Transcriber: Marta Gysel
Reviewer: Ariana Bleau Lugo 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 is called
the commensal microbiome. In the intestines there are
a hundred trillion of these bugs, reflecting over 10 thousand
unique species, and contributing 150 times more genes
than our own human genomes. It is 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 extents 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 is 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
(Laughter) to change or disrupt our microbiome and how this might affect our health
and predisposition to disease. Thank you. (Applause)
