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.