activity of the toxin and an immune response that effectively combats the infection like they found.

This is to say that while this is perhaps a line of inquiry worth funding more work in to see if the authors can find a meaningful interaction between their toxin and myelin, or maybe replicate MS symptoms in an animal model with the toxin, this is really unlikely to be the answer we're all looking for.
posted by Blasdelb at 8:04 AM on April 15, 2014 [5 favorites]

I was just reading this NPR story about an effect in the opposite direction: different nutritional expectations of the same food moderated the release of ghrelin, a hormone implicated in hunger.

This research all seems definitely new so surely the jury's still out on how consistent these effects are, but this is certainly a little mind-boggling. I mean, studying human cognition is complex enough as is without considering organs-that-aren't-the-brain! It would be convenient if the effects of the gut microbiome on cognition (and vice versa) could be distilled to a few hormone signaling channels... but as is ever the story in psychology, surely it won't be that simple.
posted by nicodine at 8:14 AM on April 15, 2014

Blue suede stockings, it's not so much that the fundamental idea seems like pure woo, it's just that this article (and others that I've seen) have reduced making things with a rock solid empirical data and even a tight theoretical explanation sound like pure woo to an art form. For example, the whole myoglobin-hemoglobin-pH thing is knowledge we've had longer than we've had longer than we've had light bulbs, but here I am, living in the future, and getting pretty regular rants that inefficiently vascularized, fast growing and ergo oxygen starved tumors are acidic in nature and, ergo, baking soda cures cancer and medical science is hiding it! (Meanwhile medical science has rolled it's eyes so far back it can see its own cerebellum.)

I just spent about an hour looking for it (and failing) but there was an FPP once upon a time about a guy who had kid who was tragically ADD/ADHD and his work trying to find a diet that would minimize his sons symptoms. IMHO family services should have gotten involved about the time dad decided his son worked basically like a Geiger counter and was obviously allergic to nitrogen. I think the way this article is written (and my cringing is very much about this article, not the science on which it allegedly reports) it's only going to encourage that sort without doing much to inform.
posted by Kid Charlemagne at 11:05 AM on April 15, 2014 [1 favorite]

Radiolab did a great episode on this a while back.
posted by mysticreferee at 12:05 PM on April 15, 2014 [1 favorite]

Somewhat apropos: Hadza Hunter Gatherer Gut Microbiome.
posted by zinon at 12:55 PM on April 15, 2014 [1 favorite]

The most plausible theoretical model for why this is the case posit that probiotic cultures, live and dead, serve as especially effective food for feeding the cultures you already have.

Makes sense to me. Yeast boosting "feeder" solutions for home brewing are pretty much just a concentrated slurry of already-dead yeast cells.
posted by at 6:49 PM on April 15, 2014 [1 favorite]

Fascinating, but shouldn't there be profound psychological changes from taking a round of antibiotics?

Anecdote, but: My brother developed severe social anxiety after taking a round of antibiotics in his early 20s.
posted by spindrifter at 11:11 AM on April 16, 2014

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