Are the bacteria/parasites in your gut affecting your thinking?

by witzvo3 min read9th Jun 201240 comments

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There is a variety of science going on, mostly in mice, about how intestinal microbiota (bacteria/parasites/fungi?) can affect behavior, emotion, and mental development (Review paper: The micro-biome gut-brain axis, 2011. Review paper 2009). Does any of it have relevance to those of us who'd like to be better rationalists? I'm just beginning to look into this and I'm not a biologist, so I could use help. I'll reference some interesting papers here and give interesting excerpts.

To start off with something easy to read, here is an excerpt from a press release for this 2011 paper about effects on mice:

Working with healthy adult mice, the researchers showed that disrupting the normal bacterial content of the gut with antibiotics produced changes in behaviour; the mice became less cautious or anxious. This change was accompanied by an increase in brain derived neurotrophic factor (BDNF), which has been linked, to depression and anxiety.

When oral antibiotics were discontinued, bacteria in the gut returned to normal.

"This was accompanied by restoration of normal behaviour and brain chemistry," Collins said.

To confirm that bacteria can influence behaviour, the researchers colonized germ-free mice with bacteria taken from mice with a different behavioural pattern. They found that when germ-free mice with a genetic background associated with passive behaviour were colonized with bacteria from mice with higher exploratory behaviour, they became more active and daring. Similarly, normally active mice became more passive after receiving bacteria from mice whose genetic background is associated with passive behaviour.

While previous research has focused on the role bacteria play in brain development early in life, Collins said this latest research indicates that while many factors determine behaviour, the nature and stability of bacteria in the gut appear to influence behaviour and any disruption, from antibiotics or infection, might produce changes in behaviour.

The writing in the abstract is a lot more abstruse, but perhaps substantially more accurate too. I'd be happy to know if anyone can translate it more accurately than this press release. (E.g. they didn't just transfer bacteria)

Naturally, the experimenters are doing things to the mice they'd never get away with on people, and so less is known about the relevance to humans. For example, normal humans may already have reasonably healthy bacteria. College students, for example, did not have a significant reduction in exam-related anxiety by consuming yogurt rather than placebo [citation]. Nor did healthy 1 to 3 year olds miss less school because by consuming a Gerber product with yogurt [citation].

However, humans with chronic fatigue syndrome who consumed a potent pro-biotic had reduced anxiety (but not reduced depression): [citation]

Chronic fatigue syndrome (CFS) is complex illness of unknown etiology. Among the broad range of symptoms, many patients report disturbances in the emotional realm, the most frequent of which is anxiety. Research shows that patients with CFS and other so-called functional somatic disorders have alterations in the intestinal microbial flora. Emerging studies have suggested that pathogenic and non-pathogenic gut bacteria might influence mood-related symptoms and even behavior in animals and humans. In this pilot study, 39 CFS patients were randomized to receive either 24 billion colony forming units of Lactobacillus casei strain Shirota (LcS) or a placebo daily for two months. Patients provided stool samples and completed the Beck Depression and Beck Anxiety Inventories before and after the intervention. We found a significant rise in both Lactobacillus and Bifidobacteria in those taking the LcS, and there was also a` significant decrease in anxiety symptoms among those taking the probiotic vs controls (p = 0.01). These results lend further support to the presence of a gut-brain interface, one that may be mediated by microbes that reside or pass through the intestinal tract.

Interestingly, the ongoing clinical trials don't seem to be following up on this line of treatment, instead focusing mainly on drugs or alternative therapy. The jury seems to still be out in inflammatory bowel disease.

Late-onset autism, is associated with bacterial irregularities [citation] and can respond to oral vancomycin (an antibiotic) [citation].

Going back to mice, these findings indicate that the bacteria that are present during development have a lasting effect:

Hejitz et.al.: Normal gut microbiota modulates brain development and behavior, 2011.

Here, we report that colonization by gut microbiota impacts mammalian brain development and subsequent adult behavior. Using measures of motor activity and anxiety-like behavior, we demonstrate that germ free (GF) mice display increased motor activity and reduced anxiety, compared with specific pathogen free (SPF) mice with a normal gut microbiota. ... Hence, our results suggest that the microbial colonization process initiates signaling mechanisms that affect neuronal circuits involved in motor control and anxiety behavior.

They found that if they "conventionalized" the germ free mice early enough (i.e. if they infected them with the usual bacteria) that they'd be pretty much normal. However, if they tried to do this on adults, it was too late, so the absence of the bacteria during development had an enduring effect on behavior.

Encouraged by the observation that early colonization of GF mice could normalize several behavioral patterns of GF mice, we explored whether there is a sensitive/critical period for the effects of the normal gut microbiota on behavior. We therefore conventionalized adult GF mice and studied their behavior in open field test as described above. Notably, conventionalization of adult mice failed to normalize the behavior of GF mice (Fig. 1F and Fig. S4).

Conversely, if the animal is subjected to stress, this can change the composition of microbiota. [citation]

Although many people are aware of the communication that occurs between the gastrointestinal (GI) tract and the central nervous system, fewer know about the ability of the central nervous system to influence the microbiota or of the microbiota's influence on the brain and behavior. Within the GI tract, the microbiota have a mutually beneficial relationship with their host that maintains normal mucosal immune function, epithelial barrier integrity, motility, and nutrient absorption. Disruption of this relationship alters GI function and disease susceptibility. Animal studies suggest that perturbations of behavior, such as stress, can change the composition of the microbiota; these changes are associated with increased vulnerability to inflammatory stimuli in the GI tract. The mechanisms that underlie these alterations are likely to involve stress-induced changes in GI physiology that alter the habitat of enteric bacteria. Furthermore, experimental perturbation of the microbiota can alter behavior, and the behavior of germ-free mice differs from that of colonized mice. Gaining a better understanding of the relationship between behavior and the microbiota could provide insight into the pathogenesis of functional and inflammatory bowel disorders.

Whew. That's a lot of material. And there's still so much more to find out. Let me know what you find, or what you think the next experiment should be.

DISCLAIMER: I am not an expert in medicine. Nothing here should be construed as medical advice. See your doctor.

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I think it's a cute demonstration of materialism - "Behold! Not only is your mind a physical brain, but it's affected by your gut bacteria!" - but I don't see any further ramifications.

For the long haul, there might be useful self-modification by changing one's gut bacteria.

I was wondering whether there are any undiscovered body systems, and something for managing one's microflora seems like a good candidate.

For the long haul, there might be useful self-modification by changing one's gut bacteria.

Agree. There could be a whole new continent of health improvements achievable by managing the body's bacterial ecosystem in the way a professional gardener manages a botanical garden. It might be possible to breed or genetically engineer especially helpful bacteria. We can't really improve or re-engineer a living person's DNA, but we can improve the DNA of a person's bacterial symbionts.

There could be a whole new continent of health improvements achievable by managing the body's bacterial ecosystem in the way a professional gardener manages a botanical garden.

Is eating an effective way to do that? In the world's cultures there's a wide variety of pro-biotic fermented foods. Do these exist merely because people like the taste? Surely they partly exist as a coping strategy for rotten food, but is that all? I doubt it. In some cultures they're eaten regularly. Let's list some:

  • yogurt / cheese / cottage cheese / sour cream / kefir / etc.
  • sauerkraut / kim chee / pickled vegetables
  • fermented tofu (e.g. stinky tofu)
  • fermented rice
  • kombucha

Diet generally can dramatically affect which bacteria thrive in the gut (e.g. I recall evidence about sugar consumption, but can't find it). [I don't list bread or wine because as far as I know the agents are mostly dead before we eat them. For that matter, I'm not sure how much is alive in commercially available cheese.][Hygiene practices vary substantially too which probably has an important effect.]

One day we will raise the sanity waterline by selling Rationality Yogurt.

This is already sold. It's called humility, but you'll have to import it if you live in the US.

I know humble people outside of US, who humbly visit their church, humbly read their horoscope, or humbly participate in their favorite political movement.

One of Seth Robert's obsessions is with fermented food; his links and posts might be interesting: http://blog.sethroberts.net/category/fermented-food/

It's not quite probiotic, but the bacteria in sourdough seriously reduce the negative effects of wheat gluten; apparently, bread fermentation was widespread across wheat-eating cultures.

You're right, but note that most store-bought sourdough breads are barely sourdough at all; they're mostly just flavored but don't undergo the traditional fermentation process which takes too long for bread corporations more interested in moving stock. Roman legions actually survived largely off of long-fermented sourdough bread.

Cheese is one of the very few commercial foods you'll be able to find live (fermentation) bacteria living in, but even then many cheeses won't because the producers save expense by pasteurizing instead of more closely monitoring cheeses to make sure they don't develop molds.

But, there are a few companies who do sell high-quality raw fermented foods, like Real Pickles up here in New England. You'll be able to find healthy bacteria on organic farm-bought produce as well; sauerkraut can be made easily by putting some sliced cabbage in a jar with salt, pounding it down, topping off the jar with water, and capping it for a week.

What can we do to get some more Cultural diversity into this list of cultured food?

  • Burmese: Tea Leaf Salad

Some people can't digest fructose or lactose, but their gut flora can. The gut flora create gas as a byproduct and certain strains grow because of the extra food for them. This is why lactose intolerant people get bloated and gassy when they eat dairy.

[-][anonymous]9y 2

I had I teacher in microbiology that envisioned a world were people would go on regular gut-flora checkups.

Your italicization practices puzzle me.

[-][anonymous]9y 0

Do you mean in general? I tend to overuse it, cause I think it has nice look to it - bad habit a guess, but since I was introducing a new term (albeit rather useless one) I thought it was appropriate.

I liked it. It emphasized the surprising part of the sentence.

We can't really improve or re-engineer a living person's DNA

yet! http://en.wikipedia.org/wiki/Gene_therapy

If I understand botanical gardens, they're basically for display and not expected to especially take care of themselves. I think it would be more like balancing a salt water aquarium, but much harder.

[-][anonymous]9y 2

Mass wild and unfounded speculation about the cultural implications of the psychological changes brought about by mass exposure to antibiotics in the mid 20th century.

My reactionary thought inducing gut-dwelling worm is all giddy about the possibilities.

Very funny {both meanings}. You're talking about Blindspots, by the way. See also Chomsky on concision.

Interesting topic. There is such a procedure as a "fecal transplant" wherein fecal matter is taken from one person and put into another. To me this seems extreme and a little disgusting, but for people with severe illnesses (typically autoimmune or gut-related, as far as I know), sometimes drastic measures are worth trying. I have no idea if there is any material about this in the scientific literature, but at least to me, given what we are learning about the effects of the body's microbiota, it seems plausible. Who knows, maybe in X years geniuses will be auctioning off fecal transplants to those who want some of their brainpower.

From what I have seen, the effects of less extreme measures like eating Yogurt or taking pro-biotic supplements are quite modest.

Edit:

Found a post that discusses some of the findings in the medical literature related to fecal transplants. No links, unfortunately:

Fecal Transplants

Edit:

Apparently there is actually quite a bit of material on this in the medical literature. It dates back to 1958 and has been used in racehorses for years. Wired article: Fecal transplants work and Wikipedia page.

Ultrasocial naked mole rats) eat each other's poop. Coprophagia it's called.

I've heard anecdotes about the effectiveness of hookworm infection for people with severe auto-immune issues. The only RCT data I've seen is from some brave Canadians on patients with asthma. I'll mention the study limitations before mentioning the results so that we can decide in advance how big an update to make. 1) the patients received 10 hookworm larvae under a bandage on their arm, not a fecal transplant, but this had been sufficient to establish infection in previous volunteers 2) there were 16 participants in each arm which "powered" the study to detect a 2x change. Results:

Mean PD20AMP improved in the hookworm group by 1.49 (SD 2.00) DD and in the placebo group by 0.98 (4.02) DD, but the mean difference between these changes was not statistically significant [0.51 DD; 95% confidence interval (CI) −1.79 to 2.80; P=0.65, Table 3].

EDIT: Post facto we see that their power calculation was to detect a shift of 1 in PD20AMP with 80% power with the assumption that the standard deviation of this measurement is 1, but actually the standard deviation observed in the pool is about 3.2 (32 patients, 30 degrees of freedom). This suggests the study was underpowered to detect a shift of 1. E.g. the sample size needed to have 80% power to detect a shift of 1 if the population s.d. is 3.2 is 161 patients per arm. (calculated using: "power.t.test(delta=1,sd=3.2,power=0.8)" in R).

[From a Bayesian point of view, the results of the study data themselves are weak supporting evidence (the observed shift was favorable after all). But now I know I'm at risk of cheating mentally, because I was going to update based on the study findings.]

The writing in the abstract is a lot more obtuse,

The word you want is 'abstruse'.

Quite right! Thanks. Fixed.

[-][anonymous]9y 3

There is the peculiar fact that when babies are born they turns their face towards the mothers bottom, that results in (often times) that mother's intestinal flora colonize the baby's intestine.

Interesting. How do you know this? Is it in animals or some human scenario with natural birth? I thought doctors just plop the baby on the mother's chest.

[-][anonymous]9y 1

I study medicine, and during a lecture about intestinal flora my teacher talked about it. The Wikipedia article on vaginal birth also mentions it, though not hypothetical function of the rotation.

As a medical student who has been closely reviewing probiotic research, I would like everyone to know that research is extremely important.

Perhaps it will be the greatest breakthrough in medicine of the 21st century. This angle is one of the primary reasons that the 'calories in=calories out' theory doesn't function as a successful principle for people trying to lose weight and keep it off. I recommend looking into the GAPS diet for anyone suffering auto-immune problems, since auto-immune disorders are all primarily caused by dysregulation of the digestive system.

Some ideas on the yogurt study (also being an opportunity to explain some of the nuances):

  1. there is an incredible breadth of biodiversity in the gut, and yogurt only typically contains one or two strains, in this case it looks like one.

  2. gut bacteria number in the trillions, so a short-term regime of any probiotic food or supplement won't necessarily provide its benefits quickly. A significant amount of the benefit is also delivered in the chelating and detoxifying properties of healthy bacteria, which can over time remove harmful toxins built up in intestinal bile; a significant build-up may take years to fully flush though, and other health problems may still still inhibit it.

  3. other things in the diet will impact bacterial growth just as much as the addition of yogurt. Foods high in sugar could very easily be inhibiting the multiplication of the yogurt's probiotic bacteria (after being ingested) by encouraging the growth of competing bacteria associated with negative health. Food eaten then also becomes the basis for the bacteria's food, so a poor quality diet could sabotage the probiotics.

  4. the quality of the yogurt which the probiotic was added to will impact the growth of bacteria tremendously. The pasteurization process itself makes the yogurt less healthful and can create an environment less conducive to probiotic multiplication.

  5. no distinction is made whether the stress can be considered 'justified' or not; it would be undesireable to be less stressful in a situation where stress is justified and helpful. The study also seems not to account for variance in difficulty of course load, since students may have signed up for classes with intuitive knowledge of the additional stress received through their usual gut bacteria.

  6. there are also a variety of standard practices in preventing contamination, which I assume the group carried out

We have around 500 species of bacteria living in our guts. Yogurt uses only 2 or 3 species of bacteria. So it's not surprising that eating yogurt didn't change various aspects of behavior. If those behaviors are affected by gut bacteria at all, it's unlikely to be the particular strains found in yogurt.

We have around 500 species of bacteria living in our guts. Yogurt uses only 2 or 3 species of bacteria. So it's not surprising that eating yogurt didn't change various aspects of behavior.

Great point. We have, as far as I know, little direct information about how effective the fecal transplants mentioned above really could be (at least in humans) in situations that aren't last resort.

I attribute this ignorance to the (important and reasonable but perhaps exaggerated) desire to protect us from risks of unknown treatments. The unfortunate consequences are ignorance and an interest in "alternative therapies" (which we could generously characterize overall as experimentation by non-professionals without proper institutional support).

Edit: I think I see another discussion post forming here in my head, but I'm getting a bit carried away.

The jury seems to still be out in infectious bowel disease.

The link is about inflammatory bowel diseases. These are not infectious.

Thanks. Will fix it.

That our health and body chemistry affects our mental processes, is not unreasonable to expect. More interesting would be if this goes the other way.. do our belief systems and rationality have a profound impact on our body chemistry?

For instance, I wonder if being rational and self-aware drives our digestive system to become clever over time.. consider that we may have a hoard of gastric juices which our body tries and tests on various kinds of foods, keeps a track of which works better, and adapts accordingly. It may also try to create newer juices and see how they work.. At the extreme end, we would be leading our body to set up a gastrochemistry lab in our guts.

Another example: I hope that studying computer science may lead one's own brain to apply those concepts to optimize one's neural connections in some way.. give us 'speedup', so to say.

More interesting would be if this goes the other way.. do our belief systems and rationality have a profound impact on our body chemistry?

Some of the articles describe the symbiosis as a two-way communication. For example, the article I mention at the end goes on to say:

There are several mechanisms by which stress can alter the bacterial composition of the GI tract, including changes in epithelial cell function and mucus secretion as well as changes in GI motility. 41,43,44 As described, release of norepinephrine into the GI tract during stress might preferentially stimulate the growth of specific strains of bacteria as well as their ability to adhere to the mucosa. 32–34

[-][anonymous]6y 0

Atovaquone treats toxoplasmocosis, which, together with genetic susceptability and other effect modifiers, may be one cause of schizophrenia. What existing data might exist to allow me to test this hypothesisi? Quick google searches suggests Atovaquone at the very least, tends not to be associated with anxiety or psychosis as side effects which for one is a good sign. Note, most schizophrenics aren't infected with toxo. they are just infected at a higher rate so it could explain a subset.

Here's a new report that suggets that children who are exposed to bacteria transmitted by dogs may be protected children from childhood asthma, because they bring about changes in our immune system which protect from a virus or because they change our gut flora. They carried out experiments on mice:

The researchers fed mice house dust from homes with dogs. They then exposed these mice to RSV and found that the mice did not show symptoms of infection -- airway inflammation and increased mucus production. They also compared the intestinal bacteria of dust-fed mice to mice that hadn't been fed dust and found differences in the types of bacteria living in the GI tract. These differences were seen whether or not the non-dust fed mice had been exposed to RSV.

I predict in the future psychiatrists will be more interested in our gut health than the brain directly... most mental illness seems to co-occur with unusual patterns of gut dysbiosis and loss of gut barrier function. In some cases the direction of cause and effect isn't clear, since rat studies have shown brain damage can result in gut dysfunction. This might even result in a positive feedback loop where mental dysfunction and gut dysfunction promote each other simultaneously. If so, such conditions would resist treatment, but may be permanently cured once treatment is successful and the feedback loop is stopped.

Exactly how to fix these issues is not clear, and is going to be more complicated than just taking probiotics or even transferring in desired bacteria directly (fecal transplants). In particular pre-biotics (substrate foods that promote growth of preferred bacteria), and removing molecules that often interfere with gut function (lactose, gluten, etc.) are likely useful as well.