So it never ceases to amaze me that each of us carries around a 3-pound mass of cells in our heads that controls literally everything we do. Importantly though, the brain doesn’t act in isolation from the body, but rather responds to the needs and experiences of each of our organ systems.
Now, here is a staggering statistic that some of you may have heard before.
Our bodies are comprised of 10 times more microbial cells than our own human eukaryotic cells. These microbes, which are primarily bacteria, but also viruses and protozoa, they are part of our normal flora and they make up what’s called the commensal microbiome.
In the intestines there are a hundred trillion of these bugs, reflecting over 10,000 unique species, and contributing 150 times more genes than our own human genomes. It’s even estimated that, collectively, these microbes would weigh 2 to 6 pounds, which is up to twice the weight of an average adult human brain.
More and more we are learning that these commensal microbes that make up us have co-evolved to play fundamental roles in normal brain development and function.
So, we can study the role of commensal microbes by raising mice as completely germ free and recolonizing them with whichever microbes are of interest. And by these types of studies we are learning that commensal microbes regulate several complex behaviors, like anxiety, learning and memory, appetite and satiety, among lots of other behaviors.
So, you can see now that by studying this microbe-brain interaction we can learn really important lessons about how microbes can contribute or affect our brain health and disease.
So, you might be wondering how in the world does the microbe that lives in your gut affect your brain, and there are many different mechanisms.
One way is by activating the vagus nerve.
So, the vagus nerve contacts the gut lining and extends all the way up to the brain stem itself.
And this is the mechanism by which the bacterium called Lactobacillus rhamnosus effects depressive-like behavior in mice. So, in a task that measures depression-related despair mice that have been treated with this bug exhibit less depression-like symptoms, and this is not seen if the vagus nerve is severed.
Another way by which microbes can affect the brain is by activation of the immune system. About 80% of the body’s immune cells reside in the gut, and immune abnormalities contribute to several neurological disorders.
This is one mechanism by which the bacterium Bacteroides fragilis prevents a mouse version of multiple sclerosis. Mice that have been treated with this bug are more resistant to the disease, as shown by the red line in this graph, and this depends on the activity of a special subset of immune cells, called regulatory T cells, that expresses the marker CD25. So if we block the activity of this immune cell then the beneficial effects of the bugs are prevented.
Another way by which bugs can affect the brain is by activating the gut endocrine system. So gut endocrine cells are primary producers of neuropeptides and neurotransmitters.
Gut microbes themselves can also produce metabolites that could affect brain function. And this is one pathway that we think is involved in the microbe-based treatment that we in the Patterson and Mazmanian labs here at Caltech have used to treat autism-like symptoms in mice.
So, by treating mice with this bacterium Bacteroides fragilis we’re able to correct core abnormalities, such as the communication deficit that’s depicted here. That’s a hallmark symptom or diagnostic symptom of autism.
So, here, mice that are autistic-like display less communication, as depicted by the blue bar, and treating them with the bug corrects this effect, as shown by the red bar.
So, I think that the implications of these discoveries is huge, because what if we could, without a single invasive procedure, treat disorders like autism, depression and multiple sclerosis.
Microbe-based therapeutics might offer us a way to build a stable community structure that can impart long-lasting effects without the need for continuous treatment.
Also, since microbes are relatively easy to manipulate, and even eliminate, they can be readily modified for better functioning, regulatory control, targeting and even delivery.
So, as a take-home message, I want you to remember that not only are we made up of mainly microbial cells, but that some of these cells can be truly mind-altering, affecting our brain development, function and even our behavior.
And also, in light of several studies showing important roles of commensal microbes in a variety of biological processes from nutrition and immunity to now brain and behavior, consider all the things that we do on a day-to-day basis to change or disrupt our microbiome and how this might affect our health and predisposition to disease.
