While the brain, doubly protected from the outside by our skin and guts first, then our blood brain barrier, may seem far removed from the human microbiome, there is growing evidence that the trillions of beasties in our guts could communicate with our brains, and that some psychopathology could result from disturbances in the gut microbiome.

Earlier this year, another mouse paper hit the press regarding behavior and consuming probiotics: 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. In mice, anyway, it has been demonstrated that the wee beasties of the microflora have something to say about behavior and moods, and our behavior and moods can also affect the population of the gut flora (click some of the links above for more details). 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 (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 disorders and irritable bowel syndrome.

Now let's introduce Lactobacillus rhamnosus. These little probiotic bacteria can modulate the immune system via manipulation of TNF-alpha and IL-8 (well known cytokines, or chemical signals produced by the immune system and associated with inflammation), and can change immune cell function. In addition, in rodents, the probiotics reduce the autonomic nervous system response to intestinal distention and alter 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 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 got 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 like steroids can lead to , anxiety, heart disease, you name it.

Mice who had their vagus nerves severed did not differ from the control mice in their behavior, so they did not experience the anxiety-killing 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 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 to create the GABA receptors) were higher in certain key brain areas of certain key subtypes of GABA receptor. Meaning mice who had the probiotics made more anxiety-reducing receptors in the brain. Interesting, no?

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):

"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 disorders (the only scientific evidence I'm aware of is discussed in my blog article here). But all in all the data and research looks to be very interesting, and perhaps promising. While some critics felt the Human Microbiome Project might be an enormous waste of money, I feel it opens the door to an amazing and previously barely uncategorized realm of human health, equivalent to the vast expanse of deep oceans we know so little about, but comprise so much of our planet.

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Copyright Emily Deans, MD