LiveGDX Webinar Supporting Gut Barrier Function Sept2017

00:59:31
https://www.youtube.com/watch?v=Gmx3yslJv9Q

摘要

TLDRWebinar led by Dr. Thomas Williams discussing the importance of gut barrier function in health. The session covers the mechanisms of gut health, the role of the gut barrier in nutrient absorption and immune response, and dietary influences on gut permeability. Dr. Williams emphasizes the need for a balanced approach to gut health, including the use of dietary supplements and lifestyle changes. He also addresses common questions about gut permeability, leaky gut, and the impact of various dietary components on gut health.

心得

  • 🩺 Dr. Thomas Williams is the guest speaker.
  • 📚 The webinar focuses on gut barrier function.
  • 🌱 Dietary influences are crucial for gut health.
  • 🔬 Gut permeability can be measured through specific tests.
  • 🍏 A diverse diet supports gut barrier function.
  • ⚠️ Avoid NSAIDs to protect gut health.
  • 🧪 Leaky gut refers to increased intestinal permeability.
  • ⏳ Restoration of gut health varies by individual.
  • 📖 Dr. Williams' book is available for purchase online.
  • 💡 Probiotics may benefit gut barrier function.

时间轴

  • 00:00:00 - 00:05:00

    Webinar introduktion av Michael Chapman, moderator, och Dr. Thomas Williams, expert inom molekylär immunologi och kosttillskott. Presentationens fokus är på att stödja tarmbarriärens funktion.

  • 00:05:00 - 00:10:00

    Dr. Williams presenterar sin bok om funktionella strategier för hantering av gastrointestinala störningar, med fokus på tarmens skyddande barriär och dess betydelse för hälsa.

  • 00:10:00 - 00:15:00

    Diskussion om tarmens gränssnitt och barriärfunktion, inklusive vikten av att ha en effektiv barriär för att skydda mot miljöfaktorer och upprätthålla immunförsvaret.

  • 00:15:00 - 00:20:00

    Betydelsen av HPA-axeln, immunsystemet och GI-systemet som samverkande enheter i hanteringen av stress och sjukdomar.

  • 00:20:00 - 00:25:00

    Tarmens barriärfunktion beskrivs som en komplex kommunikationssystem som tillåter selektiv passage av ämnen, vilket skapar sårbarhet för patogener.

  • 00:25:00 - 00:30:00

    Genomgång av tarmens celltyper, inklusive enterocyter, Paneth-celler och immunceller, och deras roller i att upprätthålla barriärens integritet.

  • 00:30:00 - 00:35:00

    Skillnader mellan tunntarmen och tjocktarmen i fråga om struktur och funktion, med fokus på absorption och fermentering.

  • 00:35:00 - 00:40:00

    Diskussion om tarmmikrobiota och dess påverkan på tarmbarriärens funktion, inklusive fördelar och potentiella risker med olika mikrober.

  • 00:40:00 - 00:45:00

    Introduktion av begreppet 'läckande tarm' och dess koppling till autoimmuna sjukdomar, samt vikten av att förstå tarmpermeabilitet.

  • 00:45:00 - 00:50:00

    Mätmetoder för tarmpermeabilitet, inklusive laktulos-mannitol-testet, och hur dessa kan användas för att bedöma tarmens hälsa.

  • 00:50:00 - 00:59:31

    Avslutande tankar om kosttillskott och livsstilsförändringar som kan stödja tarmbarriärens funktion, inklusive glutamin, probiotika och antiinflammatoriska livsmedel.

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思维导图

视频问答

  • Who is the guest speaker for the webinar?

    Dr. Thomas Williams, an expert in molecular immunology and dietary supplements.

  • What is the main topic of the webinar?

    Supporting gut barrier function.

  • Where can I find the presentation materials?

    The materials will be available on the Genova website within a week.

  • What are the five main areas covered in Dr. Williams' book?

    Digestion, microbial ecosystem, neural endocrine functions, elimination and detoxification, and protective barrier.

  • What is the significance of the gut barrier?

    It serves as an interface for nutrient absorption and immune response.

  • How can gut permeability be measured?

    Through tests like the lactulose-mannitol test and ex vivo biopsy methods.

  • What dietary components can support gut barrier function?

    Glutamine, probiotics, phytonutrients, and avoiding NSAIDs.

  • What is 'leaky gut'?

    A condition where the gut barrier becomes permeable, allowing substances to pass into the bloodstream.

  • How long does it take to restore gut health?

    It varies by individual, but improvements can be seen in weeks to months.

  • Where can I purchase Dr. Williams' book?

    Through the Lifestyle Matrix Resource Center.

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  • 00:00:01
    hello everyone and welcome to our
  • 00:00:03
    webinar entitled supporting gut barrier
  • 00:00:05
    function our guest speaker today is dr.
  • 00:00:08
    Thomas Williams my name is Michael
  • 00:00:12
    Chapman and I'm a medical education
  • 00:00:13
    specialist at Genova Asheville branch
  • 00:00:15
    and I'm gonna serve as the moderator for
  • 00:00:17
    today's webinar and we'd like to welcome
  • 00:00:21
    dr. Tom Williams dr. Williams earned his
  • 00:00:23
    doctorate in molecular immunology from
  • 00:00:26
    the Medical College of Wisconsin in
  • 00:00:27
    Milwaukee for the past two decades he
  • 00:00:30
    spent his time investigating the
  • 00:00:32
    mechanisms and actions of lifestyle and
  • 00:00:34
    nutrient based therapies and as an
  • 00:00:36
    expert in the therapeutic uses of
  • 00:00:38
    dietary supplements thomas serves as an
  • 00:00:40
    adjunct assistant professor at the
  • 00:00:43
    University of Wisconsin School of
  • 00:00:44
    Pharmacy and is the VP of science for
  • 00:00:46
    orthomolecular products since 2014 he
  • 00:00:50
    has been writing a series of teaching
  • 00:00:51
    manuals that outline and evaluate the
  • 00:00:53
    evidence for the principles and
  • 00:00:55
    protocols that are fundamental to the
  • 00:00:56
    functional and integrative medical
  • 00:00:58
    community he is the founder and director
  • 00:01:01
    of the point Institute an independent
  • 00:01:03
    research and publishing organization
  • 00:01:04
    that facilitates the distribution of his
  • 00:01:06
    many publications a frequent guest
  • 00:01:09
    speaker dr. Williams provides training
  • 00:01:11
    to a variety of health care disciplines
  • 00:01:13
    in the use of lifestyle and natural
  • 00:01:15
    medicines he lives in the woods outside
  • 00:01:17
    Stevens Point Wisconsin with his wife
  • 00:01:18
    and children one of the most common
  • 00:01:21
    questions we get asked during the
  • 00:01:22
    webinar is about availability of this
  • 00:01:24
    presentation in the slide deck these
  • 00:01:26
    materials will be available on our
  • 00:01:27
    website within a week of the webinar and
  • 00:01:29
    if you're interested in having these
  • 00:01:30
    resources please click the clinicians
  • 00:01:32
    tab on the homepage where you'll find
  • 00:01:34
    access to our webinars under medical
  • 00:01:36
    education or you can also log to your my
  • 00:01:38
    DG DX account to find these webinars if
  • 00:01:41
    you do not have a my GDX account please
  • 00:01:43
    click on getting started link on our
  • 00:01:44
    homepage
  • 00:01:46
    now I will turn it over to dr. Williams
  • 00:01:50
    I appreciate the opportunity to give
  • 00:01:54
    this webinar today on a topic that's
  • 00:01:57
    obviously very interesting and very
  • 00:01:59
    important for the functional medicine
  • 00:02:02
    community and obviously the patient's
  • 00:02:03
    that they serve so as was mentioned this
  • 00:02:08
    is information that comes out of one of
  • 00:02:11
    the recent books this was published last
  • 00:02:12
    year
  • 00:02:13
    functional strategies for the management
  • 00:02:16
    of gastrointestinal disorders we're
  • 00:02:17
    going to cover not all of this obviously
  • 00:02:20
    but you can see on the right-hand side
  • 00:02:22
    the four main are the five main areas
  • 00:02:23
    that are covered within this book from a
  • 00:02:27
    functional standpoint digestion or
  • 00:02:28
    absorption the microbial ecosystem of
  • 00:02:31
    the gut neural endocrine functions
  • 00:02:33
    elimination and detoxification and of
  • 00:02:36
    course the protective barrier or
  • 00:02:37
    interface is what we're going to kind of
  • 00:02:39
    cover today obviously in the 45 minutes
  • 00:02:42
    or so we have I'm not going to cover
  • 00:02:44
    every detail but I want to give a
  • 00:02:46
    highlight of kind of what we know about
  • 00:02:49
    where we can influence the barrier
  • 00:02:52
    function of the gut we can test for that
  • 00:02:55
    and then the very limited information
  • 00:02:57
    that we have about things that we know
  • 00:02:59
    function in in changing the the barrier
  • 00:03:04
    function of the gut in ways we can
  • 00:03:06
    measure so the idea of a barrier or
  • 00:03:09
    interface is really a you know universal
  • 00:03:12
    to all biology almost everything happens
  • 00:03:15
    at an interface whether it's the you
  • 00:03:18
    know the discrete different functions
  • 00:03:20
    between the inside and outside of a
  • 00:03:21
    tissue a cell and organelle a gene a
  • 00:03:24
    gene even has a beginning and an end we
  • 00:03:27
    know there's interfaces between the
  • 00:03:28
    promoter region coding region etc so
  • 00:03:30
    these interfaces are where we have all
  • 00:03:34
    of the organization all of the the
  • 00:03:39
    control of what happens in and outside
  • 00:03:42
    of that that system so and in order to
  • 00:03:44
    have a good interface we have to have a
  • 00:03:46
    barrier so if there is no barrier
  • 00:03:48
    between one side and the other the
  • 00:03:50
    interface obviously is of no use so if
  • 00:03:53
    you have a you know exquisite gate in a
  • 00:03:55
    wall that is supposed to control what
  • 00:03:58
    happens on each side of the wall
  • 00:04:00
    obviously it doesn't work if if the
  • 00:04:02
    barriers can completely destroyed so if
  • 00:04:06
    you go back to looking at these
  • 00:04:08
    interfaces or these places where we we
  • 00:04:12
    look at larger pieces of the way the bot
  • 00:04:14
    the body looks at surveilling risk or
  • 00:04:18
    risk from the environment you can see
  • 00:04:21
    these are three areas that I spend quite
  • 00:04:23
    a bit of time on the HPA axis and the
  • 00:04:25
    stress response the
  • 00:04:26
    UHN system and the GI system and if you
  • 00:04:29
    look at how they interface with one
  • 00:04:30
    their each one of these is a broad
  • 00:04:33
    interface that allows us to deal with in
  • 00:04:36
    the case of the HPA access stress from
  • 00:04:38
    outside the body and getting information
  • 00:04:41
    from the inside to get kind of give us
  • 00:04:43
    this idea of an overall stress response
  • 00:04:46
    the immune system is supposed to give us
  • 00:04:48
    this interface between self and non-self
  • 00:04:50
    and finally the GI tract is really this
  • 00:04:53
    large interface with the outside world
  • 00:04:55
    as we're going to see and it signals and
  • 00:04:58
    coordinates the immune system and the
  • 00:05:00
    brain and really all three of these are
  • 00:05:02
    related together and interestingly if
  • 00:05:05
    you look back at Hansell yays work on
  • 00:05:07
    the stress that he put in animals he
  • 00:05:10
    defined his stress response as an
  • 00:05:13
    alteration in the HPA access including
  • 00:05:16
    hypertrophy the adrenal gland atrophy of
  • 00:05:18
    the thymus so a change in the immune
  • 00:05:20
    system function and erosions in and or
  • 00:05:24
    ulcers and de la denhams a change in the
  • 00:05:26
    GI system so this was really the
  • 00:05:28
    coordinated definition he had he had and
  • 00:05:33
    he obviously looked at a number of
  • 00:05:34
    different things that said that this was
  • 00:05:36
    quintessential to a dysfunction in the
  • 00:05:40
    stress response or the surveillance
  • 00:05:43
    systems of the body so it's not
  • 00:05:44
    coincidental that these three are tied
  • 00:05:46
    together and it's one of the reasons why
  • 00:05:48
    I always see these three areas the HPA
  • 00:05:51
    axis the immune system in the GI system
  • 00:05:53
    is being highly coordinated in chronic
  • 00:05:56
    disease management and in many cases
  • 00:05:58
    acute disease management as well so as
  • 00:06:03
    we think of an interface especially when
  • 00:06:04
    it comes to the gut we want to think of
  • 00:06:07
    a couple different things here I wrote
  • 00:06:10
    this in I think in the beginning of the
  • 00:06:13
    book or on beginning of the barrier
  • 00:06:15
    chapter of the book that talks about not
  • 00:06:17
    imagining the barrier function is
  • 00:06:20
    meaning just something that keeps things
  • 00:06:22
    out but a sophisticated system to
  • 00:06:24
    communicate with and allow selective
  • 00:06:26
    entry of certain contents from the gut
  • 00:06:28
    lumen into the body requiring a tight
  • 00:06:30
    control but a thin barrier of tissue and
  • 00:06:33
    secretions intentionally designed for
  • 00:06:36
    close proximity to the gut lumen one of
  • 00:06:38
    the things that we need to think about
  • 00:06:39
    here in
  • 00:06:40
    that if the gut wanted to be just a
  • 00:06:42
    barrier it would be a much better
  • 00:06:44
    barrier the reason that the barrier
  • 00:06:46
    function of the gut is so tenuous
  • 00:06:49
    sometimes is because it's designed we
  • 00:06:51
    have cloaks close proximity to the gut
  • 00:06:54
    lumen because it needs signals it needs
  • 00:06:57
    nutrients it needs access to that
  • 00:06:59
    environment which is a very which
  • 00:07:02
    creates vulnerability to those same
  • 00:07:03
    microbes toxins and immunological
  • 00:07:05
    reactive components so I think that's
  • 00:07:08
    really an important feature of this
  • 00:07:10
    concept we need we probably need to
  • 00:07:13
    eventually use the word interface even
  • 00:07:15
    more so than barrier so obviously the
  • 00:07:19
    gut is designed for that system and one
  • 00:07:22
    of the ways it does that is by greatly
  • 00:07:24
    expanding its surface area so we see not
  • 00:07:27
    only the the GI tract creating these
  • 00:07:31
    large villi but then we have these micro
  • 00:07:36
    villi that greatly expand the surface
  • 00:07:38
    area if you just take the cells
  • 00:07:40
    themselves people say you know it's
  • 00:07:42
    about the size of a tennis court or
  • 00:07:43
    doubles tennis court obviously that's a
  • 00:07:45
    huge area for which the immune system
  • 00:07:48
    has to spread out and and protect sort
  • 00:07:53
    of like a castle wall it has to be sort
  • 00:07:55
    of a way to protect the whole thing all
  • 00:07:56
    the time when we have a vulnerability in
  • 00:07:59
    the case of you know an extreme case
  • 00:08:01
    like celiac disease where we have hyper
  • 00:08:03
    inflammation we see villous atrophy we
  • 00:08:06
    see an atrophy of the surface area and
  • 00:08:08
    obviously that has negative connotations
  • 00:08:11
    and negative consequences but that
  • 00:08:13
    actually is an adaptive response to the
  • 00:08:15
    protective mechanism of the oven the
  • 00:08:19
    barrier function if you have a tennis
  • 00:08:21
    court and you can shrink that down you
  • 00:08:24
    know into half that size you have half
  • 00:08:27
    the barrier to protect against and so
  • 00:08:30
    again this creates a benefit for some of
  • 00:08:33
    the interface functions but of a greater
  • 00:08:35
    vulnerability as well so if we think of
  • 00:08:38
    the functional components of the gut
  • 00:08:40
    barrier we have human GI cells we're
  • 00:08:42
    going to talk about those typically we
  • 00:08:44
    think of those as the entero sites and
  • 00:08:45
    the colonist sites we think of that is
  • 00:08:48
    this quote single layer of cells that
  • 00:08:50
    protects us the gut lumen from
  • 00:08:54
    the inside of the body we have obviously
  • 00:08:56
    the whole human immune cells that line
  • 00:08:58
    the inside or penetrate the interface
  • 00:09:00
    itself so we have those cells that we
  • 00:09:03
    want to think of as part of the gut
  • 00:09:05
    barrier we have neural endocrine cells
  • 00:09:08
    and neurons with synapses nearby so they
  • 00:09:10
    actually help communicate the barrier
  • 00:09:13
    function to the brain and the brain to
  • 00:09:15
    the barrier function so we have some
  • 00:09:18
    interface with neural endocrine cells we
  • 00:09:21
    have secretions from many of those cells
  • 00:09:23
    so we have secretions like mucus
  • 00:09:25
    secretory IgA antimicrobial peptides
  • 00:09:28
    enzymes acid neurotransmitters these are
  • 00:09:31
    all secretions that become part of the
  • 00:09:33
    gut barrier itself and finally we have
  • 00:09:36
    non-human microbes in the lumen and
  • 00:09:39
    mucous lining and so we think of these
  • 00:09:41
    is obviously commensal or passel bias or
  • 00:09:43
    potentially pathogenic bacteria viruses
  • 00:09:46
    both free BET viruses and bacteria
  • 00:09:48
    phages that are in bacteria fungi
  • 00:09:50
    non-human eukaryotic organisms maybe
  • 00:09:53
    some of those will be determined to be
  • 00:09:56
    commensals so there as we will see we
  • 00:09:59
    don't have a lot of time to get into the
  • 00:10:01
    the microbiota component in today but
  • 00:10:04
    there is quite a quite a bit of
  • 00:10:06
    information on how they influence both
  • 00:10:10
    beneficially and potentially negatively
  • 00:10:12
    the gut barrier function so as you look
  • 00:10:17
    at this image and this actually is a
  • 00:10:19
    graphic from the book itself to show
  • 00:10:21
    sort of the basic features of on the
  • 00:10:24
    left-hand side the small intestinal gut
  • 00:10:27
    barrier and on the right hand side the
  • 00:10:29
    colon got there you can see some some
  • 00:10:32
    differences the small intestines are
  • 00:10:35
    notably more have a greater surface area
  • 00:10:38
    with much larger villi the design mostly
  • 00:10:42
    to bring in more nutrients so we have
  • 00:10:46
    both Crypt and villi in small intestine
  • 00:10:48
    where as you can see in the colon we
  • 00:10:51
    mostly have crypts but not really many
  • 00:10:53
    villi the other major difference between
  • 00:10:56
    the two is on the left hand side you'll
  • 00:10:58
    see a single layer of mucus which is
  • 00:11:00
    kind of fragmented which is sort of the
  • 00:11:02
    gray so it looks like bricks they're
  • 00:11:05
    fragmented mucus because we
  • 00:11:08
    we need to have more access to the cells
  • 00:11:11
    in the small intestine where in the
  • 00:11:14
    large intestine we have two layers of
  • 00:11:16
    mucous a inner layer of mucous which is
  • 00:11:18
    very viscous and very difficult for
  • 00:11:21
    bacteria to penetrate an outer mucous
  • 00:11:24
    layer which is less viscous which is a
  • 00:11:26
    little more easy to penetrate for
  • 00:11:28
    bacteria and then the gut lumen where
  • 00:11:30
    you have most of the bacteria in the
  • 00:11:34
    colon and there's a very definite
  • 00:11:37
    difference between these two the small
  • 00:11:39
    intestine is designed as an interface
  • 00:11:41
    that is very absorptive and needs a lot
  • 00:11:45
    of interaction with the immune system
  • 00:11:47
    and with nutrient absorption whereas the
  • 00:11:51
    colon there is some interaction
  • 00:11:53
    obviously with the immune system much
  • 00:11:55
    less absorption and it really acts
  • 00:11:57
    primarily or in some cases primarily as
  • 00:12:01
    a fermentation for the the ecosystem the
  • 00:12:05
    microbiome that's there so there's quite
  • 00:12:08
    a bit of a different function and
  • 00:12:09
    therefore you're not surprised to see a
  • 00:12:11
    different sort of feature of the barrier
  • 00:12:14
    itself so let's just talk about some of
  • 00:12:16
    the cells that make up the barrier stem
  • 00:12:19
    cells are very important they sit at the
  • 00:12:22
    at the Nexus of the crypt and they're
  • 00:12:26
    essentially there to produce almost
  • 00:12:28
    every other cell type here so so they
  • 00:12:30
    are dividing and as the cells are moving
  • 00:12:33
    up the villi they are not only dividing
  • 00:12:36
    they're differentiating they're
  • 00:12:37
    differentiating into goblet cells that
  • 00:12:39
    produce mucus or some of the internal
  • 00:12:41
    endocrine cells that produce some of the
  • 00:12:43
    hormones or the absorptive cells in the
  • 00:12:45
    case of the entero sites the ability you
  • 00:12:47
    know to produce enzymes and/or
  • 00:12:49
    transporters so you have these going up
  • 00:12:53
    the villi and every 24 to 36 hours
  • 00:12:56
    you're seeing these cells turn over they
  • 00:13:00
    move up into out of the crypt into the
  • 00:13:02
    villi and they're being shed every 36 to
  • 00:13:05
    48 hours and so this is a Cantus is why
  • 00:13:07
    the the entero sites and the gut needs
  • 00:13:11
    so much energy and they need so many
  • 00:13:13
    building blocks is because it's a
  • 00:13:15
    constant turnover constant turnover and
  • 00:13:17
    as you can imagine every time a cell is
  • 00:13:19
    formed there needs to be a new
  • 00:13:21
    of tight junctions formed and so that's
  • 00:13:23
    why tight junction proteins become so
  • 00:13:25
    important as you as you is you're
  • 00:13:29
    producing these cells you have to
  • 00:13:30
    obviously produce the cells and their
  • 00:13:32
    connectivity to the other cells now this
  • 00:13:34
    is just showing this in two dimension
  • 00:13:36
    obviously it's in three dimensions so
  • 00:13:38
    it's actually going really always you
  • 00:13:40
    know towards you and away from you at
  • 00:13:42
    the same time the other cell type that
  • 00:13:44
    we have here is the Panem cell which are
  • 00:13:46
    shown on the right-hand side in green
  • 00:13:48
    and in the left hand side in yellow and
  • 00:13:50
    these actually go into the Crypt and
  • 00:13:53
    they produce quite a few of the
  • 00:13:56
    antimicrobial components that that are
  • 00:13:59
    there in the crypts because the Crypt is
  • 00:14:01
    a very protected space as it turns out
  • 00:14:04
    the Paneth cells I'll mention here in a
  • 00:14:07
    minute are also important for
  • 00:14:09
    maintaining stem cell function itself so
  • 00:14:12
    we have really from these stem cells we
  • 00:14:16
    make all of these different sort of
  • 00:14:18
    specialized cells so we know quite a bit
  • 00:14:21
    about the absorptive epithelial cells
  • 00:14:23
    I'm not going to spend a lot of time
  • 00:14:24
    talking about the details I'm going to
  • 00:14:27
    mention a few things about them but
  • 00:14:28
    they're located obviously primarily in
  • 00:14:31
    the duodenum and the ileum and jejunum
  • 00:14:36
    and we have a lot of these the ability
  • 00:14:38
    to move a lot of nutrients through the
  • 00:14:41
    transcellular route in a controlled
  • 00:14:44
    fashion to protect these cells obviously
  • 00:14:49
    the tight junctions become important so
  • 00:14:51
    I'm going to spend a little bit of time
  • 00:14:52
    explaining the tight junctions for those
  • 00:14:55
    of you who aren't as familiar with the
  • 00:14:57
    the proteins that are involved on the
  • 00:14:59
    left-hand side you can see this this
  • 00:15:02
    picture that gives you a better
  • 00:15:04
    understanding of what the tight
  • 00:15:06
    junctions are therefore they don't
  • 00:15:08
    actually close off the cell to cell
  • 00:15:10
    junction completely they actually end up
  • 00:15:12
    creating these very small pores which
  • 00:15:15
    allow water and a few small electrolytes
  • 00:15:18
    to get through and they're not just a
  • 00:15:20
    single connection you can see there it's
  • 00:15:23
    almost like a series of Ziploc if you
  • 00:15:26
    can imagine a series of Ziploc closures
  • 00:15:29
    with tiny little holes to allow water
  • 00:15:32
    and electrolytes through that's what
  • 00:15:33
    it's supposed to create
  • 00:15:35
    and it's usually up on the surface the
  • 00:15:39
    luminal surface you'll see most of the
  • 00:15:40
    tight junctions on the right-hand side
  • 00:15:42
    you can see that it's basically created
  • 00:15:45
    by these proteins that act as little
  • 00:15:48
    almost like velcro on one side you have
  • 00:15:50
    the clawed ins and including on the
  • 00:15:52
    other side you have other clods and
  • 00:15:53
    inclusions and other proteins that are
  • 00:15:56
    connected and they essentially can can
  • 00:15:59
    overlap one another and create this this
  • 00:16:01
    dynamic Junction and they're connected
  • 00:16:07
    on the inside to what we call 0 1 you
  • 00:16:10
    can see zone Yola occlude ins these are
  • 00:16:12
    these are types of proteins that connect
  • 00:16:15
    these these claudin and occlusions
  • 00:16:18
    together and they are in turn connected
  • 00:16:21
    to myosin and actin fibers and so what
  • 00:16:26
    happens is they are all sitting is if
  • 00:16:29
    you can imagine sitting together like a
  • 00:16:31
    like a Velcro connected to let's say
  • 00:16:34
    wires or rubber bands that if those are
  • 00:16:38
    pulled back then you can get an opening
  • 00:16:41
    of the tight Junction so instead of
  • 00:16:42
    having small aqueous pores you end up
  • 00:16:44
    having much larger pores and one of the
  • 00:16:47
    ways that that happens is a kinase
  • 00:16:49
    reaction or phosphorylation reaction
  • 00:16:51
    that's driven by something called myosin
  • 00:16:53
    light-chain kinase and ml c KS it's
  • 00:16:56
    referred to here and when that kind of
  • 00:16:59
    when that activity phosphorylates the
  • 00:17:01
    myosin chain it it contracts and pulls
  • 00:17:04
    back and opens up these these junctions
  • 00:17:08
    and that can that one of the main ways
  • 00:17:10
    that happens is inflammation
  • 00:17:12
    there's several inflammatory cascades
  • 00:17:14
    which will cause these to open up and
  • 00:17:17
    we're going to talk a little bit about
  • 00:17:18
    later about how we see that with lasagne
  • 00:17:23
    'ln and maybe ask the question about why
  • 00:17:26
    why does the do these cells have the
  • 00:17:28
    ability to do this if this was never
  • 00:17:30
    intended to be opened up why is there a
  • 00:17:32
    mechanism by which kinase can in this
  • 00:17:35
    case inflammation actually open this up
  • 00:17:37
    what seems like intentionally and most
  • 00:17:39
    people believe it's to give the immune
  • 00:17:42
    system more direct access to the lumen
  • 00:17:43
    unfortunately the reverse also is true
  • 00:17:46
    the lumen has more access to the immunes
  • 00:17:49
    so digestion of an absorption occurs
  • 00:17:52
    mostly in in the upper GI and we have
  • 00:17:56
    very specific places where absorption of
  • 00:17:59
    certain nutrients occurs one of the
  • 00:18:02
    things that's very important is that to
  • 00:18:05
    understand that it's a little bit
  • 00:18:06
    difficult to seem perhaps in a slide but
  • 00:18:08
    disaccharide ace is the enzymes that
  • 00:18:11
    break down maltose into its glucose
  • 00:18:14
    components or lactose into its
  • 00:18:16
    monosaccharides are located on the brush
  • 00:18:19
    border they're actually located not in
  • 00:18:21
    the lumen but they're actually located
  • 00:18:23
    on the cell surface and that occurs when
  • 00:18:27
    you have healthy and taro sites however
  • 00:18:29
    if you have an inflamed individual and
  • 00:18:33
    they they have villous atrophy and they
  • 00:18:35
    lose the number of cells that they would
  • 00:18:37
    have otherwise otherwise be there you
  • 00:18:40
    actually reduce the capacity then to
  • 00:18:43
    digest disaccharides you don't lose it
  • 00:18:46
    completely but you reduce that capacity
  • 00:18:49
    so you oftentimes will see people who
  • 00:18:51
    become lactose intolerant or intolerant
  • 00:18:54
    to other disaccharides as a secondary
  • 00:18:57
    effect to other inflammatory GI
  • 00:19:01
    conditions because you've lost some of
  • 00:19:03
    the benefit of the capacity of these
  • 00:19:05
    disaccharide aces you also as you can
  • 00:19:08
    see in the lower picture there you have
  • 00:19:10
    a number of enzymes that that take small
  • 00:19:14
    polypeptides and break them down into
  • 00:19:16
    amino acids and so and you have a number
  • 00:19:19
    of transporters as well so you'll also
  • 00:19:21
    perhaps have the inability to break down
  • 00:19:24
    certain small peptides and also then
  • 00:19:27
    drive potentially other immunological
  • 00:19:29
    reactions that will be secondary to
  • 00:19:32
    inflammatory conditions so it's really
  • 00:19:34
    important to understand that the entero
  • 00:19:36
    sites are not just there to absorb
  • 00:19:38
    nutrients sort of passively
  • 00:19:40
    that the transporters and the enzymes
  • 00:19:43
    that are involved are highly important
  • 00:19:45
    for especially in this case macro
  • 00:19:47
    nutrient absorption lipids are a little
  • 00:19:49
    different so they don't require enzymes
  • 00:19:51
    per se from from entero sites but
  • 00:19:54
    certainly disaccharides and small
  • 00:19:56
    polypeptides and so this becomes a very
  • 00:19:59
    important component
  • 00:20:01
    so again let's run through a few of
  • 00:20:04
    these others Paneth cells you know again
  • 00:20:07
    found only in the small intestines found
  • 00:20:10
    primarily in the ileum they migrate into
  • 00:20:12
    the Crypt after differentiation from
  • 00:20:14
    stem cells so they move down rather than
  • 00:20:16
    up and they are the primary secrete errs
  • 00:20:19
    of antimicrobial peptides in the gut
  • 00:20:21
    movement and so there's a different sort
  • 00:20:24
    of cells they're actually a few other
  • 00:20:25
    cells and parasites themselves actually
  • 00:20:27
    can produce some antimicrobial peptides
  • 00:20:29
    but in this case the pan of cells are
  • 00:20:32
    there they're very long-lived so they
  • 00:20:34
    don't turn over nearly as fast as those
  • 00:20:37
    that are migrating upward and then they
  • 00:20:40
    specifically help regulate the stem cell
  • 00:20:42
    activity so they're highly regulatory
  • 00:20:45
    and that's why it's important that they
  • 00:20:47
    function in the crypt in our you know so
  • 00:20:50
    vulnerable to other other stressors in
  • 00:20:54
    the GI lumen the immune system is
  • 00:20:57
    tightly bound to the GI to the GI cells
  • 00:21:02
    on the left hand side you can see
  • 00:21:03
    generally where you have these peyer's
  • 00:21:05
    patches and I've shown also that you
  • 00:21:08
    have epithelial cells these
  • 00:21:11
    intraepithelial lymphocytes on both
  • 00:21:13
    sides they're in blue and essentially
  • 00:21:15
    they tuck themselves in about every 10
  • 00:21:19
    to 15 cells they are there and so you
  • 00:21:23
    see about you see them interspersed all
  • 00:21:25
    throughout and essentially these are
  • 00:21:27
    very unique kinds of T cells and they
  • 00:21:32
    slightly different because they're more
  • 00:21:34
    regulatory type T cells rather than
  • 00:21:36
    affect their type T cells and they're
  • 00:21:38
    there to continually sense what's going
  • 00:21:40
    on dendritic cells are able to put their
  • 00:21:43
    arm all the way through into the gut
  • 00:21:46
    lumen and begin sampling what's going on
  • 00:21:48
    dendritic cells are really the
  • 00:21:49
    organizers of the immune system within
  • 00:21:52
    the gut and then on the left hand side
  • 00:21:54
    of the of the right picture where you
  • 00:21:57
    see these M cells M cells are called
  • 00:21:59
    micro fold cells these are special kinds
  • 00:22:02
    of Antero sites designed specifically to
  • 00:22:05
    allow antigens to come across and be
  • 00:22:08
    available in a controlled environment to
  • 00:22:11
    both dendritic cells and mostly T cells
  • 00:22:15
    so we have T and B cells and dendritic
  • 00:22:17
    cells who are that are all sitting there
  • 00:22:19
    sampling constantly sampling what is
  • 00:22:22
    available to it in the gut lumen this is
  • 00:22:25
    mostly occurring in the small intestines
  • 00:22:27
    where you have much more accessibility
  • 00:22:29
    to the M cells you have very little of
  • 00:22:33
    this going on in the colon so again the
  • 00:22:39
    colon is designed to be let's say more
  • 00:22:42
    of a barrier than the interface
  • 00:22:44
    functions of the small intestine so
  • 00:22:46
    there's two layers of mucus as we
  • 00:22:47
    mentioned there's an increased number of
  • 00:22:49
    goblet cells because they're the ones
  • 00:22:51
    producing mucin there's like I said less
  • 00:22:54
    interface more barrier much purer or a
  • 00:22:57
    much lower concentration of immune cells
  • 00:22:59
    we have what we call colon patches
  • 00:23:01
    rather than peyer's patches they're much
  • 00:23:04
    fewer and and much less concentrated in
  • 00:23:07
    their ability to function but obviously
  • 00:23:09
    they're they're there because you do
  • 00:23:11
    have breaches in the colon as well
  • 00:23:13
    there's fewer enter endocrine cells so
  • 00:23:16
    there's less cells that are signaling
  • 00:23:18
    because there's just less of that going
  • 00:23:21
    on here because you have really more of
  • 00:23:23
    a large capacity for fermentation so you
  • 00:23:27
    have really a controlled fermenting
  • 00:23:29
    environment rather than a in a
  • 00:23:32
    controlled interface environment and one
  • 00:23:37
    of the ways that that's controlled and I
  • 00:23:40
    talked quite a bit about this in the
  • 00:23:41
    book in our microbiota or microbiome
  • 00:23:44
    chapter is the idea that especially in
  • 00:23:47
    in the colon you have these different
  • 00:23:49
    layers the lumen which is which is has a
  • 00:23:53
    large amount of bacteria and you have
  • 00:23:58
    some that are that penetrate into the
  • 00:24:00
    outer mucous layer and very few these
  • 00:24:02
    are usually flagellated bacteria or
  • 00:24:05
    those that have very special
  • 00:24:06
    characteristics that are able to get all
  • 00:24:08
    the way down into the inner mucous layer
  • 00:24:10
    of the colon and this is controlled by a
  • 00:24:12
    number of different factors I speak
  • 00:24:15
    about in the book quite a bit about the
  • 00:24:16
    different mutants that make up both a
  • 00:24:19
    firm and the loose mucus in the in the
  • 00:24:24
    gut there are certain bacteria that
  • 00:24:26
    actually are intended or embed
  • 00:24:29
    themselves into the mucus Aquaman Jie
  • 00:24:32
    mucin Ophelia is one classic example
  • 00:24:34
    where we have a good commensal organism
  • 00:24:36
    that embeds itself in the mucus there's
  • 00:24:39
    different shear gradients so obviously
  • 00:24:42
    as the contents of the gut lumen are
  • 00:24:45
    moving of different shear forces which
  • 00:24:47
    affect which bacteria can survive
  • 00:24:49
    different oxygen gradients also affect
  • 00:24:53
    the ability for different bacteria to
  • 00:24:55
    survive in different areas of the gut
  • 00:24:57
    the availability of host defense
  • 00:25:00
    molecules the concentration of those the
  • 00:25:03
    ability for the immune system to produce
  • 00:25:04
    specific secretory IgA etc etc and as we
  • 00:25:10
    mentioned the change in nutrient in
  • 00:25:12
    within the mucus with what akka mancilla
  • 00:25:15
    and then the the cripton niche which is
  • 00:25:17
    extremely extremely special and needs to
  • 00:25:21
    be protected and so like it's shown here
  • 00:25:23
    only a few bacteria ever make it down
  • 00:25:25
    into that and there's a lot of data on
  • 00:25:29
    you know looking at you have to
  • 00:25:31
    obviously do this by biopsy to look at
  • 00:25:34
    different areas not only longitudinally
  • 00:25:36
    along the gut but then you know
  • 00:25:39
    sequentially or cross-sectionally across
  • 00:25:41
    the gut you have different microbiota
  • 00:25:44
    and all these different areas and all of
  • 00:25:47
    those are influencing the gut barrier
  • 00:25:49
    itself so breaking the gut barrier and
  • 00:25:54
    so the term leaky gut isn't as many of
  • 00:25:56
    you know is becoming I guess in some
  • 00:25:58
    ways more popular I showed on the right
  • 00:26:00
    hand side I did this briefly looked at
  • 00:26:04
    leaky gut on PubMed over the last well
  • 00:26:07
    since 1984 and you can see while it has
  • 00:26:10
    grown quite a bit in the last four or
  • 00:26:12
    five years we still don't have that many
  • 00:26:14
    hits per year I mean that the highest we
  • 00:26:17
    have is 26 hits in the last three years
  • 00:26:20
    and you know it really in night in 2010
  • 00:26:24
    2011 it just exceeded 10 so this term is
  • 00:26:28
    still not used that often and I pulled
  • 00:26:31
    this from WebMD I thought it was kind of
  • 00:26:33
    interesting
  • 00:26:34
    it says here from an MD standpoint it's
  • 00:26:36
    a very gray area says gee I guess our
  • 00:26:39
    neurologist
  • 00:26:40
    Donald Kirby
  • 00:26:42
    physicians don't know enough about the
  • 00:26:44
    gut which is our biggest immune system
  • 00:26:45
    Oregon leaky gut syndrome isn't a
  • 00:26:47
    diagnosis taught in medical school
  • 00:26:49
    instead
  • 00:26:50
    leaky gut really means you've got a
  • 00:26:52
    diagnosis that still needs be made you
  • 00:26:54
    hope that your doctor is good and enough
  • 00:26:56
    Sherlock Holmes but sometimes it's very
  • 00:26:58
    hard to make a diagnosis we don't know a
  • 00:27:00
    lot but we know that it exists says
  • 00:27:03
    Linda Lee from Johns Hopkins in the
  • 00:27:06
    absence of evidence we don't know what
  • 00:27:07
    it means or what therapies can directly
  • 00:27:09
    address it so as you know if you get a
  • 00:27:12
    hold of a book you realize I do like the
  • 00:27:15
    term intestinal permeability a little
  • 00:27:17
    more because and maybe other specific
  • 00:27:21
    terms but certainly leaky gut is is a
  • 00:27:23
    term that has unlike other terms maybe
  • 00:27:27
    is growing a little bit and people are a
  • 00:27:29
    little more comfortable with it as as we
  • 00:27:31
    know more about it here's a couple
  • 00:27:34
    papers just came out in last couple
  • 00:27:35
    years to kind of give you an idea leaky
  • 00:27:37
    gut is a danger signal for autoimmune
  • 00:27:39
    disease and on the right hand side
  • 00:27:41
    elevated fecal calprotectin in patients
  • 00:27:44
    with Alzheimer's dementia indicates
  • 00:27:45
    leaky gut so we're starting to see you
  • 00:27:48
    know other people use this in different
  • 00:27:49
    terms so it's a term that still is some
  • 00:27:53
    controversy behind it anyway one of the
  • 00:27:56
    reasons is is is because some people
  • 00:27:58
    view leaky gut as only this extreme view
  • 00:28:02
    and essentially what we mean by that
  • 00:28:04
    extreme view is a viewer basically you
  • 00:28:06
    know whole organisms are getting in past
  • 00:28:09
    the gut because there's the complete
  • 00:28:11
    breach of the barrier and we measure
  • 00:28:13
    this by you know septic sepsis or
  • 00:28:16
    systemic infections or you know little
  • 00:28:21
    polysaccharides or some you know
  • 00:28:22
    endotoxin iya kind of thing rather than
  • 00:28:25
    perhaps a more subtle of you that we're
  • 00:28:28
    seeing where we're just seeing small
  • 00:28:31
    immuno genic agents getting through or
  • 00:28:33
    alterations in the immune function
  • 00:28:35
    caused by changes in tight Junction
  • 00:28:38
    function so we know that there's various
  • 00:28:42
    ranges of what leaky gut can mean if you
  • 00:28:45
    look at a more common scenario here
  • 00:28:47
    where I'm showing some sort of
  • 00:28:50
    inflammation you can see at the top this
  • 00:28:52
    MLC is the is the myosin light-chain
  • 00:28:56
    that is phosphorylating the myosin
  • 00:28:58
    light-chain which is then pulling back
  • 00:29:00
    our occlusions and claude ins and
  • 00:29:02
    pulling back and opening up you can see
  • 00:29:06
    you can open up this the tight Junction
  • 00:29:09
    creating this intestinal permeability
  • 00:29:10
    and there's many different things that
  • 00:29:13
    can do that and of course gliadin or
  • 00:29:16
    gluten is sort of become the one of the
  • 00:29:19
    quintessential ways to look at this from
  • 00:29:21
    Sonia Lin and we'll look at that briefly
  • 00:29:24
    here so as many of you know
  • 00:29:28
    Eliseo pizanno did a number of you know
  • 00:29:33
    whole range of research in this area
  • 00:29:36
    looking specifically for cholera a
  • 00:29:40
    cholera toxin molecule actually and came
  • 00:29:45
    across a molecule that he end up coining
  • 00:29:49
    is on Ewan we also know that it's it
  • 00:29:52
    actually as part of another molecule but
  • 00:29:54
    Sanyal and became the name that he gave
  • 00:29:57
    to it and it he was he expanded this
  • 00:30:00
    story looking at the role of Zhan Ewan
  • 00:30:03
    and gland gluten or gladden as a trigger
  • 00:30:06
    for the whole leaky gut or intestinal
  • 00:30:10
    permeability component for those who
  • 00:30:12
    aren't as familiar with the story
  • 00:30:14
    essentially and we don't have time to
  • 00:30:16
    get into this in in detail today but
  • 00:30:19
    essentially what happens in it basically
  • 00:30:21
    from this picture from left to right up
  • 00:30:23
    at the top it's showing gluten or
  • 00:30:25
    gliadin a protein or peptide binding to
  • 00:30:29
    a protein on the cell surface the CXC
  • 00:30:33
    are three receptor and that triggers in
  • 00:30:36
    those cells or in some of those cells
  • 00:30:38
    depending on their genetics a high
  • 00:30:40
    amount of azan Ewan as on Yulin is again
  • 00:30:43
    this protein still a question about why
  • 00:30:45
    we produce this protein it's called pre
  • 00:30:48
    haptic labelling so maybe it has another
  • 00:30:50
    function in in the body but as on Yulin
  • 00:30:53
    is produced and secreted it can bind to
  • 00:30:56
    the cell surface of enterocyte and as it
  • 00:31:00
    binds to the cell surface it then
  • 00:31:03
    triggers myosin light-chain kinase which
  • 00:31:06
    then pulls back the the tight junctions
  • 00:31:10
    pulls back as I meal including one which
  • 00:31:12
    then pulls on occluding and Clawdeen's
  • 00:31:15
    and opens up this this disjunction and
  • 00:31:20
    you can see here obviously this allows
  • 00:31:23
    peptides in this case it's showing
  • 00:31:24
    gluten or gliadin peptides coming in and
  • 00:31:27
    binding to the T cells and creating in
  • 00:31:29
    certain individuals the the whole celiac
  • 00:31:32
    phenomenon and perhaps and other people
  • 00:31:34
    non celiac in you know gluten
  • 00:31:38
    sensitivity and all of that going on is
  • 00:31:41
    the question is why does the body have a
  • 00:31:43
    system why are these cells have a system
  • 00:31:45
    that allows the tight Junction to open
  • 00:31:48
    up and so many people are speculating
  • 00:31:49
    that in certain instances the body
  • 00:31:52
    actually creates a triggering signal
  • 00:31:54
    perhaps from certain peptides or
  • 00:31:56
    bacteria that triggers the opening of
  • 00:32:00
    the tight Junction intending for the
  • 00:32:02
    immune system to have greater access to
  • 00:32:04
    the gut moment in order to protect
  • 00:32:07
    itself however perhaps in an
  • 00:32:10
    overabundance of certain peptides like
  • 00:32:13
    gluten that this backfires and we end up
  • 00:32:16
    having too much activity too much immune
  • 00:32:19
    interaction with the gut lumen creating
  • 00:32:21
    the autoimmune cascade that we see with
  • 00:32:24
    with celiac but also other related
  • 00:32:27
    autoimmune diseases that may be
  • 00:32:29
    triggered so how do we measure this how
  • 00:32:32
    do we measure the permeability so
  • 00:32:35
    there's a number of different ways to do
  • 00:32:37
    this the gold standard is actually to do
  • 00:32:39
    an ex vivo biopsy of the gut cells and
  • 00:32:45
    you place them in what's called an icing
  • 00:32:47
    chamber and this picture on the
  • 00:32:48
    left-hand side essentially shows it only
  • 00:32:51
    shows one single cell but it would
  • 00:32:52
    imagine there's a series of cells all
  • 00:32:55
    oriented with the with the Lu little
  • 00:32:57
    side on one side so you have all of them
  • 00:33:00
    oriented the same way and now you can
  • 00:33:02
    measure their ability to allow in this
  • 00:33:06
    case it's showing chloride ions but you
  • 00:33:08
    can Ahmet Bey Salim Escher the trans
  • 00:33:10
    epithelial electrical resistance so you
  • 00:33:12
    can measure how easy can we get this
  • 00:33:16
    barrier to allow electrical resistance
  • 00:33:19
    and so if it if there's no resistance
  • 00:33:22
    obviously it means
  • 00:33:23
    that there's that we have a breach in
  • 00:33:27
    the barrier we have a very poor barrier
  • 00:33:29
    function and so this became sort of the
  • 00:33:31
    gold standard in not only can you do
  • 00:33:34
    this with biopsies you can actually just
  • 00:33:36
    grow cells along a nussing chamber and
  • 00:33:39
    then you can test you know botanical as
  • 00:33:42
    you can test other noxious agents and
  • 00:33:45
    see how they affect the gut barrier so a
  • 00:33:47
    lot of the data that that we know about
  • 00:33:50
    certain agents that either improve or
  • 00:33:54
    decreased gut barrier function occurs in
  • 00:33:57
    ex vivo icing chamber type reactions so
  • 00:34:01
    it's something that that you want to
  • 00:34:02
    keep in mind when you look at the
  • 00:34:04
    research we have less in vivo ways to do
  • 00:34:07
    this so one in vivo measure that is I
  • 00:34:09
    think generally thought of as as the
  • 00:34:11
    best currently is the size exclusion
  • 00:34:14
    test which is the typically thought of
  • 00:34:17
    as the lactulose mannitol test it's
  • 00:34:19
    probably the most common and essentially
  • 00:34:21
    this allows you to put different size
  • 00:34:24
    carbohydrates in this in the system
  • 00:34:26
    lactulose and mannitol
  • 00:34:28
    whereas mannitol should be able to get
  • 00:34:30
    through the cell surface through the
  • 00:34:33
    normal trans epithelial pathway gives
  • 00:34:38
    you sort of a big picture of what is the
  • 00:34:41
    denominator what is the gut area and
  • 00:34:43
    lactulose should not be able to get
  • 00:34:46
    easily across unless it's going through
  • 00:34:48
    between the cells so if you have
  • 00:34:50
    lactulose in your urine or a high level
  • 00:34:53
    of lactose it means you're getting more
  • 00:34:55
    and more of that through between the
  • 00:34:58
    cells so this lecture list of mannitol
  • 00:35:00
    tests becomes a general ratio that
  • 00:35:04
    allows you to give an idea of you know
  • 00:35:06
    what is the ratio between sort of the
  • 00:35:08
    overall surface of the gut and the
  • 00:35:10
    ability for lactose to get through a
  • 00:35:11
    pair of cellular manner there's a few
  • 00:35:13
    others that are used as well but the
  • 00:35:16
    lactose mannitol is probably the most
  • 00:35:17
    common so other tests that are available
  • 00:35:22
    or thought to have an effect I've got
  • 00:35:24
    permeability urine or serum levels for
  • 00:35:27
    microbial metabolites endotoxin d
  • 00:35:30
    lactate are often can be used increased
  • 00:35:34
    levels of bacteria and the dense mucus
  • 00:35:36
    that you actually can biopsy
  • 00:35:37
    the dense mucus and show that the more
  • 00:35:40
    bacteria in the dense mucus of the colon
  • 00:35:43
    the more likely you are to have a
  • 00:35:46
    intestinal permeability reduced plasma
  • 00:35:49
    citrulline as a biomarker of glutamine
  • 00:35:52
    fecal calprotectin as we've seen has
  • 00:35:54
    also been shown to be connected with
  • 00:35:56
    that it's mostly obviously an
  • 00:35:57
    inflammatory marker but very linked to
  • 00:36:01
    to get permeability and you can also
  • 00:36:05
    measure Sanyal in claudin occluding and
  • 00:36:08
    to look at tight Junction proteins these
  • 00:36:10
    are often done ex vivo but you can also
  • 00:36:12
    look at these and there's some data
  • 00:36:15
    suggesting that and then serum and maybe
  • 00:36:18
    fecal asan Yulin is also being used
  • 00:36:20
    quite readily
  • 00:36:21
    now as a marker of intestinal
  • 00:36:24
    permeability or
  • 00:36:25
    I should probably say a marker of gut
  • 00:36:28
    barrier function which is which may or
  • 00:36:30
    may not result always in intestinal
  • 00:36:33
    permeability per se so we know that
  • 00:36:35
    there are many conditions any condition
  • 00:36:36
    where you're putting stress on the gut
  • 00:36:39
    in an inflammatory stress we know less
  • 00:36:43
    about for instance things like IBS there
  • 00:36:46
    are some studies that show IBS with
  • 00:36:48
    diarrhea is statistically connected with
  • 00:36:51
    changes in gut barrier function although
  • 00:36:54
    in other cases it's not probably because
  • 00:36:57
    IBS definition is not always as clear in
  • 00:36:59
    different cohorts and then there's some
  • 00:37:03
    question about SIBO whether SIBO as a
  • 00:37:06
    diagnosis is connected with changes in
  • 00:37:10
    barrier function what we do know is
  • 00:37:12
    there's a growing amount of research
  • 00:37:13
    suggesting that obese subjects are have
  • 00:37:17
    more and more intestinal permeability
  • 00:37:20
    there's a number of different studies
  • 00:37:21
    now looking at this looking at in this
  • 00:37:24
    case serum Sanyal levels go up in in
  • 00:37:26
    most cases with obesity and insulin
  • 00:37:28
    resistance so something that that were
  • 00:37:30
    obviously is a growing problem and
  • 00:37:33
    should be looked at in those subjects
  • 00:37:36
    one of the issues we have in looking at
  • 00:37:39
    the data on preventing and treating is
  • 00:37:42
    that intestinal permeability is often
  • 00:37:44
    not measured like I said there's some of
  • 00:37:46
    these studies that look at uh Singh
  • 00:37:47
    chambers but very few human clinical
  • 00:37:49
    trials at
  • 00:37:51
    look at this so you started looking in
  • 00:37:53
    the literature and say will there data
  • 00:37:55
    on dietary interventions and changing
  • 00:37:57
    that permeability levels well there
  • 00:38:00
    actually are very few I actually found
  • 00:38:02
    this one that showed when they actually
  • 00:38:05
    gave now you may not like this but they
  • 00:38:08
    give pasta you know a wheat product but
  • 00:38:11
    they gave them a five-week crossover
  • 00:38:13
    study looking at healthy young
  • 00:38:15
    individuals giving them 800 grams of
  • 00:38:17
    pasta with and without inulin which is a
  • 00:38:19
    prebiotic that stimulates bacteria tip
  • 00:38:23
    typically and you can see they saw a
  • 00:38:25
    statistical change in just five weeks a
  • 00:38:29
    statistical reduction in lactulose
  • 00:38:31
    mannitol a reduction in serum Sanyal in
  • 00:38:33
    and a slight increase in glp-1 which is
  • 00:38:36
    which is an an endocrine component in
  • 00:38:40
    the gut so again very few I mean I wish
  • 00:38:43
    I had a hundred papers to show you but
  • 00:38:45
    there are very few like this kind of
  • 00:38:48
    study and this was just done just a few
  • 00:38:49
    years ago if you look in the data and
  • 00:38:51
    say how about micronutrients vitamins
  • 00:38:53
    minerals all the things that we we think
  • 00:38:54
    are good for the gut we have very very
  • 00:38:56
    limited data especially in what I call
  • 00:38:59
    healthy or relatively healthy Westerners
  • 00:39:01
    most of these are done in either very
  • 00:39:06
    sick children or in people that exercise
  • 00:39:10
    intensively and see a drop in gut
  • 00:39:12
    permeability or increase I should say
  • 00:39:15
    and gut permeability and a decrease in
  • 00:39:17
    immune function so one of those that we
  • 00:39:20
    often think about quite often is
  • 00:39:21
    glutamine which we're you know for as
  • 00:39:23
    many years as I've heard about glutamine
  • 00:39:25
    you'd think there'd be hundreds and
  • 00:39:26
    hundreds of studies on the role of
  • 00:39:28
    glutamine and barrier function and it
  • 00:39:29
    turns out very few most of these are on
  • 00:39:33
    burn or a severe injury patients it's
  • 00:39:37
    frequently used with you know I mean I
  • 00:39:39
    think probably many people that are
  • 00:39:41
    listening to this would say you know
  • 00:39:42
    they've gotten great results using
  • 00:39:44
    glutamine but the research on it is very
  • 00:39:47
    very limited when you look at animal
  • 00:39:50
    studies and cell culture studies there's
  • 00:39:52
    a whole list of things I'm not going to
  • 00:39:53
    go down this list you have the slide but
  • 00:39:55
    there are numerous explanations for why
  • 00:39:57
    we think glutamine would affect
  • 00:39:59
    intestinal barrier function it improves
  • 00:40:02
    almost everything we want to look at
  • 00:40:04
    this is a great recent review published
  • 00:40:07
    this year on the role of glutamine
  • 00:40:08
    intestines and its implications and
  • 00:40:10
    intestinal diseases I would recommend
  • 00:40:12
    that you get it but you can see you know
  • 00:40:14
    the standard sort of things that we
  • 00:40:16
    would think about all benefitting and
  • 00:40:18
    and and what we would assume maintaining
  • 00:40:21
    intestinal tissue integrity however like
  • 00:40:25
    I said we have very few studies in
  • 00:40:27
    humans this this study that I show you
  • 00:40:30
    here shows that they took these
  • 00:40:32
    Brazilian shantytown children that had
  • 00:40:34
    high levels of intestinal barrier or I
  • 00:40:37
    should say low levels of intestinal
  • 00:40:38
    barrier function and they will improve
  • 00:40:40
    thriving they were able to improve their
  • 00:40:43
    freighting but they actually didn't
  • 00:40:44
    really see much of a change and they
  • 00:40:47
    didn't really aim look at the the level
  • 00:40:51
    of intestinal permeability you can see
  • 00:40:53
    below here a meta-analysis on on
  • 00:40:55
    critically ill patients looking at
  • 00:40:58
    glutamine enriched enteral feeding so
  • 00:41:00
    these are studies that are not you know
  • 00:41:02
    the typical ones that you're seeing
  • 00:41:04
    here's a study where they actually
  • 00:41:05
    looked at patients with crohn's disease
  • 00:41:08
    and you can see they use both glutamine
  • 00:41:11
    and saw an improvement and in intestinal
  • 00:41:14
    permeability but look at the dose 40
  • 00:41:16
    grams of glutamine they gave them half a
  • 00:41:18
    gram for every kilogram of ideal body
  • 00:41:19
    weight so this is for an 80 kilogram
  • 00:41:22
    person at me for two grams of glutamine
  • 00:41:23
    so this is again an extreme sort of
  • 00:41:26
    situation a few others that we have in
  • 00:41:28
    the literature are during immune
  • 00:41:32
    function during heavy load training
  • 00:41:34
    given glutamine 10 grams a day you can
  • 00:41:36
    see that they were able to attenuate and
  • 00:41:38
    ten you ate the immuno suppression but
  • 00:41:41
    they didn't actually measure that
  • 00:41:42
    permeability so we can assume there was
  • 00:41:45
    some benefit but we don't know so I tend
  • 00:41:48
    to tell people that you know the dose
  • 00:41:51
    recommendation for a lot of clinicians
  • 00:41:52
    is somewhere in the four to eight grams
  • 00:41:54
    a day range which typically requires
  • 00:41:56
    this to be taken not in capsules but you
  • 00:41:58
    know in powders and again large
  • 00:42:02
    anecdotal data out data set out there
  • 00:42:04
    but very little clinical trials for me
  • 00:42:07
    to tell you exactly if you see you know
  • 00:42:10
    this intellectualist mannitol test and
  • 00:42:12
    you give this amount of glutamine you're
  • 00:42:14
    going to see this kind of change in this
  • 00:42:15
    amount of time we need more
  • 00:42:18
    and we and actually we need more people
  • 00:42:19
    publishing their data so that we can get
  • 00:42:22
    access to this information we know that
  • 00:42:25
    there's a lot of phytonutrients out
  • 00:42:27
    there that we I can't go through all of
  • 00:42:30
    them and I'm not going to try but
  • 00:42:32
    there's a number of them I typically
  • 00:42:34
    tell people phytonutrients should be
  • 00:42:38
    thought of as a way to diversify the
  • 00:42:41
    diet not that you're trying to get a
  • 00:42:43
    specific dose it's really better to
  • 00:42:45
    think of following a long-term low-dose
  • 00:42:49
    supplementation ie
  • 00:42:51
    good diversity in the in the fruits and
  • 00:42:54
    vegetables that you eat and or the
  • 00:42:56
    supplements that you can supplement with
  • 00:42:57
    the diversity of phytonutrients
  • 00:42:59
    berberine is one that's kind of come on
  • 00:43:01
    the scene which is interesting because
  • 00:43:02
    there's been some study and animal
  • 00:43:05
    suggesting that it can improve
  • 00:43:06
    intestinal barrier function and so we've
  • 00:43:10
    seen some of this data
  • 00:43:11
    improving tight junctions improving in
  • 00:43:15
    animal models both type 2 diabetic
  • 00:43:17
    animal models so we we see that effect
  • 00:43:19
    when it comes to humans as well here's a
  • 00:43:22
    study looking at IBS in humans looking
  • 00:43:26
    at changes in diarrhea given burring
  • 00:43:30
    burring hydrochloride you can see a
  • 00:43:32
    benefit on the left-hand side for the
  • 00:43:34
    change in urgent need for defecation
  • 00:43:35
    they gave this for eight weeks you can
  • 00:43:37
    see it continued down for eight weeks
  • 00:43:39
    and after they stopped it went back up
  • 00:43:40
    so whether or not this is related at all
  • 00:43:43
    to gut barrier function we don't know
  • 00:43:45
    because they didn't measure it and gut
  • 00:43:48
    permeability is not often measured in
  • 00:43:50
    some of these studies probiotics are
  • 00:43:53
    often thought to be beneficial again
  • 00:43:56
    they act good commensal organisms are
  • 00:43:58
    always acting to benefit the gut there's
  • 00:44:01
    a number of different studies that have
  • 00:44:02
    looked at in vitro these are in vitro
  • 00:44:04
    studies mostly looking at uh Seng
  • 00:44:07
    chamber type product of experiments and
  • 00:44:11
    you can see you know Bifidobacterium
  • 00:44:13
    bacteria lactobacillus plantarum bsl-3
  • 00:44:16
    which is a combination of eight
  • 00:44:18
    different bacteria bifida bacteria and
  • 00:44:20
    Santis and el acidophilus and at the
  • 00:44:22
    bottom you can see Saccharomyces
  • 00:44:24
    boulardii I believe that if you look
  • 00:44:26
    beyond these you'll see that most
  • 00:44:28
    lactobacilli at best little bacteria and
  • 00:44:30
    probably sacrum
  • 00:44:32
    anything that improves sort of the
  • 00:44:34
    status of the gut is likely to have some
  • 00:44:36
    sort of triggering effect on improving
  • 00:44:38
    the intestinal barrier function there
  • 00:44:40
    might be some exceptions to that but I
  • 00:44:41
    think that's mult going to be mostly
  • 00:44:43
    true a good gut microbiota is going to
  • 00:44:46
    improve gut barrier function we see a
  • 00:44:49
    few different studies this was actually
  • 00:44:51
    a meta-analysis looking at a number of
  • 00:44:53
    Chinese studies on patients going in
  • 00:44:57
    with colorectal cancer for operate a
  • 00:44:59
    firfer
  • 00:45:00
    for colorectal cancer operations and
  • 00:45:03
    they showed that they were able to
  • 00:45:05
    improve the lactulose to mannitol tests
  • 00:45:07
    with almost every probiotic strain and
  • 00:45:09
    dose they tried so again these are
  • 00:45:11
    somewhat low quality studies but kind of
  • 00:45:14
    gives you the idea that when you start
  • 00:45:16
    looking at this there seems to be some
  • 00:45:19
    improvement here was just one of the
  • 00:45:21
    studies looking at 160 subjects giving
  • 00:45:23
    probiotics and this was actually a
  • 00:45:25
    combination of plantarum acidophilus and
  • 00:45:28
    B long them and you can see that
  • 00:45:31
    post-operative serums on Yulin excuse me
  • 00:45:34
    if you look up in the upper left hand
  • 00:45:35
    corner you can see bacterial
  • 00:45:36
    translocation went down at the lower
  • 00:45:39
    left hand side you can see the the trans
  • 00:45:42
    epithelial resistance so this is a uh
  • 00:45:43
    Singh chambered study or test and you
  • 00:45:46
    can see that went up so it improved and
  • 00:45:48
    up in the right-hand corner you can see
  • 00:45:50
    lactulose and mannitol test went down
  • 00:45:53
    and the the transmitted coastal
  • 00:45:56
    permeation which means bacteria within
  • 00:45:59
    the the mucus went down so this was
  • 00:46:01
    again all the things that they measured
  • 00:46:03
    which you know wasn't
  • 00:46:04
    systemic but they all improved with
  • 00:46:07
    giving this blend of a probiotic here's
  • 00:46:11
    another study looking at probiotic
  • 00:46:14
    supplements we just think and contain
  • 00:46:16
    six different probiotics Bifidobacterium
  • 00:46:19
    lactobacillus etc and they looked at
  • 00:46:21
    fecal zaniel and levels in these
  • 00:46:23
    individuals and you can see fecal zhonya
  • 00:46:25
    limb levels to go down and again equals
  • 00:46:28
    on you and and maybe is not as
  • 00:46:30
    consistent as serums on you and as far
  • 00:46:32
    as predicting function of the gut but
  • 00:46:34
    nonetheless another study looking at
  • 00:46:36
    this Saccharomyces boulardii and this
  • 00:46:40
    set of Crohn's patients you can see a
  • 00:46:42
    very modest dose of sacrum I see blood
  • 00:46:45
    400 million CFU not even in the billions
  • 00:46:48
    given every eight hours of those so this
  • 00:46:50
    was given quite frequently and you can
  • 00:46:52
    see that given sacrifices Velarde these
  • 00:46:56
    Crohn's disease patients that we're
  • 00:46:58
    seeing they're lactose the mannitol
  • 00:47:00
    racial go up went down dramatically
  • 00:47:02
    after being given the sacrum Isis
  • 00:47:05
    Velarde so again these these studies are
  • 00:47:09
    very limited but they do suggest the
  • 00:47:12
    things that we've been talking about how
  • 00:47:14
    about colostrum is just just another
  • 00:47:16
    couple things colostrum has been shown
  • 00:47:18
    to look at this these are an athlete's
  • 00:47:20
    again and I if I can just give you one
  • 00:47:22
    from a lifestyle standpoint if you have
  • 00:47:24
    someone that has gut issues especially
  • 00:47:27
    if you think there's barrier issues and
  • 00:47:28
    immune related issues one of the ways
  • 00:47:31
    you can exacerbate that negatively is to
  • 00:47:33
    have them become you know these athletes
  • 00:47:36
    that strain and stress themselves so
  • 00:47:38
    these are again a classic way to improve
  • 00:47:41
    or to induce I should say intestinal
  • 00:47:44
    permeability and induce
  • 00:47:47
    immunosuppression is you know run a
  • 00:47:49
    marathon so they take a lot of these
  • 00:47:51
    individuals and they look at ways they
  • 00:47:53
    can improve that in this case colostrum
  • 00:47:55
    was able to improve the lactulose to
  • 00:47:57
    mannitol ratio and reduce people's on
  • 00:47:59
    Yulin levels when given 500 milligrams
  • 00:48:02
    up with 500 milligrams of bovine
  • 00:48:05
    colostrum per day so I know that I've
  • 00:48:10
    covered only a little bit of a lot of
  • 00:48:12
    things but I my job was to sort of give
  • 00:48:14
    this overview of barrier function and
  • 00:48:16
    what we can do about it so some of the
  • 00:48:18
    things you want to think about obviously
  • 00:48:19
    avoid foods that are going to create
  • 00:48:21
    intestinal permeability NSAIDs are a
  • 00:48:24
    real nono they're going to be a problem
  • 00:48:26
    so if you can all ask them to reduce or
  • 00:48:30
    eliminate their use of NSAIDs that's
  • 00:48:31
    going to help you dramatically reducing
  • 00:48:34
    stress we have time to talk about it but
  • 00:48:36
    stress obviously has a direct effect on
  • 00:48:38
    on the tight junctions avoiding
  • 00:48:42
    strenuous physical activity avoiding
  • 00:48:44
    processed foods with artificial colors
  • 00:48:46
    and flavors often these inflamed or
  • 00:48:48
    cause the same problems and eat abundant
  • 00:48:50
    amounts of fresh fruits and vegetables
  • 00:48:51
    maximize phytonutrient diversity and
  • 00:48:55
    then the list of things that I have here
  • 00:48:57
    are a little bit broader than what I'm
  • 00:48:58
    mention but you can see glutamine
  • 00:49:00
    vitamin D omega-3 fatty acids Pro and
  • 00:49:04
    prebiotics zinc can also be shown we see
  • 00:49:08
    we know that zinc deficiency can
  • 00:49:12
    increase intestinal permeability only
  • 00:49:14
    use iron if you've shown that they do
  • 00:49:16
    have iron deficiency don't just use that
  • 00:49:19
    prophylactically flavonoids colostrum
  • 00:49:22
    and then consider potentially berberine
  • 00:49:24
    especially of a you have a subject who
  • 00:49:26
    is insulin resistant and has type 2
  • 00:49:27
    diabetes where that would be beneficial
  • 00:49:29
    for other reasons so I went fairly
  • 00:49:34
    quickly and hopefully I've covered
  • 00:49:37
    enough that that we can get some
  • 00:49:40
    questions or at least follow-up later on
  • 00:49:42
    and that I'll hand it over to you now
  • 00:49:45
    Michael great thank you dr. Williams
  • 00:49:48
    just a terrific presentation we've
  • 00:49:50
    received a lot of feedback already and I
  • 00:49:53
    just want to remind everyone that the
  • 00:49:54
    PowerPoint will be available on our
  • 00:49:56
    website in PDF format next week we did
  • 00:49:59
    receive quite a few clinical questions
  • 00:50:00
    or general questions so let me just
  • 00:50:03
    start with there is a question around
  • 00:50:06
    research indicating that the potential
  • 00:50:08
    of overdosing or using a too much
  • 00:50:10
    supplementation with probiotics might
  • 00:50:13
    lead to increased immune load I didn't
  • 00:50:15
    know if you had any comment or if you
  • 00:50:17
    run across that so there are a lot of
  • 00:50:21
    clinicians that I think have been told
  • 00:50:23
    or just assumed that the use of
  • 00:50:25
    probiotics when you have some money that
  • 00:50:28
    let's say has high electives to mannitol
  • 00:50:30
    or suspicious of leaky gut that we
  • 00:50:33
    should avoid that because all of a
  • 00:50:34
    sudden we're going to create endotoxemia
  • 00:50:36
    or some other kind of thing I think
  • 00:50:38
    first of all there's no evidence of that
  • 00:50:39
    and two we would never imagine that
  • 00:50:42
    making the gut a septic is the solution
  • 00:50:45
    for a good barrier so as it turns out
  • 00:50:50
    from the data that we've seen and I
  • 00:50:52
    think just logically what we know about
  • 00:50:53
    good commensal organisms that the use of
  • 00:50:56
    probiotics is not contraindicated when
  • 00:50:59
    somebody has intestinal permeability or
  • 00:51:01
    leaky gut and in fact may actually be
  • 00:51:03
    beneficial so if you have if you believe
  • 00:51:07
    that your D getting endotoxemia because
  • 00:51:10
    you've got this major leaky gut you know
  • 00:51:12
    we're
  • 00:51:12
    not going to give antibiotics to wipe
  • 00:51:15
    out the gut so adding good bacteria is
  • 00:51:18
    certainly not going to be a problem it's
  • 00:51:19
    never been shown to be a problem and the
  • 00:51:21
    limited data we have suggested it's
  • 00:51:23
    actually beneficial great thank you
  • 00:51:26
    another question around whether you've
  • 00:51:28
    seen any research suggesting an impact
  • 00:51:31
    of Lyme STIs or other tick-borne
  • 00:51:33
    diseases on gut barrier function you
  • 00:51:39
    know I have never specifically looked at
  • 00:51:41
    that I would not at all be surprised if
  • 00:51:43
    there are some data suggesting that that
  • 00:51:45
    line lime or tick borne diseases are
  • 00:51:48
    really really any immune anything that
  • 00:51:51
    would affect the immune system that
  • 00:51:52
    dramatically would have gut barrier
  • 00:51:55
    changes but I have not specifically
  • 00:51:58
    looked at that or seen that report it
  • 00:52:00
    but it would not at all surprised me
  • 00:52:02
    another question about how long you know
  • 00:52:06
    kind of a timeline do you think that it
  • 00:52:08
    might take to to really restore repair
  • 00:52:10
    and inflamed GI tract and you know even
  • 00:52:13
    bring about better nutritional status
  • 00:52:16
    and and digestion absorption status so I
  • 00:52:20
    mean obviously that's very patient
  • 00:52:23
    specific if we if we step up back aways
  • 00:52:27
    and I don't want to make it seem like
  • 00:52:28
    the gut barrier is becomes everything we
  • 00:52:32
    if we back up and look at you obviously
  • 00:52:33
    the whole idea of what's going on in the
  • 00:52:36
    gut and you know the traditional sort of
  • 00:52:38
    for our approach and all these sort of
  • 00:52:40
    things it really depends if the first
  • 00:52:42
    are is to remove and you've got a
  • 00:52:45
    patient that is you know basically
  • 00:52:48
    sabotaging themselves with their own
  • 00:52:50
    diet routinely and they're exposed to
  • 00:52:54
    other things in their diet and alcohol
  • 00:52:56
    and other things and you're constantly
  • 00:52:57
    seeing a you know assault on on the gut
  • 00:53:00
    you know how long is it going to take
  • 00:53:02
    them to stop doing that so in one
  • 00:53:05
    subject you know you may be able to get
  • 00:53:08
    them to go cold turkey away from things
  • 00:53:10
    that are harming them others it may take
  • 00:53:11
    a long time so I think that's a that's a
  • 00:53:14
    huge part that I think people don't
  • 00:53:16
    realize you you know glutamine and you
  • 00:53:19
    know but phytochemicals and probiotics
  • 00:53:21
    in the midst of a diet that is
  • 00:53:24
    constantly assaulting the gut is is
  • 00:53:26
    take forever in fact it may never
  • 00:53:28
    benefit you so I think it really depends
  • 00:53:31
    I think if you have a very if you have a
  • 00:53:34
    compliant and a person that's willing to
  • 00:53:36
    change their diet very quickly I think
  • 00:53:39
    you can start seeing you know things
  • 00:53:40
    some people obviously within 3-4 days
  • 00:53:43
    you'll start seeing some dramatic
  • 00:53:44
    changes in some symptom ology if you've
  • 00:53:47
    got major breaches in the gut and you
  • 00:53:50
    know history of antibiotics and things
  • 00:53:52
    like that it may take a while to rebuild
  • 00:53:54
    but I would think you're going to see a
  • 00:53:56
    consistent increase month by month by
  • 00:53:58
    month and in some cases I think you
  • 00:54:01
    should if you're not seeing anything by
  • 00:54:02
    six months you probably are missing
  • 00:54:05
    something you might be missing a
  • 00:54:06
    parasite that you didn't recognize or
  • 00:54:08
    some other other thing going on and then
  • 00:54:10
    I think the issue is not the gut repair
  • 00:54:12
    process but really a diagnostic issue
  • 00:54:14
    what are you missing and so I think it's
  • 00:54:17
    going to be different for each
  • 00:54:18
    individual but it's not going to be
  • 00:54:20
    instantaneous
  • 00:54:21
    and these takes months in some cases
  • 00:54:23
    clinicians will tell you years to really
  • 00:54:25
    get to the point where the gut is not
  • 00:54:28
    vulnerable easily vulnerable to you know
  • 00:54:31
    just one you know off the wagon kind of
  • 00:54:33
    thing great um I found an interesting
  • 00:54:37
    you mentioned that the large intestine
  • 00:54:39
    really kind of acts as a fermenting
  • 00:54:40
    vessel and so what are some of the
  • 00:54:43
    changes that you might see or expect to
  • 00:54:46
    see in the development of small
  • 00:54:47
    intestinal bacterial overgrowth
  • 00:54:49
    and and kind of your thoughts around how
  • 00:54:52
    the etiology how that might develop and
  • 00:54:56
    so if you if you and this is a kind of a
  • 00:55:00
    tricky subject but if you look at small
  • 00:55:02
    intestinal bacterial overgrowth and what
  • 00:55:05
    we do to define it now again the gold
  • 00:55:07
    standard for that is actually you know
  • 00:55:09
    aspiration of the duodenum or the ileum
  • 00:55:11
    and actually counting bacteria and
  • 00:55:13
    getting a numbering saying that we
  • 00:55:15
    actually have an overgrowth in the small
  • 00:55:17
    intestine the other issue the other way
  • 00:55:19
    to look at that is a breath test and a
  • 00:55:22
    breath test is and if we don't time to
  • 00:55:23
    get into that a breath test positive can
  • 00:55:27
    be SIBO can be overgrowth of bacteria
  • 00:55:29
    but it can be anything that creates that
  • 00:55:32
    fermentation early which can be bowel
  • 00:55:34
    trying to time which can be even certain
  • 00:55:36
    bacteria in the small bowel whether
  • 00:55:38
    they're overgrown overall or not
  • 00:55:40
    so it gives us some idea that something
  • 00:55:42
    is going on and we have symptom ology
  • 00:55:44
    based on you know sort of this
  • 00:55:46
    fermentation process so the the small
  • 00:55:50
    intestine should not be a fermenting of
  • 00:55:53
    vessel typically and typically the
  • 00:55:57
    lactobacilli and the bit you know like a
  • 00:55:59
    basilica that are reside there and other
  • 00:56:00
    bacteria that reside there are there
  • 00:56:02
    typically doing other things and one of
  • 00:56:05
    the things that they're doing is they're
  • 00:56:07
    having much more interaction with the
  • 00:56:08
    immune system and so that's why even
  • 00:56:10
    small amounts of bacteria lack of a
  • 00:56:12
    silly we say well you know it seems like
  • 00:56:13
    a drop in the bucket compared to what's
  • 00:56:15
    in the colon but if they're in the small
  • 00:56:18
    intestine they don't need high doses we
  • 00:56:20
    don't need high amounts that are there
  • 00:56:22
    because they're doing other sorts of
  • 00:56:23
    things so we certainly about transit
  • 00:56:27
    time is slow if acid is low if other
  • 00:56:29
    things are going on you can get this
  • 00:56:31
    migration of bacteria from the colon
  • 00:56:34
    into the small intestine which creates
  • 00:56:35
    problems some of which we can measure
  • 00:56:38
    when we do either the glucose or lactose
  • 00:56:41
    test for the breath but may or may not
  • 00:56:45
    be SIBO in many of those cases great
  • 00:56:48
    yeah and I know that was a very large
  • 00:56:50
    topic probably its own webinar we had a
  • 00:56:52
    lot of questions around where a lot of
  • 00:56:55
    questions about the book so I just want
  • 00:56:56
    to give you an opportunity to inform the
  • 00:56:58
    audience about where they can get the
  • 00:57:00
    book and n speak to that so you know the
  • 00:57:04
    book is published to the point Institute
  • 00:57:06
    and you can you can purchase the book
  • 00:57:08
    through what's called a lifestyle matrix
  • 00:57:10
    resource center l MRC we call it a
  • 00:57:13
    lifestyle matrix resource center and so
  • 00:57:15
    it's if you look it up online lifestyle
  • 00:57:18
    matrix you can you can find it there and
  • 00:57:22
    you can purchase it directly
  • 00:57:25
    I don't know of Genova actually is if
  • 00:57:28
    you can create a link for that and let
  • 00:57:30
    people have a link directly to that the
  • 00:57:32
    book is over 250 pages or actually 250
  • 00:57:37
    pages basically divided into those five
  • 00:57:40
    different areas so fundamentally
  • 00:57:42
    teaching each of those principles like
  • 00:57:44
    that you can see some of the figures I
  • 00:57:46
    showed it basically the teaching manual
  • 00:57:48
    for GI function and then there's a
  • 00:57:51
    series of monographs at the end they
  • 00:57:53
    go through things like feeble IBS IBD h
  • 00:57:57
    pylori etc and going through sort of
  • 00:58:01
    summarizing the the evidence for the
  • 00:58:04
    traditional and the functional approach
  • 00:58:07
    to treating those so the goal of the
  • 00:58:10
    book is really to bring together the
  • 00:58:12
    evidence for the common functional
  • 00:58:14
    medicine approach to these in some cases
  • 00:58:18
    you know we show the evidence in some
  • 00:58:20
    cases we suggest like we did today that
  • 00:58:21
    there's good you know fundamental
  • 00:58:25
    mechanisms but we don't have what we'd
  • 00:58:27
    like to have as far as you know a deep
  • 00:58:29
    clinical trial evidence for some of the
  • 00:58:32
    things that we often use great and and
  • 00:58:35
    just thank you so much again in the
  • 00:58:37
    interest of time we're gonna end our
  • 00:58:38
    question and answer period there for any
  • 00:58:41
    additional educational materials we'd
  • 00:58:43
    like to encourage you to visit our
  • 00:58:44
    website www.investmentpitch.com
  • 00:59:26
    it was my pleasure to be with you
标签
  • gut health
  • barrier function
  • Dr. Thomas Williams
  • dietary supplements
  • leaky gut
  • microbial ecosystem
  • intestinal permeability
  • functional medicine
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