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Or infighting here and then being able
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to talk about well there's already
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alluded to the causality of the micro
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by women in in the metabolism. So I
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thought it would be nice to structure
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the discussion about around what I
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think are unanswered questions. And
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problems and all lead you through the
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way we think you should we we we think
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that it's a good way to to approach
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these problems. And then we can discuss
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later about what it it's right away or
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not twenty to agree that it's still not
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knowing what it is of course rule and
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what I wrote don't really your all the
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time let me see my point that works
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yeah is about small just remarkably
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other which I'll actually was like
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later which I think I'm more involved
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order proximal column part are more
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involved in metabolism and the fickle
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sample. We still don't know what are
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expect your aorta metabolites for
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example short chain for acids that have
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the adverse or thirty effect. And we
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have to probably and produce anaerobic
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material strange that large quantities
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and there's not so much technology at
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the transfer that has to come as well.
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So first I would like to have a little
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bit about how we think that causality
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works in terms of metabolism member
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using course postulates. Um so all
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these studies that you have been
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hearing which are fantastic and really
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set the stage that I think for no other
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disease there so much evidence that
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that market we or our fourth and
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they're really well well written
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papers. I think what they don't take
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can mind is the following and so that
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when you eat in your small intestine
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this is the part where you take your
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proteins you could usual order you're
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shorting fit yes it's just really do
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them in a modulation here's all the
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immune system you do literal opiate of
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four to five and there's only a couple
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bacteria couple hundred fifty
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ridiculous whereas lower lower down and
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the and gastrointestinal tract PH is
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rising there many more bacteria but the
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function is different basically because
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for what we know from literature is
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predominantly absorption of war and the
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production of shortening fatty acids
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and my point is that if we're looking
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at their critics we we would need to
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know the material which are living here
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basically because they are my directly
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be orchestrating this update of glucose
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and cholesterol and they might also
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have to live here to have the
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beneficial effects for example
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metabolite production. So that's I
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think a very important thing to realise
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the other thing which we have to
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realise that's really don't know when
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we seem to be a person batteries the
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nine which means that the only has
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repeatedly or maligned obesity which
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means that they have in some resistance
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in a very high risk of developing
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complications. And eventually a
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premature that what we do know and that
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is that the first thing I would like to
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show you is that we do have the face
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throughout opposed issue. So that this
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acquisition nearly intestines it's it's
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she seems to be causing involved in in
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driving insulin resistance and making
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people malign obesity. So we know from
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us cat scans that you have much more
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facial adequacy sure so does that
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position you got are much more prone to
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develop into resistance in type two
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diabetes and once that's dominant leads
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to detainees at a postage we know that
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information of this fits Oedipus issues
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important. So we were wondering women I
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what are driving fax for example
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because your transportation might be
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involved in this phase radical social
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information. So we used corpse spouses
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for causality. And I'm a medical doctor
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unlimited amounts can probably all if
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you are familiar with his postulates of
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this very famous spectral that is to
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set that for example for pneumonia if
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you want to to show that pneumonia
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scoring team caucus first you have to
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find these Newman caucus in the in
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flames long. So that's exactly what we
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did. We went into the surgery room
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people went up for for for also for I
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don't know surgery. And we took in them
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subset of patients you well classified
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and they were not a medication all of
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our trolls none of the people are
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medication every tube messenger bistro
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and postage for mental at a post issue
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and subroutine is and of cost issue and
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there's there are conditions. And what
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we did and what will the then is just
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look where you could find a material
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signature in that Oedipus tissue
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depots. And interestingly enough only
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in esoteric vessel at bus station not
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executing as opposed to should not in a
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mental Oedipus issue we found one
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specific dominant strain which was
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Rolls stillness pieces. So we're all
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only RB I knew a little bit about it
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from the clinic because you hear it's
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an emerging infections especially
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people who are in in in mean a
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compromise for example in a alpha your
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kidney transplant patients and usually
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disaffection goes via drinking water.
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It's appropriate material and it's a
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gram negative wrote and we know three
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different pieces newman's to be their
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money so you have to get the ending CE
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o.s. So what we did then it's just to
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some correlations as everybody does
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between the amount of brownstone yeah
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in the interface for adequacy issue any
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amount of trust only are these three
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strings of Russell interfaces and we
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found that only also you getting some
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significant linear correlation. So that
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men and the other two didn't so it
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means that the more of distrust on you
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have your face for adequacy to you more
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you have it in the features and we also
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found that the amount of a still yeah
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in this this ride posting should be no
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correlated with you my last see your P
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which of course is a marker for
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information consequently when you look
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at at connecting which is which goes
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down you have inflamed at most issue we
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funded inverse relation so that was
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quite a convincing for us. So use the
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second thing what you should do when
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you follow court also that is that you
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need to find in association so for
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example if there's more animal carcass
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around more people get get pneumonia.
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So that's what we did together with
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rhetoric. So here's this court of well
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metabolic phenotype that will be
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females of which a subset develop type
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two diabetes a subset remain normal
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classy making a subset was in between
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and we look in their P C.s only for
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also need to get a because we thought
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that that was the string that was
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interesting to follow what are that
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would predicted presence of type two
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diabetes in in the in the subjects that
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have type two diabetes or compare
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insulin glucose tolerance we found two
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fold increase of distrust only a
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interfaces and we also find this
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inverse relation between you mount will
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still inefficiencies and and connecting
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level showing that even if we see do
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you money first on the S communicating
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we think three unopposed issue
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resulting in this act but then the
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final part of course course which would
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be that you read that you re in future
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re that you give back this micro
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organism and reproduced minute. So
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that's what we did. Um will cultural
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stoning and we give back to mail deal
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mice for weeks everyday if are sinners
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to make because we want to know for
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sure that would get there we didn't
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wanna put it into drinking water we
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wanted to give specific amounts of
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distrust only in in the that these mice
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it is for four weeks and we compared to
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placebo which was least rule "'cause"
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we stored all stone yes minus eighteen
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this what we find is that the mice that
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got lost on got more use compared to
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the placebo and we also find that the
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mice that got the roles Sony about more
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insulin resistant as compared to
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placebo and then finally because I
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would like to provoke a little bit of
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the discussion rule talking about their
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critics and probably a ducks but if you
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think about how usually infectious
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diseases are treated it's about
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vaccination. So what we thought this if
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we can prefix in a ton of the pen don't
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have time to show you all the data but
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how we did it if we camp repost human
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system with this you can activate it's
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an indicator of are also you get you
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can we can prevent the development of
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of insulin resistance when we treat
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these mice for which of course only and
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indeed which you can see is that the my
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support GT forty active Ross Tonya got
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diabetes the once we got the heat
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inactivated rust on yeah less diabetes
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and once I got three vaccinated and you
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can almost remain to the normal DO
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insulin resistance instant sensitive to
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have so by sharing that of course what
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we're doing this is more of a
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pathological approach but are also
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looking at their critical facts because
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I'm a clinical darker I've no
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experience in so much and sequencing I
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really admire what we can do one it's
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not rocket science just using the
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fickle transplant and that also is
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something that we didn't find at my
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first patient I treated was to to see
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if patients and I just went on Google
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to find and then found fickle
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transplants and there's very nice paper
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showing that that indeed the people
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present emerge from china in the fourth
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century as well and said it was used to
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treat food poisoning and diarrhoea and
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in the nineteen thirties if you would
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go to the middle east would get candle
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P C.'s T as welcome gift to prevent you
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from getting traveller's diarrhoea if
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you stated them. And then in the
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nineteen fifties there was a first
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publication by surgeon who said you
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could cure and the other can use
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diarrhoea just by giving if people
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still transparent. So how does it work
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I think it's a very there's lots of
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debate about what we do is just a
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morning stool sample was brought by the
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dollar. It's mixed into the five
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minutes each other like solution of and
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what we do is either we always effusive
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I I I guess to one or two which allows
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us here which allows us to also take
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biopsies when we're there and was what
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I understand is that in most US subject
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there's rectilinear used which then
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doesn't cover small intestine lots of
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debate of whether it's safe or not yeah
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but we screen according to about the
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nation protocol and an know to nine
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fifty patients we didn't have any side
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effects yet so from that but other case
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reports have been reported because of
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this as as as you can appreciate from
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internet theirs do it yourself eagle
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transmit movies on you to verify two or
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three minutes you know how to do it
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yourself. And it's and it's a tragic
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because I'm the pros maybe once a week
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by patient one step people trenchant
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for observation or anything and usually
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I'd like this also happened to this guy
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went to mass general to get a fickle
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transplant force all sort of sorts of
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colitis. And you didn't get that so we
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use this to his own son of two years
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old and infuse it any ended up one week
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later at the house with the with the
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seems equaliser so it's not that say
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you really should use it in a in a in a
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sick way this is very known to you we
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we we started was that if because I
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think this is the only a condition
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where you can really really changed for
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long term the microbial a composition.
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And better than medication as well and
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said ninety percent success rate first
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thirty percent than we are I think this
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is very important because came about
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all the time. It's talking about
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diversity so you can see that the
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patients I was see at a very low
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diversity basically it's a desert there
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the the owners very racial diversity
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and after the people transmitted
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remained up to the level of the donor
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with the diversity until ninety days at
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least there were almost no side effects
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as I said I mean in chronology just and
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a very much interested in metabolism
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you metabolism. And what we'd end it is
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can we use the transfer of inter so
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microbial or from the subjects into
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treatment lives so no medication
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patients who got consumers is metabolic
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syndrome basically one people
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transplant there was no adverse effect
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and after a baseline and after six
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weeks will look addressing energy
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expenditure and insulin plan with
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stable as to what we found is this and
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I'll take you through the slides a
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little bit slower so we look that's
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preferable and that insulin sensitivity
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bit for taking time boundaries focus
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now on Bristol insulin sensitivity
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which means how sensitive the muscle is
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for taking up the look so what you can
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see here is that healthy donors are
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very concerned sensitive and a donor
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sort of metabolic syndrome subjects of
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a very suppressed insulin sensitivity
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of course your insulin resistance if
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you give back the owns two after six
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weeks nothing happened but if you give
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the donor theses back you can see that
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it increases the insulin sensitivity to
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the level of the dollar. And even more
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interesting is that if you look at
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individual responses not all dollars
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have the same effect some dollars
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really haven't affected the patient is
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a steep increase in their insulin
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sensitivity whereas other donors have
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no effect and we see this of possible
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fickle transcript that we do undersea
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give for faster information or other
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diseases like enough advantage then we
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also looked at people got microbial
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composition because we think it's
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important that we don't think it's
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driving from we used stadium by William
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this he map meaning that red means that
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the bacteria what we need to take a
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dollar machine see only very fake
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colour so it means not so much happens.
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But if you look at what's happening
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after the leaned don't know fickle
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transfer many you great producers are
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increased and it's only sixteen so it
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really brings us using this people
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transcript just to look at the needle
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in the haystack we also looked at the
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small decimal by at baseline after six
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weeks just to see what happening what's
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happening there. But you can see is
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after the given back trophies is the
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colour I went up where is it went down
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after evening donor fickle trends but
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what we found an increase in the user
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to highly I I a small intestinal
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inhabitants and the increase was
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associated with increased insulin
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sensitivity sorta more insulin
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sensitivity in in the diabetic patient
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the more you between probably we found
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in that patient in this one test taking
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one step back before we go to the
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probably other approach which we use
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with your highly I is that already
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alluded to I think it's very important
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that we distract what it's the bacteria
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or their products and so what we did is
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you know you hear all about eight and
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short chain fatty to being so
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important. So there are indeed a that
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if you give you rate so that's the
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product of the beneficial but your
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edited improve insulin sensitivity and
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rather fat activation in in mice with
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diabetes and as I said we would like to
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see whether that also reproducing
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humans so what we did is we give you
00:14:10
and four programs pewter eight which we
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estimated to be to fifty percent of the
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daily produced amount once again we
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give for four weeks also got four weeks
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everyday anyone losing no medication we
00:14:22
given orally because I really want to
00:14:24
be the small intestine be involved in
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that as well not only by recollection
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what we found any seven patients still
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ongoing because it's an open label try
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that we found that the peripheral
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insulin sensitivity went up. And the
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and the patients sore in the in the
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subjects and the person and the button
00:14:43
insulin sensitivity went up as well but
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not as much as the muscle sensitive
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when we delegate brown that so we used
00:14:50
with the LC D.s can we look at what's
00:14:52
happening with the brown fat in the
00:14:54
subject before and after treatment you
00:14:56
can see here that all this brownish
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kind of thing a black kind of thing
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it's brown that activation we found we
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need a significant activation of the
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prophet an increase in FT have twenty
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one eight eight marker which is
00:15:08
associated with profit activation and
00:15:11
sympathetic neural activation mice we
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find it humans as well. So in the next
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five last minutes I'll show you about
00:15:18
wow why we think that the feature as
00:15:20
one might be important in finding new
00:15:23
there you take someone colon probably
00:15:24
from now. So as the first I summoned
00:15:28
the surgeon who said that that I think
00:15:30
these interviews published about fifty
00:15:32
being effective in in in the diary I
00:15:35
already said that it's much more static
00:15:37
to give the pure cultures and we got
00:15:38
that all the time during this for
00:15:40
during the other fantastic colours. So
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I don't think it's a it's a fantasy I
00:15:45
think to you can use it as research
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model you shouldn't start a clinic in
00:15:49
and giving FT people kind of diseases
00:15:51
we focus on small intestinal biopsy
00:15:53
because that's the part where we think
00:15:55
that this procuring can really sore
00:15:56
five just a mix passage in the solution
00:15:58
and can get that and and and that if
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the basic. So what we did what I'll
00:16:03
show you a security how yeah and it
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produces shorting fair yes it's it's
00:16:07
it's a grandpa selecting or confused at
00:16:10
the lobby ice small testing and other
00:16:12
other high PH at the colour and
00:16:14
insensitive to thank the mice and so if
00:16:16
you wanna give it to you mentioned you
00:16:17
want to have an anti don't because to
00:16:18
get a sepsis from it you can at least
00:16:20
read it's so bad that we wanted to give
00:16:23
it immediately to humans and then Darby
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said that's too fast that was two years
00:16:27
ago first your those those dependent or
00:16:30
those funding try and then come back.
00:16:33
So that's what we did we did a very
00:16:35
simple those finding trial in DVDB mice
00:16:37
a per group once again this data
00:16:39
devices PC soon went to the the mice
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and everyday input the data files with
00:16:44
with frozen of the pros and you holy I
00:16:48
versus so with increasing those use of
00:16:50
these off to see how I situation versus
00:16:53
placebo. We dated for four weeks and we
00:16:55
looked what's happening eight what
00:16:57
expect here would really get there in
00:16:59
the in the intestine and we found a
00:17:00
need that didn't see come of the
00:17:02
treated my sticky holly I was
00:17:04
relatively getting more buttons so it
00:17:06
was increased when you give you holly I
00:17:08
for four weeks in the C come of the
00:17:10
mikes. So it's getting here. So that we
00:17:13
looked at functionalities of dusty
00:17:14
honey I improve or affect your insulin
00:17:16
sensitivity in these mice. So for that
00:17:19
we use very well. We use it is equal
00:17:21
adjust all the time insulin tolerance
00:17:23
test which means that you give a
00:17:24
specific amount of insulin and usually
00:17:27
when your parents are incensed if your
00:17:28
glucose goes that that's exactly what's
00:17:30
happened after the my sticker treated
00:17:32
with with the you have the idea that do
00:17:34
go spend on meaning that there were
00:17:36
insulin sensitive compared to the ones
00:17:38
that are treated with placebo is there
00:17:40
to Lucas didn't go down. So they were
00:17:42
insulin resistance. So we thought is
00:17:44
very interesting but it's always good
00:17:46
checked around eight and at that time
00:17:47
rhetoric allowed me to do or to to have
00:17:51
one of these posters repeat the
00:17:52
experiment and got to work using a clap
00:17:54
sort of the call centre of insulin
00:17:56
sensitivity and we also did something
00:17:58
else. We compare a lively holly I
00:18:00
versus you can activate it in highly I
00:18:02
not only the blissful as you need next
00:18:04
if you holly I to see whether that had
00:18:06
affect or not you metabolic pages and
00:18:09
that's a set that number and harbouring
00:18:11
swim plan we found that you hardly I
00:18:15
after actually how I went up not so
00:18:18
much after he'd inactivated to
00:18:19
treatment there was no effect on body
00:18:21
weight development and the mice didn't
00:18:24
eat less compared to there is an
00:18:26
activated control. So for us we think
00:18:28
that that means that at least it can
00:18:29
get so sick when we look at the energy
00:18:32
expenditure as I said we think that the
00:18:34
more energy you burn the better it is
00:18:36
for you. And you can see that the mice
00:18:38
that were treated with the active holly
00:18:39
I got more resting energy total energy
00:18:42
expenditure compared to the mice that
00:18:44
were three to heat inactivated control
00:18:47
and if we look that plan once again
00:18:49
what's happening with the peripheral
00:18:50
insulin sensitivity you can see it's
00:18:52
well it's on the borderline of
00:18:54
significance in these in these rather
00:18:56
small group but you can see it improves
00:18:58
the insulin sensitivity mice. We think
00:19:01
it's not so much fire shorting
00:19:02
suggestions because as you can see in
00:19:04
the theses there's not I mean there's
00:19:06
things happening but it's not what you
00:19:08
would expect that the massive amount of
00:19:09
sure of so you rate is produced but we
00:19:12
do see a shift in bile acid production
00:19:14
we see that in a three holy out
00:19:16
treatment you see less primary about
00:19:19
it's it's more secondary bile acids
00:19:22
which at least another human studies
00:19:23
are associated with more beneficial and
00:19:25
metabolic control. So then we got
00:19:28
exception from Nairobi to do it. And
00:19:31
that brought us to another thing how to
00:19:33
culture at large quantities how to get
00:19:36
a stability because you have to give
00:19:37
for four weeks to patients are the
00:19:39
compliance but that this time we're
00:19:41
doing this randomised sorry this those
00:19:43
finding placebo controlled trial face
00:19:45
want to win metabolic syndrome with the
00:19:47
GMP produce the holly I and William
00:19:49
already showed you this this is figure
00:19:52
it it is just an example of what many
00:19:54
strange that will follow that are able
00:19:56
to intervene in the printer market we
00:19:58
know that as I said there will be many
00:19:59
other strange we hope that giving back
00:20:02
simple strains it it pushes back the
00:20:05
diversity or at least pushes back to my
00:20:07
line obesity to the health would be
00:20:09
sitting. So we're doing this and this
00:20:12
is just the the the the the conveyor
00:20:14
belt that we're using all the time
00:20:15
we're doing many people trends that the
00:20:17
NC all randomised controlled trials it
00:20:19
see below control because we think
00:20:21
there's a much larger see both effect
00:20:23
IBB is now finished it somebody guess
00:20:25
trend relatives we're looking at type
00:20:26
one diabetes Neville Nash and not
00:20:29
resistant bacteria always to find which
00:20:31
small and large intestinal bacteria are
00:20:34
involved and even more important I
00:20:36
guess just to see what are what are
00:20:40
there some kind of association with
00:20:42
hard and points are not so much a
00:20:44
questionnaire but for plant for
00:20:46
instance sensitivity of fatty liver
00:20:47
disease we do biopsies before and after
00:20:49
treatment. So this is I guess the
00:20:52
discussion I think there is at least
00:20:54
one metabolism cultural we use court
00:20:56
also because it helps us together hands
00:20:58
around it. And you should and also
00:21:00
remotes perspective multicasting floors
00:21:03
I think I showed you an example that's
00:21:05
good started the bacteria or the
00:21:07
product that is doing the trick and
00:21:09
it's vaccination in the long term might
00:21:10
might do it. And that he hardly I which
00:21:12
is using a reductionist approach first
00:21:14
one strain and we're gonna add in other
00:21:16
strange to see whether it adds
00:21:18
complexity auditors really is simply a
00:21:20
duck mechanism with that I would like
00:21:22
to thank you. And think also the
00:21:24
grandkids including the argumentation
00:21:26
for the followup studies and open

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Conference program

Introduction of the Session 1 : The Gut Microbiome: Facts and Figures
Josef Penninger, Institute of Molecular Biotechnology, Vienna
23 Oct. 2014 · 9:07 a.m.
The role of commensal bacteria in the gut
Willem de Vos, Wageningen University, The Neterlands
23 Oct. 2014 · 9:31 a.m.
Q&A : The role of commensal bacteria in the gut
Willem de Vos, Wageningen University, The Neterlands
23 Oct. 2014 · 10:29 a.m.
Gut microbial richness impacts human health
Dusko Ehrlich, INRA, Jouy-en-Josas, France
23 Oct. 2014 · 11:07 a.m.
Q&A : Gut microbial richness impacts human health
Dusko Ehrlich, INRA, Jouy-en-Josas, France
23 Oct. 2014 · 11:44 a.m.
Cross-talk between the mucosal immune system and environmental factors
Hiroshi Kiyono, The University of Tokyo, Japan
23 Oct. 2014 · 11:56 a.m.
Q&A : Cross-talk between the mucosal immune system and environmental factors
Hiroshi Kiyono, The University of Tokyo, Japan
23 Oct. 2014 · 12:31 p.m.
Introduction of the Session 2 : Host - Microbiome Interaction
Susan Suter, University of Geneva, Switzerland
23 Oct. 2014 · 1:41 p.m.
Mechanisms of cross talk in the gut
Annick Mercenier, Nestlé Research Center, Lausanne, Switzerland
23 Oct. 2014 · 1:55 p.m.
Q&A : Mechanisms of cross talk in the gut
Annick Mercenier, Nestlé Research Center, Lausanne, Switzerland
23 Oct. 2014 · 2:34 p.m.
Relationship of diet to gut microbiota diversity, stability and health in older people
Paul O'Toole, University College Cork, Ireland
23 Oct. 2014 · 3:52 p.m.
Q&A : Relationship of diet to gut microbiota diversity, stability and health in older people
Paul O'Toole, University College Cork, Ireland
23 Oct. 2014 · 4:27 p.m.
Gut microbes and their role in malnutrition and obesity
Rob Knight, University of Colorado, Boulder, USA
24 Oct. 2014 · 9:16 a.m.
Q&A : Gut microbes and their role in malnutrition and obesity
Rob Knight, University of Colorado, Boulder, USA
24 Oct. 2014 · 10:01 a.m.
The gut metagenome - your other genome
Jun Wang, BGI, Shenzhen, China
24 Oct. 2014 · 10:19 a.m.
Q&A : The gut metagenome - your other genome
Jun Wang, BGI, Shenzhen, China
24 Oct. 2014 · 10:53 a.m.
Fecal transplant to mine for novel probiotics
Max Nieuwdorp, Amsterdam Medical Center, The Netherlands
24 Oct. 2014 · 11:04 a.m.
Q&A : Fecal transplant to mine for novel probiotics
Max Nieuwdorp, Amsterdam Medical Center, The Netherlands
24 Oct. 2014 · 11:25 a.m.
Introduction of the Session 4 : Nutritional Interventions
Keiko Abe, The University of Tokyo, Japan
24 Oct. 2014 · 12:46 p.m.
Interactions between gut microbiota, host genetics and diet
Liping Zhao, Jiao Tang University, Shanghai, China
24 Oct. 2014 · 12:56 p.m.
Pediatric intervention - what works and what doesn't work
Hania Szajewska, The Medical University of Warsaw, Poland
24 Oct. 2014 · 1:47 p.m.
Q&A : Pediatric intervention - what works and what doesn't work
Hania Szajewska, The Medical University of Warsaw, Poland
24 Oct. 2014 · 2:15 p.m.
Perspectives for nutrition and the gut microbiome
Nicholas Schork, J. Craig Venter Institute, La Jolla, USA
24 Oct. 2014 · 3:02 p.m.
Q&A : Perspectives for nutrition and the gut microbiome
Nicholas Schork, J. Craig Venter Institute, La Jolla, USA
24 Oct. 2014 · 3:46 p.m.

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