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  • 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)

It never ceases to amaze me

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B2 中高級

TEDx】改變心靈的微生物:微生物組如何影響大腦和行為。蕭亞軒在TEDxCaltech上的演講。 (【TEDx】Mind-altering microbes: how the microbiome affects brain and behavior: Elaine Hsiao at TEDxCaltech)

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    Han Hun 發佈於 2021 年 01 月 14 日
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