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Gut Microbiota, Host Gene Expression and Cell Traffic via Milk
Josef Neu
Tuesday, Sept. 24, 2019 · 1:32 p.m. · 01h 03m 18s
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that you don and i wanna take both on and the nestle nutritionist to providing the
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so real harder and uh at that it's been a absolute meetings so far at at lower the tremendous amount
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i do want to say that uh uh um this
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lecture is not going to involve as much about gene trafficking
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as things that and actually a lot more familiar with so i'm just gonna get started here with the the agenda
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however briefly talk a about a human knock
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fresh versus don't the donor human not composition
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this is something that is actually quite a an area of a controversy right now
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i'll talk about uh at some the micro by or inhuman knock and its implications
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oh my problem it hello makes the developing intestine microbial effects and the innate and adaptive immune
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systems and multi omit approaches to evaluate micro
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post interactions are so anybody know this guy is
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uh_huh
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yeah out then richard feynman he's a a quantum physicist
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for much help that he won the nobel prize and
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i just want to give a couple of his quality he has a lot of very
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interesting quotes but here is one religion is a quarter of fate sciences the culture of doubt
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we must be careful not to believe things simply because we want them to
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be true or no one can for you as easily as you can for yourself
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yeah and i think that this is very true for many areas that that we've
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been discussing especially uh when it comes to human knock so i'm gonna start with what's
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and i know many of you are basic scientists and there are few union ecologists here
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yeah and i'm just going to ask you for this twenty five we just
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station to be all preterm infant which of the following is are are false
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control feeds should be initiated this is a two days but we're not sure always
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be the first feeding because the mother is often only able to produce small amounts
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they don't remote composition is similar to that the baby's own mother's milk
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and it has clearly been shown in head to head randomised trials
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that paint the room not provide similar benefits the baby's own mother's walk
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okay so two three and four are false
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number one is somewhat controversy oh but i think that over the last few years
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uh most an innate colleges are beginning to control the
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feed low birth weight babies but what should we be feeding
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in two thousand twelve in the us the american academy of pediatrics came up with these guidelines
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the palm benefits of human doctor such that all preterm infants should
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should receive human knock mothers on fresh frozen should be the primary guy
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if the and it should be fortified appropriately for the intent born weighing less than one point part your grapes
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if mother's own no 'cause unavailable despite significant
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lactation support past rise don't remote should be used
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quality control of past rise the window 'cause important and should be monitored
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okay so this is what the uh american academy of pediatrics told us yet ecologist
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and we all started the utmost neonatal intensive care units to this very serious
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and i don't know what the baby's own mother's not was being used it for the was not being used
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so over the next few minutes i want to uh address a few questions first
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can these guidelines potentially lead to heart is their rationale to use mother's
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own of purses don't work what components are lost with routine past resuscitation
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a baked or not and what is the airports and how cool when
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they don't know more like brothers own walk so let's start with potential are
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this is a some work that was done at university floor in armenia intensive sharing it
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and we looked at some data prior to the two
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thousand twelve guidelines and then after the two thousand twelve guidelines
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and here what we're seeing in that this first column is prior to donor milk
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supply implementation and this is a week one two three four five and six after birth
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and here we are looking at the decrease in the percent of all mothers no use so
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what we're saying over here in week one city critics to decrease three degrees all the way down we're
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seeing a decrease in the use of the babies own mother's note and don't know was being used much more
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oh oh probably in these days why well it
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became a much more convenient to use being doughnut
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and uh it was available in the mothers started to believe that out
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this is the same thing the nursing stay happily this is the
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same thing is that babies on others not and so we started to
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uh start questioning this uh this whole perhaps a little bit now what about government
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in the united states don't i'm not this past sixty two point five degrees centigrade from one half hour
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and that actually gets rid of some of very important components
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of this nexus relies that uh at least to some extent
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as far as the composition of don't know and babies on
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mother's not is concerned that they are very different from one another
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this is a a given to me uh that's courtesy
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from uh about computer hartman from university of western australia
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and here we see some the compositional factors in a a a doberman knock in here we see some
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of the things that are highly abolished you're is alkaline
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phosphate case bile salts stimulated like pace almost totally abolish
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with the past relation process i. g. markedly decreased
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so what are the implications of spouse all stimulated light base considered to
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be a very important enzyme in terms of uh hydrolysis subtract was right
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in if you don't get this available you do know here
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for a a the most efficient hydrolysis uh tried was it's
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so that's a that's a an important nutrition now what about
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the output foster case breast not calculate phosphate taste
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decreases over time so here on the x. axis
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we had these post work in here's a good faster pace activity initially quite high and then decreasing
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well what the scalpel pasta tasty there's an intestinal health and possibly taste in there's
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a human knock it has not fast pace it has no pasta taste has the capability
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t. t. phosphor late various probably
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inflammatory microbial components including lightbulb howie saccharine
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that's making them on recognisable by the whole like researchers in as we go
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on this letter you will recognise that a tall but researchers are very important
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outlook pasta taste can directly inhibit the n. f. kappa
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b. pathway components in their bike down regulating inflammatory responses huh
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there are some studies that have been done in animals in mice looking at
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the effects of we combine it calculate facet case on external sites it's so here
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in this study they looked at two outcomes here's the uh body temperature and here's percent survival
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what happens during sepsis in this animal model if you win deuce sepsis by getting l. p.
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s. these animals start getting all like they're beginning to da in here what we're saying is that
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without the uh after possible case these animals start getting quite call
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but the elegant pasta case appears to rescue it here's the survival
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without the eloquent possible case with the l. fast pace so this uh
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uh what i consider to be an important component in the human knock
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our cells live cells are killed in the uh the castration process
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and i'm really not gonna get into the uh uh the cells or not because others have
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already gotten into that and i know that there will be more discussions about this in the future
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oh this uh a conference but i do want to talk more about the microbes knock
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and uh same not really did a very nice job this morning about uh talking about the uh
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what is known about microbes in human not i'll just talk about a little bit
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uh in the past to uh prior to about ten years ago uh
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when we had a knock sample or if we had a mother who
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we were concerned about that the them not might not be right we
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cultured in it we found microbes and that no we would throw it away
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okay now we're beginning to recognise that perhaps uh that that these microbes might actually play a role
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so studies using both culture based on on culture based techniques so that there are in
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duchess microbes in you know in that they could be beneficial as we discussed this morning
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here's the a classic study from hunting colleagues and uh it would
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be able to get in this study and i'll go into this
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a little bit of detail here's really interesting each one of these
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asses represent a different mother so there are sixteen mothers in this study
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we're expressing their nokia one two in four weeks after birth
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and each one of these colours represents different taxes of bacteria
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so in this particular mother as one you can see that the colours are quite similar
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they change a little bit in terms of of their quality and can also mount but
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this mother over time is the these microbes are about the same but they're very different than this mother
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they're very different than this month so there appears to
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be an personalisation of these microbes in these different mothers
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this is work that was done in spain uh looking at the uh of quantity
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uh microbes the total quantity of microbes in the hawk and this
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is the mean plus or minus standard deviations and these are the individual
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but mothers concentrations of knock so here is the call last roll transitional
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in nature milk and you can see some of these mothers have high quantities
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of microbes up to tend to be a michael's per millilitre in their knock this
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is the uh um mean mean quantity so there's a lot of microbes in human knock
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now
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i want to digress a little bit and talk about pro by on x. and this is something that was brought up this morning
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and make how adjusts i don't like to talk about this because
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it's sort of like talking about the president of the united states
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uh if you talk to the wrong people you can get into big trouble okay art but
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yeah what has happened this this is the first going up a hill pushing the
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ball up until this big boulder up they go and in two thousand and k.
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we seem to have a tipping point for pro black some metal analysis came out uh in
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the journal pediatrics and they he had a
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eleven different probably onyx being used in a out
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this a nomad analysis and this net analysis with ease
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ten eleven different probably alex suggested a
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decrease in advertising in ugliness and also death
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and at the end of the discussion section in this uh not analysis paper
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it said something that you almost never hear of the net analysis
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they didn't say more studies are needed they said it's over we
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need to start probably out it's in all of our babies okay
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so this was ten different uh uh uh ten eleven different problematic the uh uh
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species that were being used uh so then the question arises are
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we really they are yeah well several countries started to use this routinely
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and a different problem topics were being used in fact in the united states
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the most commonly use provided is something called laptops that was run doses are cultural
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fifteen percent of the neonatal intensive care units are using
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products routinely to put done advertising it look like this
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but cultural was never even wanna be you know a probe addicts
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that was studied in the uh in that that analysis and so
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the point is that there are different problem uh preparations and no one of them
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until fairly recently has been studied in terms of uh of prevention network
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does you know clips one study that was done in the u. k.
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evaluated around fourteen hundred babies and found no degree since that says nope decrease in
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advertising it replaces or any other adverse on guns so we have one randomised controlled study
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i was asked by the turn what pediatrics to uh discuss the uh shortly after the uh met analysis came out
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uh the routine problematic usage and uh i uh wrote this comment work
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commentary beauty products for pretty printer instance let's be careful
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summer reasons that we need to be careful number one that analyses
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how many data analyses after a couple of years are proven to be false okay the results of proved to be false
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they are especially if they are based on observation studies
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are really small non powered a randomised trials uh or
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pulling next pulling it makes data across trials as if they do you want to a single large trial
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can be a problem especially when you are using different preparations in
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if you are saying that they're all the same which they are now
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uh probably adds a food supplement or drop well it depends
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if you are using can to prevent disease action in premature
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infants if you are using them to be bad disease such as never ties in your like this this is a medical claim
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and this means that they should undergo rigorous testing
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i know that the at the at the european agencies
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do require rigorous testing if you were going to prevent disease
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we also have had some problems in this is just one of the problems
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uh in a a couple of years ago i at yale university
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they started to use products because of the high uh incidence of not good housing erica like this
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and they saw that there was one baby when you dine uh
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and that baby with the path all the g. they look very
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closely and get the whole just down at the baby yeah you
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grew my clothes and a trace that back to the problematic preparation
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and so this is something that is quite scary
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if you don't have correct standards for certain preparation frenzy because they
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are for proper preparation now let's get back to the human nope
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i should you did did you before the illustration that uh he not as high point
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ease of microbes that maybe personalised if you assume intake of eight hundred millilitres per day
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that's not to put a baby uh uh you assume the average number bacterial cells which is tentative to the six
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this will provide about ten the seventy eight bacterial cells daily
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which is close to the those used in most problematic studies so
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your actually providing um next mixture of of microbial agents in the human
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so what about these are they could they potentially be truly personalised well uh if you have a baby
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who is close to the mother and this is a a work that was done by that too well
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and in a published in nineteen seventy nine uh and this system
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that we have heard about before several times the end from memory system
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and if the baby's uh oh are close to the mother
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and if the mother uh it takes up some of the microbes that the baby
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might be columnist by the baby's immune system may not be able to completely respond
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but the mothers immune system it's and these uh a new
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law dylan's cells it's ever will then go into the breast not
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can get into the baby's gastrointestinal tract can provide some potential benefits
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so this is the interim and we system and we've been discussing this
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in terms of both immunology and the types of microbes that might be available
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so in the late nineteen seventies when this was uh uh when this
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review was done i'll have this working from studies that was done in animals
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says that we're gonna animals but i think we're beginning
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to recognise their at least three studies now suggesting that this
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is actually something that does happen in humans this is a study that was done by wrist gonna colleagues in israel
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yeah they look that probably intense with viral disease
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versus controls they look at the notes samples longitude movie
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taken seven days apart while the inputs were recovering from their illness
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and so the analysts the knock samples for c. d. forty five lucas arts mcevoy scott's t. n. f. alpha
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based on that all of those decreased the laptop here and also
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was changed but it was a borderline effect so they concluded from this study
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that this supported by name that nature of immune defence breastfeeding concerts
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so this closeness to the mother sort of like in king who's
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a close just to the motorcade route here our skin to skin here
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may actually be during important in terms of this dynamic interplay between the mother and the baby
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here's a preacher baby the plan that uh we take care of a lot of in the the neonatal intensive
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care unit yeah and uh uh uh at the bottom of the sliding we see a baby with very distended ad
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the baby was developed advertising it replaces one the most
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dreaded diseases that we see in the enable intensive here
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uh the skills about thirty percent of the babies that develop a lot but we know
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about this disease now for over fifty years but we haven't i had that much progress disease
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why well here are some of the reasons we really don't have a
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good definition of this disease yet we lost several different entities into one
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disease that we call network tossing a class but i think we're beginning
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to recognise more more that that were causing your clay says like diabetes
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there's type one diabetes there's type two diabetes and their studies there in between
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so what we are calling advertising it replace is more than one disease
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and we need to delineate and better to find disease before we can move forward
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we have a animal is that were developed in the late nineteen seventies in there are over two hundred
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publications that you can find in pop net using some very this animal
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which does not at all represent what we see in neonatal intensive here
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and we've also focused on individual pathways like the t.
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or work yeah for example which is probably the report
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but we can't just focus on one yeah we we have to focus on in the
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higher system rather than a one yeah so this is where we are going in the future
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uh this picture is a from a a publication that doctor walker
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and i uh wrote in uh i'm just a few years back
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top you can see a baby with advertising iraq latest distended abdomen satiric beamer round belly button
00:21:08
yeah and uh the radiological findings this is uh what we see in terms of
00:21:13
here in the ball well something called tomatoes the test analysis and sometimes we'll actually see
00:21:19
here in the liver a portal trapped labour in this baby ended up getting a
00:21:24
piece of that ball that was taken out fortunately speedy get okay after this research
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so we need to think about this in terms of several different diseases but i would
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like to sort of focus on where the inflammatory disease that we see in preterm babies
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and with this inflammatory disease that we see in preterm babies
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if we look at just station on age of the baby's birth
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we find a difference in terms of the time that in advertising in replaced
00:21:58
it drops so here we have a baby born at twenty three weeks gestation
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here we have a baby born at twenty nine weeks gestation and the question is when
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will this baby develop an advertising replace most likely when will this be developed most likely
00:22:15
well this particular graph has been repeated by several different groups national institutes of health
00:22:22
the uh applied it to a network in the united states called pediatrics with an axe
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uh this is a study that i did with that that remote and partly from the university of a
00:22:32
home from baylor university yeah what we're saying here is that the core rap to just station cajun weeks
00:22:39
his highest between about twenty eight to thirty two weeks gestation
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so what that means is that in all likelihood with its classic
00:22:48
form of number ties in your class this baby would develop it
00:22:52
at about six weeks of age and this big okay at about two weeks after birth we don't know why
00:22:59
this yeah that's why they speak seems to occur but there several speculations
00:23:03
one speculation has to do with the micro basket sure the gastrointestinal tract
00:23:09
similar to the high the micro basket you're the guest guest re
00:23:13
test track might be developing very uh in a very similar wrong
00:23:17
we rarely see right not that the uh prematurely develop prior to three weeks gestation
00:23:23
yes because of the development of the blood vessels in the high the same
00:23:27
thing may hold true for the gastrointestinal tract a doctor walker and after it happened
00:23:35
and showing that there is a whole like receptor for uh that
00:23:39
is present in the gastrointestinal tract that response to libel poly saccharine
00:23:44
that's what i showed you before responding to d. l. o. l. could possibly pace
00:23:49
well that like popeye separate seems to be at its uh the uh to like receptor seems to be at its highest
00:23:56
a concentration in the last part of the second trimester of pregnancy i keep
00:24:03
that in mind as i continue to talk to because this is gonna be upward
00:24:07
what about the microbes they get into the gastrointestinal tract how big how nice the guest test track of this is
00:24:14
a combination of studies this actually met analysis done on sequences
00:24:20
from ten different studies where the uh gastrointestinal tract premature babies
00:24:27
of the the feces was looked at in terms of a sixteen s. sequencing
00:24:32
i packed a penny and i did the study uh initially i didn't think that this could be done
00:24:36
but we could sequences from the different neonatal intensive
00:24:40
care units from boston from universe chicago from cincinnati
00:24:44
uh from various places where uh they had done these studies
00:24:49
in preterm babies and then we looked at the taxonomy over time
00:24:53
here the control babies here than advertising rick likes babies in here we see in the
00:24:58
controls that this blue in this a yellowish
00:25:02
of colour here are some what's similar over time
00:25:07
but over time in the babies with about network
00:25:10
as in iraq latest the blue increases and the yellow
00:25:14
seems to decrease what are the blue blue are of violent bacteria called uh probably a bacterium
00:25:21
the yellow are problem bacteria called affirmative it's we also see over here in the controls
00:25:28
this yellow the the bright yellow at the bottom these are the battery gets so
00:25:32
we see some battery gets over here but the review back to aids over here
00:25:37
so we can speculate on this we don't have any because they already but we can do some speculation
00:25:43
so let's bit speculate a little bit about the probably a bacteria in these
00:25:48
are the bacteria that appeared to increase prior to develop an advertising your clicks
00:25:54
these are brand negative bacteria that are high in like bob holly sack right in their cell walls
00:26:00
and the abundance of probably a bacteria increased
00:26:03
prior to the development and advertising rick likes representatives
00:26:08
but this file on our club c. l. c. thomas equal
00:26:13
high levels might be probably sat right in there so well
00:26:18
here's another from the from the cheats for big shoots actually increase i'm
00:26:25
sorry decrease prior to uh the development that could casino clicks and the producer
00:26:30
largely gram positives and like to be so why are common class of
00:26:34
the uh produce file these are high and like put high court guess it
00:26:39
they also have a a high capability to produce short chain
00:26:43
yeah yes is set yes you read probably on it and acetate
00:26:50
you re there's got to be very important in terms of the fuel for the colon aside puree also
00:26:56
titans judges interrupted below georgians between cells probably on it
00:27:02
but to be very important in terms of the uh of
00:27:05
box p. three system into a production of anti inflammatory mediators
00:27:12
and then the battery beats also thought to be very important remember in
00:27:16
in their babies big easy development because your place very few battery digits
00:27:22
a circus uh uh 'cause 'cause me and has a show and uh there's some work
00:27:27
very good looking at the un backed reads there's a a certain
00:27:32
uh uh immune neural module twenty macho cop
00:27:36
holly saccharine a in the cell wall abuser microbes
00:27:40
yeah and uh these are very uh important the conversion of c. d. four cells into the fox p. three cells
00:27:46
and these regulated production about yeah so these can be in you know module to worry
00:27:52
and these are the so the these are the uh types of
00:27:55
microbes that we're now pressing in those babies that i'll never touching eclipse
00:28:00
so we have kind of an interesting story developing here it's not
00:28:04
proving any kind of course they already but it's an interesting observation association to
00:28:12
so what do we do in the neonatal intensive
00:28:15
care unit get make actually has an advertising it clicks
00:28:20
yeah here we have a pogo cartoon that's as we have met the
00:28:23
and in the in the enemy is us die maybe important human though
00:28:29
maybe some other smokers don't know purses formula that may be very important what about
00:28:33
yeah by i think usage that may be important to or even though whack and trophy
00:28:40
not putting a fuel into the guest retest attract might be important what
00:28:44
what are the most commonly used in a barracks in the labour intensive care
00:28:48
what are the most commonly used cross in neonatal intensive care here we see kind of them up these
00:28:54
at the very top by for jenna mice and and campus
00:28:58
so are the most commonly used uh tribes in the united
00:29:02
states but then just a little bit further down you see
00:29:05
seven taxes they come i see also very commonly used trucks
00:29:10
can this have an effect on the gastrointestinal tract there at least three
00:29:15
studies now suggesting that uh the number of days on again about x.
00:29:21
increases the relative risk for the development of
00:29:24
various adverse outcomes including advertising can require this
00:29:28
so according to this study the average length of treatment which is about seven
00:29:35
days increases the risk of an advertising henrik like this by about fifty percent
00:29:43
this is a boat from a colleague of mine in the innate apologised so i
00:29:47
give a couple days aerobatics to my preterm patients what does that matter if i
00:29:51
change the microbes in the g. i. tract since i could potentially be saving the
00:29:55
babies live back reading and recognised early onset subsets let me just start by saying
00:30:02
babies less than thirty three weeks gestation prior to a couple of years ago prior to some of these uh
00:30:09
a proactive says a quality improvement prejudices that we've been started starting
00:30:15
almost one hundred percent of our very low birth weight babies were getting at about x.
00:30:20
it's slowly beginning to change but they get at least two days of panama x.
00:30:25
so what does this do when they get at least two days of any blacks
00:30:29
well here what we're saying is treated babies
00:30:33
your controls these are different attacks of bacteria
00:30:37
and we see that in the controls we see here's the
00:30:40
probably bacteria uh he and i'm sorry here's the um the the
00:30:47
for kids in the controls and in the treated
00:30:52
i'm having a hard time reading this yeah there's a a marked difference here's the uh uh probably a bacteria
00:31:00
in the controls much larger probably a bacteria in
00:31:04
the uh uh treated animals in in the controls
00:31:07
you find a similar relationship at week eight so today
00:31:12
it's about about x. shortly after birth will alter the microbiology
00:31:18
four weeks anyway anyway at eight weeks at washington university partner
00:31:23
were in colleagues have shown back to even up to first year
00:31:28
you had ended microbial resistant microbes more so in those babies were
00:31:34
treated with antibiotics then you do in the uh not rigged up
00:31:40
two months ago this paper came out of uh oh and and it
00:31:44
was a published in nature medicine and that this was a very interesting study
00:31:49
that looked at i. g. a. and we were talking this morning about microbes that
00:31:53
were coupled to antibodies these are the
00:31:57
study evaluated microbes coupled to i. g. eight
00:32:01
yeah and they did flow site on the tree and look at the stools uh babies
00:32:06
uh who were being formula fed versus getting their own mothers knock
00:32:12
can hear what we see is that uh uh more i ga
00:32:16
in those babies who were getting their own mothers know compared to formula
00:32:21
okay here we're looking at uh oh the uh and has no bacteria
00:32:27
bound total intestinal bacteria bound by i. g. a. okay and this is time
00:32:33
after delivery and the x. axes here we see the formula fed babies
00:32:37
here we see the maternal not with babies and here we see this increase
00:32:42
where you didn't see this increase over here it's pretty much the same because
00:32:46
these babies were getting b. i. g. a. in their mothers no this is
00:32:51
probably get the impasse snow i. g. that's being produced by the babies on a test
00:32:57
here we see not good housing or aquinas controls versus
00:33:01
the not proposing replace babies and we see much lower
00:33:06
i ga bound microbes can be not babies are here we see the types of bacteria
00:33:16
can not causing reply this baby's purse the controls in here they look at the
00:33:21
bacteria at a family level before i showed you the bacteria end of file on level
00:33:26
here we see the control back to really see which is at the family level much higher in the
00:33:31
network housing replace babies well what about specific yeah to control back to really see bound to i ga
00:33:38
here we see the uh oh intestinal bacteria in the uh controls
00:33:45
and here's the neck babies these are about the same in here
00:33:48
the p. crease over time for the pictures the lower a binding
00:33:53
in an advertising recording space so some very interesting studies that suggest the other differences in i.
00:34:00
g. a. i i know that the uh we're gonna hear more about this uh tomorrow afternoon
00:34:05
um now what about see section versus backchannel to leverage this is something that was brought up several times in this conference
00:34:13
not stalk backed babies were born by backchannel delivery will pick up a bashful microbes uh
00:34:20
in their mouth and these will get into the baby's gastrointestinal tract candidate harness the gastrointestinal tract
00:34:27
can those babies were born by c. section delivery do not undergo this process
00:34:33
there are several studies that have been done that seem to support this view
00:34:38
here's probably one of the more classic studies done by a detriment but the makers
00:34:42
bellow from n. y. u. this was a study that was done in a a venezuelan
00:34:47
yeah i was gonna actually very few subjects but
00:34:50
you can see clustering of see section two little babies
00:34:55
they had mother stand over here and here we see clustering of the
00:34:58
bed actually deliver babies tools and the uh oh uh of the badge or
00:35:05
microbes okay suggesting that the those babies to uh went through
00:35:10
the budget and i had a badge on microbes in the still
00:35:17
so this lead to something very interesting this is a paper that was published in uh
00:35:21
need to notice and will be over a year ago in the title of this
00:35:25
was partial restoration of the micro by
00:35:27
or assyrian board intensity a banjo microbial transfer
00:35:32
so what you do with this well if you have a mother who
00:35:37
delivers by syrian section you put a swab into that mothers with john
00:35:43
and then you take that's walk after you leaving after leaving it there for about an hour and you swap the baby smell
00:35:50
and the tapes and adjust and they found that they could actually
00:35:54
get the backchannel microbes into the newborns gastrointestinal tract by doing this
00:36:03
there are many parents they're beginning to ask obstetricians to do that's okay but
00:36:13
we've been a little bit afraid to begin to initiate this this is
00:36:17
the american college of o. b. g. y. n. in two thousand sixteen
00:36:22
can i just want to read the red party we we recommend against the
00:36:25
practised the backchannel seating until better data are available establishing the safety and benefits
00:36:32
of this preface so just imagine if a mother had been recognised herpes virus infection
00:36:39
and if you inoculated that a baby with the herpes virus infection
00:36:44
that would be primary herpes in the baby could potentially die from
00:36:48
that certainly that's not something that we want to do to her babies
00:36:55
last week this article came out in nature
00:36:59
stunted micro by over an opportunistic cabbage in conversation ensues
00:37:03
syrian section birth okay if any v. c. newspaper yeah
00:37:08
that's a fascinating paper on here is uh some the data from that paper
00:37:15
the lip remote seems to make a big difference in
00:37:18
terms of the mike microbiology developed but the question that
00:37:23
i was brought up by sender top of this morning was what about in a buyout use
00:37:29
well almost all mothers with the liver by syrian such and get in the blacks
00:37:34
around the time see section delivery and they did have a somewhat of an effect
00:37:40
post natal stay in the hospital seem to have an effect a breast beating seem to have an effect
00:37:46
hospitals like there are many different factors that were associated with
00:37:50
c. section to liberate not necessarily the c. section itself up interest
00:37:56
was the fact that in this study the bacteria that they saw ah
00:38:01
in the bay actually delivered babies did not consist of a large quantity
00:38:06
of the lack to the so i that you see in the backchannel trap
00:38:11
saw other kinds of bacteria here are some of the battery that
00:38:13
they saw can here we see in the bad we deliver babies
00:38:19
you can see this pattern and in the c. section deliver babies you see this pattern so there
00:38:26
are some real differences early on from four to seven
00:38:30
days but then twenty one days they begin to even out
00:38:33
then infancy they look very much the same but even
00:38:36
at eight months the back credits appear to be significantly more
00:38:41
oh they're probably present in the uh uh a batch
00:38:44
really deliver babies compared to the c. section deliver babies
00:38:48
i still think that there's a lot of confounding factors in
00:38:51
this study and we have to think about the uh us stay
00:38:55
in the hospital a baby who was the word processor impact that
00:39:00
section not only gets the antibiotics compared to the battery delivered baby
00:39:04
but that baby stays in the hospital for several days longer
00:39:10
then the baby who is covered by national deliberate okay but types of microbes
00:39:16
that they were saying in the c. section delivered babies were hospital might rocks
00:39:22
club c. o. equal rights or
00:39:26
so that's certainly something to uh take take into consideration slow initiation
00:39:32
of breastfeeding also may be very important those babies were born vice
00:39:37
assyrian section the mothers do not provide the same amount of press
00:39:40
knock early on as do the babies were but actually the lever
00:39:45
so it may take a little longer for that seating to occur it for the uh types of microbes and
00:39:51
the other components oppressed knock that may actually promote a
00:39:56
that mike viola in the uh human not to develop
00:40:01
this is a study by making as out from canada and i just want to
00:40:04
uh show you here well uh this is a very small number of subjects she has
00:40:09
actually done a more work recently but these are
00:40:13
uh but actually deliver babies syrian section deliver babies who are
00:40:17
not breastfed at four months you see a difference in the microbiology
00:40:23
but those who are plastic bag you see very little
00:40:27
difference in the micro by suggesting that breastfeeding seems to
00:40:32
reverse this a flat out see section or stay in the hospital or whatever areas in
00:40:38
o. c. sections over babies that are causing differences in the microbiology or so in the future
00:40:46
some questions can the microbes in human knock over come and about induced or
00:40:50
other forms of this bios us that are associated with not purchasing it requires
00:40:54
kinda microbes in human knock over come the hospital environment effects associated with c. section deliveries
00:41:01
should we be focusing on the use of fresh mother's milk rather than baked dollar bach
00:41:06
and can we improve our side projects are just getting two copies areas here
00:41:12
work that we did at the university for just a couple of years ago uh involved the question
00:41:18
abdominal purses babies on mother's knock we know that there's a very rich microbial and uh
00:41:25
oh no you can uh babies on others no but oh no 'cause
00:41:28
pass trust a lot of mothers can now produce a lot of knock
00:41:35
right after birth and so is it possible that we might be able to take some of
00:41:40
that small quantities of the babies on mother's knock and put it into they don't or rock n.
00:41:47
develop a composition of microbes that is very similar to that of the babies owners knock
00:41:55
so this was called a transplant nation process and uh out
00:41:59
with value weighted the uh oh quantity of microbes in the
00:42:03
a baby so mothers not using both culture based and not culture based techniques and we also
00:42:09
use not quarter based and quarter based techniques and the donor not found almost no microbes in the
00:42:14
a dollar not in terms of live microbes but we were able to find microbial b. n. a. and they don't know
00:42:21
so here is a don't know versus a baby so mother's milk
00:42:25
and you can see that babies on mother's milk as more microbes
00:42:28
a different types of microbes and i can't see that's library well but
00:42:32
in this study the major result was incubation don't unlock with ten percent
00:42:39
mother's own knock for forty eight hours resulted in levels of microbes
00:42:44
very similar to that of mother's own knock down by both a culture and not culture based techniques
00:42:52
so that's one way we could potentially improve the microbial environment but we have to also
00:42:59
show that matters in the future so we might be doing something that just doesn't
00:43:03
matter at all but we have to shop future what about improved scientific approaches well
00:43:12
when we do micro by on studies when we
00:43:14
do make apple mac studies uh hobbies show associations
00:43:21
this is a problem
00:43:24
we can look at or do you know we can look at or micro by um
00:43:27
we can look at them it had the lights we can look at the aperture no uh
00:43:31
we can look at them singly but this is only association
00:43:37
type of work so here is um interesting story this is
00:43:42
a um a old hindi um i think it's handy um
00:43:49
a parable a a ad
00:43:53
good uh presentation should be susceptible to only one interpretation um
00:43:59
i'll read this to you it was six men of industry to learning much inclined who went to
00:44:05
see the off like the all of them were blind to each by observation might satisfy his mind
00:44:11
the first felt the side i said this is like a wall
00:44:16
the second felt the task and said this is very like a spear the third felt the truck this
00:44:22
is very like a snake before thought any this is very like a tree the fifth filled in here
00:44:29
it is my i cafe yeah this sixth i felt like a rope
00:44:35
and so the minute in the industry disputed long long long loud and long
00:44:40
it's in its own opinion exceeding stiffen strong each was partially in the right and all were in the wrong
00:44:48
so this is an area that i think we need to just
00:44:52
not just look at one a a component like the uh microbial and
00:44:57
we need to look at multi on x. and we are now getting
00:45:01
the bile confirm attic technologies to help us look at multi on x.
00:45:09
so why do this each individual type of only data
00:45:12
may provide a list of differences associated with the disease
00:45:16
individually they can be useful but analysis of only one
00:45:19
data type is limited to correlations mostly reflecting reactive process these
00:45:24
checking rape first argument rather than cause it to
00:45:26
once these can be hypothesis generating but no hypothesis testing
00:45:34
these are fishing expeditions as one would here in a study section at national institutes of off
00:45:40
integration of different omits data types more strongly
00:45:43
identify patterns associated with appropriate better associate with
00:45:47
and perhaps or even closeted the disease and this can more readily lead to disease treatment targets
00:45:54
so i'm going to talk just spend a few minutes here on antibiotic induced this bios number i said before
00:46:02
that we have some problems with uh getting a lot of data back store premature babies
00:46:08
and also to mothers as sam said this morning this gonna do something called
00:46:12
a display o. says what are we really doing with these uh enter bark treatments
00:46:18
at the university of order we uh i had the a fortune of having a um
00:46:23
small uh national institutes of health grant to do what the first randomised controlled studies of
00:46:30
and about x. in preterm babies and it was
00:46:33
a ah study that was called a pragmatic randomised trial
00:46:38
there are certain babies that me an ecologist would never agree not to give an above text
00:46:43
okay this was a high risk group over here about uh so if the mother had a definite core you and you know this
00:46:50
fever of thirty nine degrees centigrade we would have to get in
00:46:54
a box to those babies but here we have this group here randomised
00:46:59
group group see where one group they were either randomised to get anabolic
00:47:04
score to not get into products i just wanna show you a little
00:47:08
glimpse of the data that we're getting and this is attempting to get multi on x. data on these babies
00:47:15
so here at the top user somewhat complex diagrams but here are the top we see the end of biologics that
00:47:22
were used this a baby who back and about x. was randomised to get in the backs early on in the course
00:47:28
okay so you see different about excuse uses over time
00:47:32
with this uh babies a hospital corps peace circles here represent
00:47:37
but my crops this tool microbes and the different colours are different packs of microbes
00:47:44
first still the cornea can see very low diversity
00:47:50
the size here is done in an exponential scale and that is the total number
00:47:55
of microbes the total microbial quantity and you can see the top microbial quantity here increases
00:48:02
we see some changes with the use of a aerobatic so here's a a and about usage in here
00:48:09
we see this shift in the types of microbes here
00:48:12
we're looking at a different uh i can't inflammatory mediators
00:48:16
and down here we're looking at the table next here i'm just looking
00:48:20
at the beach or i guess it but you can see putrid guess it
00:48:23
changing over here depending on the use of uh either the type of know
00:48:28
that the baby is getting or the aerobatics so this is very complex and
00:48:33
here is another baby that did not get aerobatics right offhand again the cornea
00:48:40
fairly high quantity of microbes but very low diversity that begins to change over time here the baby
00:48:48
that's an aerobatics because the nato just thought the baby was getting sick you can see a major shift
00:48:53
in the types of microbes here the baby goes from a donor
00:48:57
breast milk to formula and we're seeing different types of microbes over here
00:49:03
here's the inflammatory mediators this tool here's the obliterating the stool
00:49:08
just different way a different way to look at this from
00:49:10
a more multi omit perspective i and here's the tablets in clustering
00:49:17
and here what we're seeing is uh here is the uh randomised group
00:49:22
uh that is getting at about the that that is getting at about
00:49:25
the this is the group that it's it's definitely getting aerobatics the middle here
00:49:29
these are the babies whose mothers have korean unites
00:49:32
and here's the group that was randomised to uh
00:49:37
getting aerobatics and no getting it back so you can see that these three groups you're very different from
00:49:42
one another so the use of in a box changes in the table in the gastrointestinal tract these babies
00:49:52
in the future we also want to look at transcript comics how we look at transcript comics in
00:49:59
what you can't do biopsies on these days but we have some colleagues uh
00:50:04
at texas a and m. they're able to uh get slapped at the real cells
00:50:09
and there were able to look at the microbial transcript comics in the slot that the feeling
00:50:14
also also in the future we hope to add transcript comics to these set to the studies
00:50:20
so let's put it all together and uh here's some of the considerations for design of multi or make studies
00:50:27
these are best in that complex process caesar diseases
00:50:30
not those were known single genes or bacteria cause disease
00:50:36
these are really gonna be a challenge to do these types of studies but i think that they are
00:50:39
possible complex diseases develop over time several type points
00:50:44
need to be considered especially when you're talking about babies
00:50:49
by outbreaks are needed because usually large number of samples are needed
00:50:53
sample size determinations needed before collection of data
00:50:58
so i'm gonna summarise here there's numerous by what the factors including light microbes microbial components
00:51:04
in human knock but they're actual function we need poorly understood their based associations
00:51:10
rather than causal mechanisms so we have so lot of circumstantial versus direct evidence
00:51:17
study using multi all mixed the future will better provide cause
00:51:21
of mechanistic evidence in human studies we may not need to go
00:51:26
to a drug free animals and some of the studies that have been
00:51:29
done in cell cultures where we have to take a leap of faith
00:51:33
i'd like to acknowledge many people who have had the opportunity to work with over
00:51:37
the years and funding sources and thanks to uh the people i work with and uh
00:51:42
a new nail intensive care unit at the university of florida thank
00:51:45
you for your attention we have a little bit of time for questions
00:51:56
yes
00:51:59
and that's wonderful ah f. anything i think and uh if you kick ah yeah yeah
00:52:06
at the time same pattern matcher lactation change
00:52:09
with downright time now for a gestation into everything
00:52:15
ah okay that's a that's a a really good idea uh in
00:52:21
i know that when i visited spain a few years ago a
00:52:24
couple years ago uh that there was an attempt to to do this
00:52:28
of where they were actually trying to out match uh be
00:52:32
lactation wage with the uh uh uh with the particular baby
00:52:36
um so i think that's a that's a great idea uh the problem is that you know the notice still guess tryst
00:52:44
we don't have that but the same factors and don't know because we have a big you don't smoke
00:52:53
yes
00:52:57
thank you for under four lecture ah on my
00:53:01
own are often hank and yeah yeah sound at heart
00:53:06
so it was a fee on my grandma and grandpa colour and and the beginning i'll on the v. c.
00:53:14
so to your second question figaro uh transplants for
00:53:19
uh uh try to prevent microcosm replies no no that
00:53:22
has not been done uh it's been discussed how and
00:53:26
i think that there's a lot of discussion now about
00:53:29
finding consortia of michael's not actual peak of microbial
00:53:34
transplants but actually finding the right consortia of microbes
00:53:38
oh that may be a up working to the other uh to provide a beneficial thing
00:53:45
not just those one or two or three up robotic agents
00:53:50
on your first question uh the bile marks for the disease up there
00:53:55
are some vile markers but i think until we get a better idea
00:54:01
of what the definition of the disease actually yours
00:54:04
and separate out the different sub categories of this disease
00:54:08
are we going to be able to use the buyer markers to any uh um reasonable extent
00:54:19
uh_huh
00:54:20
ah thank you very much for your nice an elimination act last give what is that
00:54:26
policy in your unit ah and getting a really self very low but then an extremely overpaid
00:54:34
who doesn't have any added factor in the mother i didn't really very often for julie
00:54:40
do you use a i mean profiling and it might take are you
00:54:44
don't know you don't use any you you know it it is yeah so
00:54:49
can premature babies look very what they and it's very well versed late eighties oh
00:54:55
if you would've asked me that question five years ago i would have said they all get and about six
00:55:02
now it two thousand nineteen we are having something does that we're getting
00:55:07
very selective about and we're beginning to be a little bit more cautious
00:55:11
so if the mother does not have risked their lives if the baby is born it's yeah oh
00:55:18
which for twenty seven twenty weeks gestation and looks fairly good even if the baby has to go on the chemical elevation
00:55:25
oh we're watching those babies very closely and not necessarily treating all
00:55:30
of them with their barracks right in our unit we have seen
00:55:34
that baby is looking very good in there and the first one or two or three years
00:55:39
and apparently will develop and ah respect is just syndrome everything is working fine
00:55:43
amount per day for the the baby's getting you know reluctant if you can rent extension assigns upstairs
00:55:50
and that again when you when you you have to start
00:55:52
again interacting and your imminent local news on obviously i guess not
00:55:57
so i mean i still right is that is that ah
00:56:01
and you have a at yeah alaska might provide an excuse
00:56:05
uh i will be i believe are receiving and divided
00:56:10
are not receiving and you might but in terms of survival
00:56:13
i do have any you any data and yeah i mean in terms of well supplied elevating using actually backing
00:56:20
i think that we are not using providing can't you might ah no
00:56:25
no we don't have that data in terms of survival without the prophylactic aerobatic usage
00:56:30
uh would just beginning to ask a question right now but in terms of uh just to give you an example
00:56:37
uh the study that we did on advertising reckless uh looking at the micro biology at the university sort of we have three different hospitals
00:56:43
we obtain samples from nine hundred babies and uh we did what cultures and all of those nine hundred
00:56:50
babies one percent of them at possible of cultures can
00:56:55
several of those were probably contaminants so in other words
00:56:59
the local the local search don't help us much this is of
00:57:03
real conundrum uh and so uh should we even be doing this
00:57:08
at the beginning so i i i do understand what
00:57:11
you're saying uh it occasionally we'll have a baby who uh
00:57:16
ends up developing signs of success getting sceptre
00:57:21
it may even be concept but are you which we all of
00:57:25
those days we had one baby with other steady who uh we
00:57:31
actually was randomised to not getting about x. but the baby started looking a pretty bad within about
00:57:37
four hours and we build that baby out we did have the opportunity to build a baby yeah
00:57:41
oh that baby start at about x. we get the baby episode agenda mice and baby dot
00:57:48
but the baby died of a boat that was resistant to have this orange advice
00:57:55
so even though we gave the baby at about eighty
00:57:59
had resisted attempts to have my camera i pauses for them
00:58:03
hum there might be some other cause the middle you know these which we're like
00:58:06
yeah sure and have the same yeah but directly under cause of of of that uh
00:58:13
yeah i have yeah thanks generally great talk yeah i comes from new castle right chi just
00:58:20
ask about oral antibiotics remember that was here is is that it's twenty is good showing reduction neck
00:58:27
and it's part of a large corporation we discover state showing that the babies
00:58:32
don't guarantee politics have become very cynical and politics actually high risk of neck
00:58:38
it's a given that uh and that seems to be associated with this sort of gloom of protein bacteria
00:58:44
do you think might still be role full
00:58:47
time in counterproductive bacteria way if potentially orally administered
00:58:53
trent mice or something like this for a few days the studies that
00:58:56
were done this is a thirty years ago um you know the old
00:59:04
so the studies were done around thirty years ago and that there there were i think
00:59:07
three or four of them that look at rock and my son overall jenna mice and
00:59:11
yeah and uh uh they were really small stays
00:59:15
very underpowered studies and uh at one of them was
00:59:20
done at the university of order i was not involved with that but was that at the university of florida
00:59:25
and one of the things that occur we they they started getting a whirl kinda
00:59:28
mice and uh uh routinely to all the babies in the in a latency period
00:59:35
they started to see resistant microbes and the resistant microbes did not
00:59:40
only occur that they started seeing it not only in the neonatal intensive
00:59:43
care unit but other parts of the hospital as well so that
00:59:48
cause us to uh have a lot of uh reservations about continuing to
00:59:54
but in a in a in a pickup morals that a person
00:59:57
killed just on the most effective intervention for for preventing neck or is
01:00:02
oh and politics but then uh yeah robotics for everything else let me let
01:00:07
me say uh uh i was brought up earlier in this uh conference that
01:00:13
certain animals have a very different immune system condition
01:00:18
yeah and i remember working on pick what's uh many years ago
01:00:22
when uh we were looking at a cholesterol macros membrane of these animals
01:00:28
and uh we would deliver them by serious action taken into
01:00:34
a clean environment can within one week they would be getting
01:00:39
and we would have to get i don't let those animals have one no feeding or given any local argument
01:00:46
they did not get that transfer through the a plus and as we humans do so
01:00:50
i think that this is a different immune system and i have a hard time uh
01:00:57
really uh uh i should say the leading i i
01:01:01
think that they're well done studies it's just that the whole
01:01:05
a premise of the study is it's it's very different than human
01:01:11
or or you know um parent when you mentioned a. l. g. g. for prevention often advertising fridays
01:01:19
i'm aware of one study which showed that there was absolutely no effect on a concrete enlightening creation
01:01:26
and selfish or infection or um i don't know
01:01:29
dish on an nah sydney australia they used to
01:01:33
provide onyx or you know i'll and apparently they're using them routinely now you know what is the current
01:01:40
as bad as our prevention of neck in out of
01:01:43
studies emission and in the centres well i i there are
01:01:48
in terms of uh um the usage of the crowbar uh in the us as i mentioned
01:01:56
about fifteen percent a neonatal intensive care units have been using products
01:02:02
uh the most commonly use products is the lack of a source rendell says uh this studies
01:02:08
that have been what you said have not shown a a a decrease in advertising in a class
01:02:15
one study that was done at emory by robert to tell this was a study where they looked at uh giving
01:02:23
no products and then starting with the back to the source rendell says your uh two different times box
01:02:29
they can make the incidence of not good housing a request actually increased
01:02:34
after starting the like the source from knows us with two different products
01:02:40
uh in four and a lot in europe there was a one study that showed almost the same thing is the emory study
01:02:47
that uh if you look at the uh oh probably activists whack a bit a problematic in this direction
01:02:53
versus yeah provided menstruation or was it an increase
01:02:58
but that's not been seen uniformly and all studies
01:03:03
so it's just something that i think we owe notations ah now
01:03:07
on take a coffee break if you have additional questions you can astral
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Milk Microbiome and Neonatal Colonization: overview
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Human Milk Microbiota: Origin and Potential Uses
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Human Milk Virome
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Gut Microbiota, Host Gene Expression and Cell Traffic via Milk
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Breastmilk and Microbiota in Protection from NEC in Prematures
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Sept. 24, 2019 · 3:01 p.m.
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