Saturday, January 28, 2012

More Evidence for a Gut-Brain Connection

Someone (Stephen B) emailed me via Google +, which I didn't know was possible, mostly because I have yet to bother to figure out anything about Google +, mostly because my reading pile is dangerously high and Google+ wasn't very iPad friendly.   If I'm going to figure out any new complex system of communication with circles, it had better be with my feet warm and snuggly under the covers, thus iPad friendly.  Now you know my opinion, so go work on that, Google.

Neon Trees.  Everybody Talks (right click to open in new tab).

The abstract of the paper Stephan sent me seemed mighty intriguing indeed (pardon the font hiccup here but I am too lazy to type it out rather than cut-n-paste and Blogger is dreadful about editing such things.  My, I am certainly opinionated today!).  Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve

I know that title might not make everyone's heart go pitter patter immediately, but it is actually Evolutionary Psychiatry exciting. As I noted in a couple of previous blog posts, it is clear that (in mice, anyway) the wee beasties of the microflora in the gut (comprising about 90% of the cells in our bodies) have something to say about behavior and moods.  In addition, behavior and mood can affect the population of the gut flora.  But how the communication proceeds is a bit mysterious.  Hopefully this paper will shed some light.

First off, a little bit about GABA. It is the major inhibitory neurotransmitter in the central nervous system (glutamate being the major excitatory neurotransmitter). GABA is a nice glass of wine in front of the fire.   GABA is restful sleep.  GABA is tranquility and yoga.  Not surprisingly, GABA plays a major role in conditions such as anxiety disorders and irritable bowel syndrome.

Now let's introduce Lactobacillus rhamnosus.  These little bacteria can modulate the immune system via manipulation of TNF-alpha and IL-8, and can change T cell production.  In addition, in rodents, it reduces the autonomic nervous system response to intestinal distention and alters small intestinal motility.  That's a lot of long range action for a wee beastie.

So, for the study, the researchers gave some mice probiotics, and other mice got broth.  Then the mice were tortured in various ways to induce a stress response.  Some of the mice had surgery to sever the vagus nerve (which is the major communication highway between the gut and the brain).  And mice ultimately made the ultimate sacrifice to have GABA levels and mRNA levels measured in the brain.

The results:  mice who go the probiotics were, in general, more chilled out than the control mice.  The probiotic mice had lower levels of corticosteroid release in response to stress.  Steroids are something the body pumps out as an emergency reaction to stress, and while in the immediate timeframe they can save your life (grandma lifting the car off the toddler, for example), in the long run, chronically elevated stress hormones like steroids can lead to depression, anxiety, heart disease, you name it.

Mice who had their vagus nerves severed did not differ from the control mice so did not experience the anxiolytic effects of the Lactobacillus probiotic.  This would suggest the communication from the bacteria (via its own neurotransmitters? or via immune modulation in the gut) definitely goes through the vagus nerve on its way to the brain to control behavior.

In addition, when the brains of the little mice were tested, the amounts of mRNA of various types of GABA receptors (reflecting the amount of messages from the genes to create the GABA receptors) were higher in certain key brain areas of certain key subtypes of GABA receptor.

So what does it all mean? Actually, the authors of the study summarize nicely (the "HPA axis" is the connection between the brain and adrenal glands and how corticosteroids are released and regulated, and there is more font hiccuping. Sorry):

Furthermore, in this study we observed that L. rhamnosus administration reduces the stress-induced elevation in corticosterone, suggesting that the impact of the Lactobacillus on the CNS has an important effect at a physiological level. Alterations in the HPA axis have been linked to the development of mood disorders and have been shown to affect the composition of the microbiota in rodents… Moreover, it has been shown that alterations in HPA axis modulation can be reversed by treatment with Lactobacillus and Bifidobacterium. However, caution is needed when extrapolating from single timepoint neuroendocrine studies. Nonetheless, these data clearly indicate that in the bidirectional communication between the brain and the gut, the HPA axis is a key component that can be affected by changes in the enteric microbiota.
So, once again, a common ancestral practice to consume fermented foods rich in probiotics is quite interesting.  There is almost no evidence in humans as yet for psychiatric disorders (the only scientific evidence I'm aware of is discussed in my blog post here).  But all in all the data and research  looks to be very interesting, and perhaps promising.

12 comments:

  1. I love your writing style...fonts and all. Going to take my probiotics for the afternoon right now.

    Wendy Schwartz
    The Paleo Cure
    http://paleocure.com

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  2. I find this interesting (even though I don't necessarily grasp all the science of it). I started eating a Primal diet in Sept., eliminating all grains and processed foods from my diet, and also increasing my consumption of fermented foods and probiotics. Among many other health benefits, my depression has lessened dramatically, to the point where I'm about to go off medication completely. So I have no problem believing that there's a direct link between gut health and mood!

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  3. Dr. Deans
    My experience with lo-carb, unremarkable to many folks out there, lost 40 pounds, after a couple of years, with no change in diet gained 15 back. Finally with the ADF fasting version of IF, I am starting to see the scale backtracking, in only a week so far; five pounds worth.
    In my amazement, as I have tried almost everything to get the scales to budge in a negative direction; your gut-brain hypothesis has me wondering. Is it possible in the gut-brain communication there is more going on than quantity of type of food; for example, could the tummy undergo a form of confidence training that by withholding food for over 24 hour period and then re-feeding? Once the organism learns, perhaps by a mind connection not to panic and hoard every morsel of food and relax as food is not scarce and will be available in time.

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  4. Candace Pert recounts some very interesting findings in Molecules of Emotions which clearly show the concentrations of various neurotransmitters throughout the body, not just in the brain, which lead her to think in terms of a gut-brain connection, amongst others. Her further thought-experiments began to blend with what Eastern philosophies have long acknowledged in energy centres and meridians and energy networks.

    And, having undergone 4 months of traditional Chinese medicine with 5 element acupuncture I can certainly see, understand and believe there is a connection, in fact TCM is all about the total connectedness of systems and even go as far as to say that the way in which we prepare and eat food (at an emotional level) has an effect on the energetic systems of the body.

    Me thinks that Western empirical science might just be beginning to catch up with 1,000s of years of Eastern knowledge.

    In many ways many diverse paths are beginning to meet as the same destination, and when that happens I do feel we are beginning to reveal a fundamental truth.

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  5. Dr. Deans, ever since your GABA post mentioning yoga and yoghurt, I have made sure to eat my homemade yoghurt regularly, and do yoga daily. Thanks very much for underlining this point with more evidence. I do notice that they improve how I feel.

    I make the yoghurt from heavy whipping cream mixed with half-and-half, and incubate it for twenty-fours to reduce lactose.

    All the best to you!

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  6. Nice song and thank you for the write up. Bacteria are becoming more and more friendly everyday.

    Providing my family with homemade raw kefir smoothies makes much more sense from a preventive perspective. I just got my starter for kumbucha and think it will also contribute nicely.

    This subject is particularly relevant to me since my boy's system is sensitive to GM wheat and other refined processed foods. He ate an ice cream cone two days ago and the effects are still impacting him. He is now paleo by necessity . . . at 6 years old. I can rest in the fact that I caught this a year ago and most of his problems have been resolved. I wonder what awaited him if he continued with a SAD.

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    1. just a note..many people mistakenly believe that wheat is a GMO (genetically modified organism). This is not so. It is hybridized which is much different than implanting a gene from a totally unrelated species such as a bacterium. GMO in agriculture/food typically refers to the insertion of a foreigh gene which is not found within the plant species itself. Hybridization is a cross within a species or similar species. dogs(mutts)/wolf-dogs.

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  7. Probiotics help my kids’ issues (psych and physical) about 10% ; Paleo helps 80%; I am working on the last 10%.
    An interesting thing: yogurt does NOT help while Kefir and Sourkraut DO…but only for about a month... when I have to stop and wait and start again. (if any one is interested in details, I am happy to post them). I am currently doing an experiment with probiotic supplements to figure it out.
    I have a question for Dr. Deans: what biochemical pathway would be implemented in ‘transient tic disorder’ (my 8yo diagnosed here in the UK NHS: wait for a year, if still present, then she gets a referral)… the funny thing is after a non-paleo Christmas her tics got incredibly worse and then better now eating paleo again. Could it be a dopa/seratonin balance thing? Or anything else? Thanks.

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  8. There is some evidence that infections (particularly strep) and inflammation worsen tics (see the literature on PANDAs). It might be that a paleo-diet reduces the inflammatory response to the PANDAs and reduces tics. That is merely speculation, however.

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  9. Good evening Emily,
    is an Italian woman, I'm looking for some personal use studies done to confirm my theories about the link intestine and mood. I found them here!
    I am not a doctor, but for some years I'm looking very closely and I'm sure there is relevance to what I eat and then parked in my gut, with a lowering of mood and anxiety. Surely I knew that legumes are not good for my mood.
    Doctors are not yet able, today, to understand these subtle links ..... Unfortunately there is not spoken and the mesh material is scarce. And I have difficulty with English!
    Thank you for what I have read here, unfortunately I could not understand everything because of the language.
    Stefania

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  10. I just came back from a lecture by Dr. Paul H. Patterson (CalTech) entitled "Brain immune gut connections in autism, schizophrenia and depression." His current working hypothesis is infection in the mother during pregnancy is one cause of autism, schizophrenia and mood disorders; in which trimester the infection occurs gives rise to different symptoms in the offspring. He also noted a significant co-morbidity of these disorders in humans with GI disorders. He was able to reverse some of the rodent offsprings' symptoms (anxiety, stereotypic behaviors) using B. fragilis. B. fragilis appears to help the "leaky gut" syndrome. All his work was with rats and mice, but he has done some collaborative work in monkeys also. I believe he has written a book with the same title as the lecture. Very interesting.

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  11. I think there is a bigger picture than just the gut. I do not have much of a pituitary gland left. My doctor has me off of all medications except Levothyroxine. Which I agreed with because drugs mask what the body is doing and saying. I have been trying to control a rollercoaster ride of diverse medical and phsychological responses in my body through nutrition, probiotics, and bio feedback. I keep a journal to try to log the my body activity, food, temperature, etc. I am looking for patterns and correlations to link the symptom to the deficiancy, so that I can better respond, and bring my body back to a more normal state. Depression was hard because I do recognize when the brain is irrational in response, and in my body it swings alot. I have learned to just turn off the response as soon as I see it, but sometimes it is determined to fight, so I will use this information and double my pro-biotic. Hahaha I am my own lab mouse for science. I really want others after me to have help with Hypopituitarism, Hypothyroidism, and the many problems this all causes in the entire body. I have learned though, it is not all one thing, it is I think based on the study of my own body, a very complex combination, with many redundant ways to get the hormones, I call them chemicals, and processes done. Even things we think cause problems may actually be the bodies way of trying to repair or make a seperate pathway. Some chemicals I have in "normal" amounts I should not have. Through my research, I am finding many different scientific research that gives another tiny part. I think it is going to be a very long time before we actually give up the old ways and realize we really do not know much at all, but we can if we keep searching. Thanks so much for the blog post, it is just one small part of a really bigger picture, but so necessary to aid in ways to treat many diseases and health issues.

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