Tuesday, November 20, 2012

Microbiome Part 9: The Finale--Bacteria and Mood

Note: This program first aired on November 17, 2012.

This week, we wrap up our exploration of bacteria and the microbiome with a final look at the world within us; the cutting edge of human microbiome research. What scientists are discovering is the fact that the bacteria in your gut can influence your mental state. So not only do they digest your food, synthesize your vitamins, regulate your immune system and keep their pathogenic brethren in line, they also strongly influence how calm, anxious, bold or depressed you might happen to be.

Several recent studies on mice have demonstrated this effect quite clearly. In one study, the behavior of “normal” mice was compared to mice who were fed a diet that included a probiotic supplement. The probiotic mice proved to be less anxious and more confident in behavioral tests, and had lower levels of the stress hormone cortisol in the their urine.  In another study, two different strains of mice were compared, one bred to be passive and timid and the other bold and courageous. When bacteria from one mouse strain were transplanted into the other mouse strain, the “transplantee’s” behavior changed to match the behavior of the donor mouse strain. In other words, putting bacteria from a passive mouse into a bold mouse can make a bold mouse passive. Putting bacteria from a confident mouse into a timid mouse can make a timid mouse confident. This shows that the personality traits we have come to think of as having a genetic basis (the scientists who bred those strains of mice certainly thought that), are in fact quite plastic and seem to depend on composition of the gut microbiome rather than genetic code.

In a rather circular piece of logic, it also seems that the mind can influence the population and diversity of the gut flora as well. In times of stress, gut flora becomes less diverse and robust, creating openings for more serious dysbiosis and disease—think of it as an extreme case of butterflies in the stomach. So the bacteria influence the mind, and the mind influences the bacteria, and around and around the maypole they go.

So how does this work? The literature refers to the rather heady “brain gut enteric microbiota axis”, but the actual mechanisms of communication are not completely well known as of yet. A few things are quite clear. The gut houses a huge amount of nervous system tissue, so much so that it is commonly referred to as our “second brain”. This second brain is connected to our first brain by the vagus nerve, a large bidirectional nerve pathway that originates in our brain stem and invenerates almost all of our viserca*. Most of the neurons in the vagus nerve are sensory, they collect information about the state  of the viserca and send it back to the brain. The remaining neurons carry info from the brain back to the viserca. In the first mouse experiment I discussed, the one with the probiotic-ed mice, when researchers severed the vagus nerve in those probiotic supplemented mice, the treatment effect vanished. So the probiotics may still have been in the gut, but the anxiety reducing effect of them could no longer be communicated to the brain. This tells us that at least in that experiement, the vagus nerve played a huge role in communicating whatever the probiotic bacteria were doing.

It has also been noted that the nervous system tissue in the gut produces many significant neurochemicals, including all the big ones like serotonin, dopamine, GABA, norepinephrine, and acetylcholine. It turns out, the gut bacteria make these chemicals too, many of which down regulate the excitability factor in the brain leading to enhanced calm. What isn’t clear is if it is really the bacteria that are responsible for the neurochemicals that we always ascribed to the nervous system tissue in the gut. And the actual means of communication between the gut and brain has not been fully parsed out. The vagus nerve is clearly part of it, but these neurochemicals must play a role as well.  And all of this has huge implications for medicine and treatment of everything from mental illness to autoimmune diseases.

The day is coming when your personal ecosystem will be easily assessed, imbalances identified and addressed, and health restored, all on the basis of your individual mix of microbial flora. I personally am incredibly excited about this, and look forward to the day when we in western medicine, work with our microbiomes, instead of exclusively against them, acknowledging our place in the much bigger we are just a part of. The tide is turning.

*Everything except our spleen, for some reason…


Gut bacteria and mood—the mouse study

Gut bacteria in infancy determine happiness (via serotonin levels)

Gut bacteria and anxiety and depression

A great overview from the American Psychological Association and Dr. Siri Carpenter, Sept. 2012 http://www.apa.org/monitor/2012/09/gut-feeling.aspx

The show that started all this wondering for me, RadioLab. Take a listen here: http://www.radiolab.org/2012/apr/02/gut-feelings/

Emmanuel Denou, Wendy Jackson, Jun Lu, Patricia Blennerhassett, Kathy McCoy, Elena F. Verdu, Stephen M. Collins, Premysl Bercik. The Intestinal Microbiota Determines Mouse Behavior and Brain BDNF Levels. Gastroenterology, Vol. 140, Issue 5, Supplement 1, Page S-57