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