Course Breakdown: GUT MICROBIOTA - Wisconsin Chiropractic Association

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Course Breakdown: GUT MICROBIOTA - Wisconsin Chiropractic Association
3/29/2021

             GUT MICROBIOTA
                    ©Jeff Lavell, DC

                Normal anatomy of lower GI

                Aspects of the microbiome

                Fiber/pre‐biotics

Course          Pro‐biotics

Breakdown:      Abnormal Gut Pathology
                •   Gut dysbiosis
                •   IBS/IBD
                •   Leaky gut
                •   SIBO

                Gut Protocols

                    ©Jeff Lavell, DC

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Course Breakdown: GUT MICROBIOTA - Wisconsin Chiropractic Association
3/29/2021

 Prevalence of Digestive Issues
• Rarely mentioned as a health problem, more of an
  inconvenience!
• 38 million Americans are victims of digestive disorders,
  including Crohn’s disease, ulcerative colitis,
  diverticulitis, celiac disease, IBS, constipation,
  diarrhea, GERD, candida and food allergies.
• Economic impact of digestive disorders is $142 billion
  per year (1), compared to $124.5 billion for cancer, $58
  billion for neurological disorders, and $88 billion for
  circulatory problems.
• “Sufferers from IBS (the most common gastrointestinal
  disorder) incur an estimated $10 billion more in direct
  medical charges per year than a similar control group
  of people the same age and gender.”
    • From Weston A Price Foundation
    • (1) Peery AF, Dellon ES, Lund J, et al. Burden of Gastrointestinal
        Disease in the United States: 2012 Update. Gastroenterology.
        2012;143(5):1179‐1187.                                       ©Jeff Lavell, DC

 Common Complaints
• Poor taste                   • Slow bowels
• Gas                          • Loose bowels
• Bloating                     • Sticky bowels
• Nausea                       • Irregular bowels
• Burning/heartburn

What The Patient Thinks
   Is Right/Normal
• Tums                          • Loose stools
• OTC Prilosec                  • Constipation
• Pepto Bismol/Malox • “It’s just the way I
• Rx: Omeprazole       am”
                                                                       ©Jeff Lavell, DC

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Course Breakdown: GUT MICROBIOTA - Wisconsin Chiropractic Association
3/29/2021

What we should think

• That most patients have conditions that
  can be helped and basic physiologic
  principals apply regardless of patient or
  condition.
• We will approach this as a “system” and
  utilize basic physiologic and nutritional
  principals to address key areas to create
  the clinical outcome we desire!

                                      ©Jeff Lavell, DC

Large Intestine
Anatomy
• Colon (large intestine)
    • Ileocecal valve
    • Ascending colon
    • Transverse colon
    • Descending colon
    • Sigmoid colon
    • Rectum

                                      ©Jeff Lavell, DC

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Course Breakdown: GUT MICROBIOTA - Wisconsin Chiropractic Association
3/29/2021

Large Intestine

• the mucosa of the large intestine does
  contain a large number of goblet cells.
  Goblet cells are specialized epithelial cells
  that secrete mucus.
• The mucus produced by the goblet cells act
  as a lubricant to ease the passage of feces

                                                  ©Jeff Lavell, DC

                                                          Absorb water (although the majority is
                                          Absorb absorbed in small intestine)

Colon                                       Feed
                                                          Feed bacteria
                                                          • Produces Vitamins
Functions
                                                          Promote defecation
                                         Promote          • Should take 18‐24 hours from mouth to excretion.

                                                  ©Jeff Lavell, DC

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Course Breakdown: GUT MICROBIOTA - Wisconsin Chiropractic Association
3/29/2021

                                                        Role of Water in
                                                        Bowel Function

                                                 ©Jeff Lavell, DC

       Action of colon with water

• Water reabsorption is a main function of the large intestine. It can absorb 300 ml, or about a cup and a
  half, of water a day.
• This water removal dries out the feces. If food moves through the large intestine too quickly, it will not
  have sufficient time to absorb water, which will result in the passage of watery stool, or diarrhea. By
  contrast, when food residue remains in the large intestine for an extended period of time, too much
  water can be absorbed. This can result in constipation, which is defined as a hard stool or difficulty
  passing stool. Constipation may be due to a lack of fiber in the diet.
• Any remaining nutrients from food are absorbed here before sending the indigestible matter to the
  rectum.
• The colon absorbs vitamins that are created by the colonic bacteria, such as vitamin K (especially
  important as the daily ingestion of vitamin K is not normally enough to maintain adequate blood
  coagulation), vitamin B12, thiamine and riboflavin.
    • Source: Guyton and Hall Textbook of Medical Physiology
                                                 ©Jeff Lavell, DC

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Course Breakdown: GUT MICROBIOTA - Wisconsin Chiropractic Association
3/29/2021

Everybody
Poops
            ©Jeff Lavell, DC

                               Bristol Stool
                               Chart

            ©Jeff Lavell, DC

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Course Breakdown: GUT MICROBIOTA - Wisconsin Chiropractic Association
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               “All Disease
Hippocrates
              Begins In The
                  Gut.”
                ©Jeff Lavell, DC

              Gut Health & Microbiota
               • Gut health is multifaceted.
               • Nutrition, environmental toxins, and ability to
                 eliminate waste all have huge factors in gut
                 health.
               • Recent research has shown gut health even
                 has a key impact on brain health! (more on
                 that later)

                ©Jeff Lavell, DC

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Course Breakdown: GUT MICROBIOTA - Wisconsin Chiropractic Association
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    What We Know About The Gut Flora So Far…

        1                              2                               3                                4                               5                          6
10x the number               Contains 150x                   Is 2 to 5 pounds                 Half your stool is              Your gut is as               Diversity is the
of bacteria in the           more genes as in                of your weight.                  microbial mass.                 individual as your           key, as close to
gut as there are             our genome.                                                                                      fingerprint.                 1000 different
cells in the body!                                                                                                                                         bacterial types
                                                                                                                                                           are possible.

                             Source: Dinan, Tmothy G, Caterhine Stan "Psychobiotics: A Novel Class of Psychotropic" by Timothy G. Dinan, Catherine
                             Stanton, and John F. Cryan. Biological Psychiatry, Volume 74, Issue 10 (November 15, 2013), published by Elsevier
                             Source: Noah Fierer. Forensic identification using skin bacterial communities. PNAS April 6, 2010 vol. 107 no. 14 6477‐6481

                                                                                  ©Jeff Lavell, DC

           Microbes are part of the whole body health
                    influence of the GI tract                                                                              Gastrointestinal
                                                                                                                           Microbiota

http://journal.frontiersin.org/article/10.3389/fnint.2013.00070/full
http://www.nature.com/nrmicro/journal/v11/n4/fig_tab/nrmicro2974_F1.html
                                                            ©Jeff Lavell, DC

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Course Breakdown: GUT MICROBIOTA - Wisconsin Chiropractic Association
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                                          • Gut flora helps you to maintain weight or even
                                            lose weight!
                                              • Palmas V, Pisanu S, Madau V, et al. Gut microbiota
                                                markers associated with obesity and overweight in
                                                Italian adults. Sci Rep. 2021;11(1):5532.
                                              • Stanislawski MA, Dabelea D, Wagner BD, et al. Gut
 Gut Health For                                 Microbiota in the First 2 Years of Life and the
                                                Association with Body Mass Index at Age 12 in a
  Weight Loss?                                  Norwegian Birth Cohort. mBio. 2018;9(5):e01751‐
                                                18.
                                              • Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel
                                                BL, Duncan A, Ley RE, Sogin ML, Jones WJ, Roe BA,
                                                Affourtit JP, Egholm M, Henrissat B, Heath AC,
                                                Knight R, Gordon JI. A core gut microbiome in obese
                                                and lean twins. Nature. 2009 Jan 22;457(7228):480‐
                                                4. doi: 10.1038/nature07540. Epub 2008 Nov 30.

                                             ©Jeff Lavell, DC

E. Coli is a major bacteria in the gut
• Somewhere between 300 and
1000 different species live in the gut,
with most estimates at about 500.
However, it is probable that 99% of
the bacteria come from about 30 or
40 species.

•        Source: Beaugerie L, Petit
JC (April 200Microbial-gut
interactions in health and disease.
Antibiotic-associated diarrhoea".
Best Pract Res Clin Gastroenterol
18 (2): 337–52

                                            ©Jeff Lavell, DC

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Course Breakdown: GUT MICROBIOTA - Wisconsin Chiropractic Association
3/29/2021

                                                                                        Potential
                                                                                        Harmful and
                                                                                        Beneficial
                                                                                        Functions
                                                                                        • Generalized scheme of
                                                                                        predominant groups of
                                                                                        colonic bacteria, indicating
                                                                                        how the genera may exhibit
                                                                                        potentially harmful and
                                                                                        beneficial functions.
                                                                                        Guarner F. Digestion 2006;
                                                                                        73(Suppl 1): 5-12

                                                    ©Jeff Lavell, DC

                          What Does The Gut
                           Microbiota Do?
            1                          2                                  3                                4
Digestion                  Synthesize nutrients                   Immune system                   Neurotransmitters (1)

                (1) Source: O’Mahony, S.M. et al. “Serotonin, tryptophan metabolism and the brain gut
                            microbiome axis.” Behavioural Brain Research 277 (2015): 32‐48
                                                    ©Jeff Lavell, DC

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  Gut Microbiota And Nutrition

  • Several bacterial genera that are common in the distal intestine
    (e.g., Bacteroides, Bifidobacterium, and Enterococcus) are known to
    synthesize vitamins. Thiamine, folate, biotin, riboflavin, and panthothenic
    acid are water‐soluble vitamins that are plentiful in the diet, but that are
    also synthesized by gut bacteria. Likewise, it has been estimated that up to
    half of the daily Vitamin K requirement is provided by gut bacteria [1].

     (1) Source: Eur J Cancer Prev. 1997 Mar;6 Suppl 1:S43‐5.
     Intestinal flora and endogenous vitamin synthesis. Hill MJ.

                                    ©Jeff Lavell, DC

Gut Flora & The Neurotransmitters They Contribute

                                                             Gamma‐
       Dopamine                   Serotonin                aminobutyric
                                                            Acid (GABA)

                                    ©Jeff Lavell, DC

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An Example: serotonin
• “Peripheral serotonin is produced in the digestive tract by
  enterochromaffin (EC) cells and also by particular types of immune
  cells and neurons. Hsiao and her colleagues first wanted to know if
  gut microbes have any effect on serotonin production in the gut
  and, if so, in which types of cells. They began by measuring
  peripheral serotonin levels in mice with normal populations of gut
  bacteria and also in germ‐free mice that lack these resident
  microbes.”
• “The researchers found that the EC cells from germ‐free mice
  produced approximately 60 percent less serotonin than did their
  peers with conventional bacterial colonies. When these germ‐free
  mice were recolonized with normal gut microbes, the serotonin
  levels went back up—showing that the deficit in serotonin can be
  reversed.”
    • ‐ See more at: http://www.caltech.edu/news/microbes‐help‐produce‐
      serotonin‐gut‐46495#sthash.Q76q5fdw.dpuf

                                               ©Jeff Lavell, DC

                                         • Recent research supporting a role for the
            Gut                            microbiota in maintaining normal brain
         Health                            function offers the intriguing possibility that
                                           the therapeutic targeting of the gut
        And The                            microbiome might be a viable strategy in in
                                           supporting CNS health (Forsythe et al., 2010).
          Brain

                                         Source: Grenham S, Clarke G, Cryan JF, Dinan TG. Brain–
                                         Gut–Microbe Communication in Health and Disease.
                                         Frontiers in Physiology. 2011;2:94.
                                         doi:10.3389/fphys.2011.00094.

                                               ©Jeff Lavell, DC

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  Bacteria In Your Gut And Mood
  • Originally studied in mice in 1990 (in Mankato!) researchers first noticed that
    stressed mice were more likely to get sick, and theorized that the bugs caused
    the infections.
  • So they decided to test if the microorganisms that relate to disease are affected
    by stress. When they added norepinephrine to a petri dish of bacteria there was
    a huge increase in growth of the bacteria, the non norepinephrine dishes did not
    show that at all.
  • Then, to see if bacteria could induce stress, mice were fed a liquid solution of
    Campylobacter jejuni, a bacterium that can cause food poisoning in humans but
    generally doesn’t prompt an immune response in mice.
  • When he ran them through a plexiglass maze raised several feet above the lab
    floor, the bacteria‐fed mice were less likely to venture out on the high,
    unprotected ledges of the maze. In human terms, they seemed anxious. Without
    the bacteria, they walked the narrow, elevated planks.
  • Therefore, introducing a pathological bacterium into the gut will cause a change
    in behavior.’
  • This has begun to show in human studies as well.

                                                       ©Jeff Lavell, DC

Gut Health &
Inflammation
• Studies have shown elevations of
  TNF-α, IL-1β, IL-6 with poor gut
  health.
   • Source: Grenham S, Clarke G, Cryan
     JF, Dinan TG. Brain–Gut–Microbe
     Communication in Health and
     Disease. Frontiers in Physiology.
     2011;2:94.
     doi:10.3389/fphys.2011.00094

                                                       ©Jeff Lavell, DC

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                                        Vagus nerve innervates the digestive tract.

                                        Poor vagal activity = decreased pancreatic enzyme secretion, poor
                                        gallbladder function, and poor gut function overall. It also suppresses the
                                        intestinal immune system and decreases intestinal blood flow.

Nerve Impact                            This leads to increased growth in pathogenic yeast and bacteria, that cause
                                        intestinal permeability or leaky gut, leaky gut causes a state of chronic low
                                        grade inflammation.
With Gut                                Inflammatory cytokines produced in the gut travel through the blood and
Health                                  they cross the blood‐brain barrier.

                                        Inflammatory cytokines once they get into the brain activate the microglial
                                        cells.

                                        Microglial cells are the immune cells of the brain and once they’re activated
                                        by these inflammatory cytokines this is basically inflammation of the brain.

                                           ©Jeff Lavell, DC

Nerve Impact With Gut Health

                                                                        80% of total            So the gut
                                           Enteric nervous            serotonin in the          communicates
                                                 system              body is located in         with the brain via
   The enteric       It is considered         generates                       the               cytokines and gut
 nervous system       to be separate      intestinal motility        enterochromaffin           opiates and gut
    has been              from the           and enzyme                cells in the gut         peptides like
referred to as the       autonomic       release and then             and this is used          neurotensin and
  second brain.      nervous system.          it provides               primarily to            substance-P.
                                         incoming input to                regulate              •Source: Wikipedia
                                         the vagus nerve.              peristalsis and
                                                                           motility.

                                           ©Jeff Lavell, DC

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                                                Fiber
                     Supporting A Healthy Gut

 “In populations in which fiber constitutes a major
   portion of the diet conditions such as diarrhea,
hemorrhoids, gallstones, hiatal hernia, varicose veins,
    appendicitis and heart disease are unknown”

                 Denis Parsons Burkitt
           (28 February 1911 – 23 March 1993)

                        ©Jeff Lavell, DC

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Fiber
•Benefits
   • Decreases GI transit time
   • Increases water retention without osmotic
     imbalance
   • Provides a substrate for symbiotic colonic
     bacteria
   • Reduces glycemic load of foods ingested
   • Improves transit time in the gut
   • Reduces haustra formation in diverticulitis
   • Improves tone of GI smooth muscle
        • Note: the vast majority of diverticulitis
          cases are caused by insufficient dietary
          fiber

    • Any downside???
                                             ©Jeff Lavell, DC

         Gas!

                                              ©Jeff Lavell, DC

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                Fiber

    •Two basic types:
       • Soluble
       • Insoluble

                                                  ©Jeff Lavell, DC

    Soluble Fiber
• These include mucilages, pectins, and gums.
• These substances form a gel which mixed with
  liquid and increase bulk.

  Found abundantly in:

 • Avacados (10.5 grams    • Peas(split peas 16
   per cup)                  grams per cup)
 • Artichokes (10 grams    • Lentils (15 grams per
   per cup)                  cup)
 • Prunes                  • Barley
 • Flaxseed                • Carrots
 • Oats                    • Potatoes (particularly
 • Legumes (varies by        the skins)
   type, but most around   • Apples
   13-15 grams per cup)    • Psyllium
                           • Berries

                                                  ©Jeff Lavell, DC

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                                                    Insoluble Fiber
                                      •This fiber does not gel.
                                      •Found in:
                                          • Wheat
                                          • Brown rice and other unrefined grains
                                          • Unprocessed vegetables
                                          • Fruits
                                          • Green leafy veggies
                                          • Edible seeds (sunflower, pumpkin, &
                                            sesame)

                                      ©Jeff Lavell, DC

Mop vs. Broom
•Soluble and insoluble fibers ought
to be eaten mostly raw.
    • Eating Raw is like a broom.
    • Cooking breaks down fiber
      and instead of getting a
      broom you end up with a
      mop.

                                      ©Jeff Lavell, DC

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How Much Fiber?
•12-17 grams is adequate
•20-35 grams is ideal

                                      ©Jeff Lavell, DC

How Much Water
When Increasing Fiber?
•A few people will report bloating or an
increase in constipation when taking fiber.
    • This is due to two factors:
       • Too much fiber, too soon
       • Too little water with the increase
          in fiber
            • Different fibers will absorb
               anywhere from 3 to 5 times
               their weight in water

                                       ©Jeff Lavell, DC

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             Non digestible starches that selectively stimulate
             the growth of symbiotic bacteria in the colon.
                 • FOS: fructooligosaccharides
                 • Arabinogalactans - from larch tree
                 • Galacto-oligosaccharides
Prebiotics       • Inulin

                       • Lactobacilli and bifidobacteria use
                         these as a substrate to grow upon

               ©Jeff Lavell, DC

                                             Brain Maker
                                  “It’s important to get back to foods that are rich in
                                  prebiotic fiber—which is a unique type of fiber.
                                  Foods like jicama, Mexican yam, asparagus,
                                  dandelion greens, garlic and onions are foods
                                  that contain high levels of a particular type of
                                  prebiotic fiber that’s called inulin. Inulin is really
                                  helpful in terms of nurturing good gut bacteria.
                                  Our healthy gut populations use prebiotic fiber
                                  such as inulin to multiply and to increase their
                                  metabolism, and facilitate the creation of amino
                                  acids, the provision of vitamins, the reduction of
                                  gut permeability, and therefore inflammation.
                                  They even facilitate the creation of serotonin and
                                  dopamine!”

                                                   Source: Brain Maker: The Power of
                                                   Gut Microbes to Heal and Protect
                                                   Your Brain–for Life. David Perlmutter
                                                   Little, Brown, Apr 28, 2015

               ©Jeff Lavell, DC

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      Prebiotic: 2’‐
 FUCOSYLLACTOSE (2’FL)
    Supports a Healthy
       Microbiome

Chemically equivalent to the most
abundant Human Milk
Oligosaccharide. Not normally
consumed by adults.
   • Selectively supports the growth
     of beneficial bacteria
   • Supports a healthy microbiome
      • Elison, E., et al., Oral supplementation
        of healthy adults with 2'-O-
        fucosyllactose and lacto-N-neotetraose
                                                                Baseline                              2’FL intervention
        is well tolerated and shifts the                    Microbial Phylum                          Microbial Phylum
        intestinal microbiota. Br J Nutr, 2016.                 Diversity                                 Diversity
        116(8): p. 1356-1368.
                                                   ©Jeff Lavell, DC

                                                                          • Deficiencies in butyrate producing
                                                                            bacteria and decreased colonic
                                                                            expression of the butyrate transporter
                                                                            monocarboylate transporter-1 have
                                                                            been observed in IBD patients.1,2
                                                                          • Clinical trials have indicated resistant
                                                                            starch supplementation significantly
                                                                            increased butyrate concentrations.3,4,5
                                                                          • Butyrate regulates neutrophil function,
                                                                            increase tight junction protein
                                                                            expression, and reduces cytokine and
                                                                            chemokine release.6
                                                                          • Butyrate has also been shown to
                                                                            promote fluid and electrolyte
                                                                            absorption in the gut.6
                                                                          • Green Bananas are a low FODMAP
                                                                            food, therefore green banana
                                                                            resistant starch would be a low
                                                                            FODMAP ingredient.
                                                                               1ThibaultR et al. 2010. Inflamm Bowel Dis.

                        Resistant Starch
                                                                               2Machiels  K et al. 2014. Gut.
                                                                               3AlfaMJ et al. 2018. Clinical Nutr.
                                                                               4Venkataraman A et al. 2016. Microbiome.
                                                                               5Baxter NT et al. 2019. MBio.
                                                                               6Shin A et al. 2018. Clin Gastroentero Hep

                                                   ©Jeff Lavell, DC

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      Fermentate:
      Also known as: Whole food fermentate, dried
      fermentate, yeast fermentate or dried yeast fermentate

      • Nutritious whole food product made using a
        unique, specialized fermentation process.
      • Made using specific yeast strain Saccharomyces
        cerevisiae (bakers yeast)
         • Fed proprietary nutrients
         • Specialized anaerobic fermentation process
      • Immune-related benefits
      • Prebiotic-like properties
         • May modulate the composition of the gut
           microbiome1
               •   1Pinheiro I et al. 2017. BMC Complement Altern
                   Med.

                                                        ©Jeff Lavell, DC

     Fiber and prebiotics

It’s been estimated the average American
consumes about 5g a day of prebiotic fiber in
comparison to our Paleolithic ancestors, who
may have consumed as much as 135g in a
single day.
    Source: Brain Maker: The Power of Gut Microbes to
    Heal and Protect Your Brain–For Life David
    Perlmutter , MD, FACN, ABIHM is a Board-Certified
    Neurologist and Fellow of the American College of
    Nutrition

                                                        ©Jeff Lavell, DC

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Probiotics
  ©Jeff Lavell, DC

                        Probiotics
                         function
                        through a
                        variety of
                       mechanisms

                      O’Toole, P.W. and Cooney,
                     J.C. Interdisciplinary
                     Perspectives on Infectious
  ©Jeff Lavell, DC   Diseases, 2008:175285.

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                 • Note: all the lactobacilli require sugar to grow

Probiotics       • Unprocessed fermented foods are rich in these bacteria
                 • Bacteriocin production is also generally regarded as
                   a probiotic trait

               ©Jeff Lavell, DC

             Lactobaccillus acidophilus

             Bifidobacterium bididum

Probiotics   L. bulgaricus
             • Note: all the lactobacilli
               require milk sugar (lactose) to
               grow
             • Unprocessed fermented foods
               are rich in these bacteria
               ©Jeff Lavell, DC

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                  Lactobacillus acidophilus (including LA‐5®)—The LA‐5 strain has been
                  evaluated for its ability to interfere with the communication between
                  other types of bacteria, thus promoting a healthy balance of microbes.
                  The LA‐5 strain was also among several other lactobacilli that improved
Clinically        outcomes in subjects with occasional constipation, as well as those with
                  lactose tolerance challenges.*
Documented
Strains That      Lactobacillus paracaseissp. paracasei (L.casei 431®)—To support the
                  natural gut environment, this strain of lactic acidproducing bacteria
Work              adheres to the intestinal tract and tolerates bile. This strain has been
                  studied in humans and mice for its ability to support the gut during
                  challenges and for its ability to help maintain the body's natural immune
Synergistically   system response.*

With Prebiotic    Bifidobacterium lactis (BB‐12®)—Bifidobacteria are very tolerant of both
Fibers.           acidic conditions and environments that contain bile. Bifidobacteria use a
                  range of carbohydrates for energy (including GOS). Bifidobacteria are an
                  important factor in all native microflora and their numbers vary depending
                  on lifestyle, diet, exercise and age. Oral bifidobacteria have been shown to
                  temporarily colonize the gut, competing with other bacteria to effectively
                  support the natural bacterial balance.*

                     ©Jeff Lavell, DC

                  Saccharomyces cerevisiae (brewers yeast) var. boulardii—
                  Historically, this microbe was used to support normal stool
Clinically        consistency. In the gut, this yeast supports the growth of
                  some bacteria and inhibits others through competition and
Documented        environmental modification of the gut.*

Strains That      Inulin—Inulin is a complex carbohydrate that can be
Work              digested by certain microorganisms, providing them with
                  energy. Inulin supports the absorption of calcium and
Synergistically   magnesium.*
With Prebiotic
Fibers.           Galactooligosaccharide (GOS)—Research suggests that
                  GOS is a preferred substrate for BB‐12. In mice, GOS
                  supplementation supported the active proteins and cells in
                  the gut mucosa, and increased the amount of short‐chain
                  fatty acid and lactate in the gut.*

                     ©Jeff Lavell, DC

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  “Research shows that friendly bacteria survive transit
 through the acid environs of the stomach to the lower GI
     when ingested with naturally fermented foods”
    Source: P. Marteau. Survival of Lactic Acid Bacteria in a Dynamic Model of the Stomach and Small
      Intestine: Validation and the Effects of Bile. Volume 80, Issue 6, Pages 1031‐1037 (June 1997)

                                               ©Jeff Lavell, DC

                                                                  Eat Bacteria Rich Food
                                                                  •   Kimchee
                                                                  •   Kombucha
                                                                  •   Cultured yogurt
                                                                  •   Raw milk/Kefir
                                                                  •   Sauerkraut
                                                                  •   Fermented meats
                                                                  •   Fermented vegetable

                                                                            •      Source: Brain Maker: The Power of
                                                                                   Gut Microbes to Heal and Protect
By Gandydancer (original file) via Wikimedia                                       Your Brain–for Life. David Perlmutter
                                                                                   Little, Brown, Apr 28, 2015

                                               ©Jeff Lavell, DC

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Acidify GI tract
(alkalizing)
• A number of ways to do it.
    • Apple Cider Vinegar (a number of recipes
      are available)
        • Recipe I like is tablespoon Bragg's
           Raw Apple Cider Vinegar 1
           tablespoon raw local honey or maple
           syrup 6 ounces of filtered
           water…drink 3x per day.
    • Supplement with products that acidify the
      GI tract.
        • Best one is of course Lactic Acid
           producing products help.

                                             ©Jeff Lavell, DC

                             Gut Dysbiosis

                                             ©Jeff Lavell, DC

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Aberrant
Intestinal
Microbiota
• The intestinal microbiome
  is established at birth
     • Diets high in refined
       carbohydrate and low
       in fiber will alter the
       biome and favor
       unfriendly bacteria.
     • A history of antibiotic
       use will alter bacterial
       gut composition

                                     ©Jeff Lavell, DC

                                  Antibiotics & Gut Dysbiosis
                                  • “The primary cause of dysbiosis is the use of
                                    antibiotics, which kill >99% of the good
                                    bacteria. Other factors that can cause or
                                    contribute to the development of dysbiosis
                                    include stress, birth control pills, and junk
                                    foods.”
                                           • Source: Ross Pelton, RPh, PhD, CCN.
                                             Antibiotics, Probiotics, and Microflora.
                                             Published Online: July 1, 2005.
                                             http://www.pharmacytimes.com/issue/phar
                                             macy/2005/2005-07/2005-07-9743

                                     ©Jeff Lavell, DC

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      4 years of disturbance?
    Abstract
    • Antibiotic administration is the standard treatment for the bacterium Helicobacter pylori, the main causative
      agent of peptic ulcer disease and gastric cancer. However, the long-term consequences of this treatment
      on the human indigenous microbiota are relatively unexplored. Here we studied short- and long-term
      effects of clarithromycin and metronidazole treatment, a commonly used therapy regimen against H.
      pylori, on the indigenous microbiota in the throat and in the lower intestine. The bacterial compositions in
      samples collected over a four-year period were monitored by analyzing the 16S rRNA gene using 454-
      based pyrosequencing and terminal-restriction fragment length polymorphism (T-RFLP). While the
      microbial communities of untreated control subjects were relatively stable over time, dramatic shifts were
      observed one week after antibiotic treatment with reduced bacterial diversity in all treated subjects in both
      locations. While the microbiota of the different subjects responded uniquely to the antibiotic treatment
      some general trends could be observed; such as a dramatic decline in Actinobacteria in both throat and
      feces immediately after treatment. Although the diversity of the microbiota subsequently recovered to
      resemble the pre treatment states, the microbiota remained perturbed in some cases for up to four
      years post treatment. In addition, four years after treatment high levels of the macrolide resistance gene
      erm(B) were found, indicating that antibiotic resistance, once selected for, can persist for longer periods of
      time than previously recognized. This highlights the importance of a restrictive antibiotic usage in order to
      prevent subsequent treatment failure and potential spread of antibiotic resistance.
           • Source: Jakobsson HE, Jernberg C, Andersson AF, Sjölund-Karlsson M, Jansson JK, Engstrand L. Short-Term Antibiotic Treatment
             Has Differing Long-Term Impacts on the Human Throat and Gut Microbiome. Ratner AJ, ed. PLoS ONE. 2010;5(3)
                                                               ©Jeff Lavell, DC

                    Antibiotics, Children & Food Allergies
Abstract
• Background: To assess the relationship between any systemic antibiotic prescription within the first year of life and the
  presence of an ICD‐9‐CM diagnosis code for food allergy (FA). Methods: This was a matched case–control study conducted
  using South Carolina Medicaid administrative data. FA cases born between 2007 and 2009 were matched to controls
  without FA on birth month/year, sex, race/ethnicity. Conditional logistic regression was used to model the adjusted odds
  ratio (aOR) of FA diagnosis. All models were adjusted for presence of asthma, wheeze, or atopic dermatitis. Results: A
  total of 1504 cases and 5995 controls were identified. Receipt of an antibiotic prescription within the initial 12 months of
  life was associated with FA diagnosis in unadjusted and adjusted models (aOR 1.21; 95 % CI 1.06–1.39). Compared to
  children with no antibiotic prescriptions, a linear increase in the aOR was seen with increasing antibiotic prescriptions.
  Children receiving five or more (aOR 1.64; 95 % CI 1.31–2.05) antibiotic prescriptions were significantly associated with FA
  diagnosis. The strongest association was noted among recipients of cephalosporin and sulfonamide antibiotics in both
  unadjusted and adjusted models.
• Conclusions: Receipt of antibiotic prescription in the first year of life is associated with FA diagnosis code in young
  children after controlling for common covariates. Multiple antibiotic prescriptions are more strongly associated with
  increases in the odds of FA diagnosis
    • Source: Love BL, Mann JR, Hardin JW, Lu ZK, Cox C, Amrol DJ. Antibiotic prescription and food allergy in young children. Allergy,
      Asthma, and Clinical Immunology : Official Journal of the Canadian Society of Allergy and Clinical Immunology. 2016;12:41.
                                                                ©Jeff Lavell, DC

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Gut Dysbiosis

• Imbalance of the good to
  bad bacteria in the gut.
• Heavily involved in other gut
  conditions, like leaky gut,
  IBS, and IBD!

                                  ©Jeff Lavell, DC

                  Gut Disbiosis Symptoms

                                  ©Jeff Lavell, DC

                                                           30
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How to
Determine is
Dysbiosis
Exists?

                    ©Jeff Lavell, DC

          Gut Dysbiosis: IBD & IBS

                    ©Jeff Lavell, DC

                                             31
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                                        • A syndrome has no definitive
                                          diagnostic criteria.
                     Irritable bowel    • More of a collection of symptoms
                     syndrome (IBS)       that matches…disease of
                                          elimination rather than
                                          confirmation.

 Lower GI
 pathophysiology
                                        • Highly related to the gut flora
                     Inflammatory         balance in the gut (gut dysbiosis)
                         Bowel          • Chief diagnostic criteria are:
                   Disease/Ulcerative
                      Colitis (IBD)       • Bleeding mucosa
                                          • Frank blood in stools

                    ©Jeff Lavell, DC

                                             •Symptoms may occur alone
Signs & Symptoms                             or in combination with other
                                             symptoms such as:
                                                      • Bloating
                                                      • Abdominal
                                                        discomfort
                                                      • Increased
                                                        frequency of bowel
                                                        movements
                                                      • Painful bowel
                                                        movements
                                                      • Gas
                                                      • Diarrhea
                                                      • Constipation
                                                      • Increased mucus
                                                        production

                   ©Jeff Lavell, DC

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                                            •IBS is the most frequent GI disorder and
                                            accounts for 30-50% of all referrals to
                                            gastroenterologists.
                                               • Poorly understood
                                               • It is believed to affect approximately one-
                   Incidence                     fifth of the population, though it is
                                                 estimated that 60-75% of symptomatic
                                                 people do not seek medical attention
                                                                  • Source: Madden JAJ, Hunter JO.
                                                                    Br J Nutr 2002; 88(Suppl 1): S67-
                                                                    S72

©Jeff Lavell, DC

                   IBS Classification Systems

                     IBS‐D                  IBS‐C                                 IBS‐A
                            Diarrhea              Constipation
                       predominates and        predominates and                        Alternating
                         often relieves        bowel movement                        constipation &
                      symptoms, increased        often relieves                         diarrhea
                             mucus                 symptoms

                                               ©Jeff Lavell, DC

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                                             Magnesium and IBS‐C
                                             • What Does the Research Say?
                                             • Magnesium does have a well-established reputation for its
                                               laxative qualities. However, there does not appear to be any direct
                                               research support for the use of magnesium as a treatment for IBS-C.
                                             • Of interest is a study that looked at the relationship between
                                               constipation and water, fiber, and magnesium intake. The study was
                                               conducted in Japan with 3,835 subjects who were between the ages of
                                               18 and 20. Constipation was not found to be associated with low fiber
                                               intake or low intake of water from fluids. Constipation was,
                                               however, associated with low intake of magnesium and low intake of
                                               water from foods.
                                             • The laxative effect of magnesium appears to come through two different
                                               mechanisms. Magnesium relaxes the muscles in the intestines, which
                                               helps to establish a smoother rhythm. Magnesium also attracts water.
                                             • The increased amount of water in the colon serves to soften the stool,
                                               helping to make stools easier to pass.
                                                  ©Jeff Lavell, DC

        Psychological
         Symptoms
•Anxiety and/or depression frequently
accompany IBS symptoms to varying
degrees.
•If you have good patient rapport:
      • Ask about psychological stress
      • Make an appropriate referral
      • Make nutritional recommendations
        consistent with stress alleviation

                                                  ©Jeff Lavell, DC

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IBD

©Jeff Lavell, DC

                     Dysbiosis
                     Defined

                   • Round JL, Mazmanian SK. The gut
                     microbia shapes intestinal immune
                     responses during health and
                     disease. Nat Rev Immunol. 2009
                     May, 9(5):313‐23

©Jeff Lavell, DC

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  IBS vs IBD
                                IBD                             IBS
  Symptoms                      Eye inflammation                Abdominal pain
                                Extreme fatigue                 Cramps
                                Intestinal scarring             Constipation
                                Joint pain                      Diarrhea
                                Malnutrition                    Bowel urgency
                                Rectal bleeding
                                Weight loss
                                Bowel urgency

  Testing                       Extensive lab work              Normal labs
                                Abnormal tissue biopsy          Normal tissue biopsy
  Other                         Autoimmune component            No autoimmune component

                                             ©Jeff Lavell, DC

Deviations in human gut microbiota: a novel diagnostic
test for determining dysbiosis in patients with IBS or IBD.

       RESULTS:
       • Validation confirms microbiota dysbiosis was detected in 73%
         of IBS patients, 70% of treatment‐naïve IBD patients and 80%
         of IBD patients in remission, vs. 16% of healthy individuals.

             • Source: Aliment Pharmacol Ther. 2015 Jul;42(1):71‐83.
               Deviations in human gut microbiota: a novel diagnostic test for
               determining dysbiosis in patients with IBS or IBD. Casén C et. al.

                                             ©Jeff Lavell, DC

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                                           •The long‐standing assumption that ulcerative
                                           colitis (UC) is an autoimmune disease has been
                                           revised to incorporate evidence suggesting that
                                           commensal microflora and their products are
                                           auto‐antigens, and that UC is caused by loss of
                                           tolerance towards otherwise harmless
IBD Autoimmune and                         components of the normal intestinal flora.
     microflora                                  • Source: Farrell RJ, Peppercorn MA. Lancet 2002;
                                                   359(9303): 331‐340

                                                         • Slide courtesy of Kerry Bone

                                            ©Jeff Lavell, DC

 Further evidence of dysbiosis
 •UC and Dysbiosis
     • Compared to healthy people, UC patients have increased levels of IgG directed against the
       normal flora1
     • There may be an increased number of bowel bacteria in UC, but reduced counts of protective
       bacteria such as Lactobacilli and Bifidobacteria1
     • Lactobacilli numbers were found to be lower in UC patients during the active phase
         • Sources:
             • Cummings JH, Macfarlane GT, Macfarlane S. Curr Issues Intest Microbiol 2003; 4(1):
                9‐20
             • Bullock NR, Booth JC, Gibson GR. Curr Issues Intest Microbiol 2004; 5(2): 59‐64

                                            ©Jeff Lavell, DC

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• Gut dysbiosis
• These same factors may also play a major role in the
  development of Type I diabetes.
    • Researchers found that by simply providing
      probiotics to animals with altered gut flora they
      could reduce the incidence of the disease.

              • Source: The “Perfect Storm” for Type 1
                Diabetes The Complex Interplay Between
                Intestinal Microbiota, Gut Permeability,
                and Mucosal Immunity. Outi Vaarala,
                Mark A. Atkinson, Josef Neu. Diabetes
                October 2008 vol. 57 no. 10 2555‐2562

Clinical Note
                                                    ©Jeff Lavell, DC

                                                •    There is suggestion that the misfolding of
                                                     proteins in the brain may be an etiologic
                                                     explanation for some neurologic disorders. Brain
                                                     inflammation, which may originate from the gut,
                                                     is one notable hypothesis behind protein
                                                     misfolding.
    Misfolding of
                                                          •
  Proteins Linked                                                Source: De Theije CG, Wu J, da Silva SL, et
                                                                 al. Pathways underlying the gut‐to‐brain
         to Gut?                                                 connection in autism spectrum disorders
                                                                 as future targets for disease
                                                                 management. Eur J Pharmacol. 2011;668
                                                                 Suppl 1:S70‐S80.
                                                          •      Source: Soto C. Unfolding the role of
                                                                 protein misfolding in neurodegenerative
                                                                 diseases. Nat Rev Neurosci. 2003;4:49‐60.

                                                    ©Jeff Lavell, DC

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Gut Health & Neurodegeneration

                                                                  It appears that age-related changes in
                                                                  the gut microbiota might be
  Brain-derived neurotrophic factor, a                            bidirectionally linked to age-related
     neurotrophin that protects and                               neurodegeneration.[4]
 encourages survival of healthy brain                             • Connor B, Young D, Yan Q, Faull RL, Synek B,
  cells and whose production may be                                 Dragunow M. Brain-derived neurotrophic factor is
influenced by gut bacteria, is shown to                             reduced in Alzheimer's disease. Brain Res Mol
                                                                    Brain Res. 1997;49:71-81. Abstract
be decreased in people with Alzheimer
                                                                  • Friedland RP. Mechanisms of molecular mimicry
              disease.[3]                                           involving the microbiota in neurodegeneration. J
                                                                    Alzheimers Dis. 2015 Jan 13. [Epub ahead of
                                                                    print]

                                              ©Jeff Lavell, DC

                                      Sulfide bacteria

             •UC and SRB (sulfide reducing bacteria)
                  • In patients with active UC, there is an over‐production of hydrogen
                    sulfide which is toxic to the intestinal mucosa by competing with
                    short‐chain fatty acids (SCFA)1
                  • This appears to be due to an excess (or greater activity) of sulfate‐
                    reducing bacteria (SRB): such as Desulfibrio desulfuricans 1

                                               ©Jeff Lavell, DC

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                                                               • Patients advised to avoid nuts,
     Dietary                                                     garlic, onions, red meat, and
Recommendations‐                                                 cruciferous vegetables.
  Low sulfur diet                                                  • Source: Roediger WE. Lancet
                                                                     1998; 351(9115): 1555

                                            ©Jeff Lavell, DC

      IBD Differential Diagnosis:
      Crohn’s vs. ulcerative colitis
      Crohn's Disease                                 Ulcerative Colitis

      Patchy areas of inflammation                    Continuous inflammation
      Linear and serpiginous (snake‐like)
      ulcers                                          Continuous ulceration

      Depth of inflammation varies: may be
      transmural & deep into tissues
                                                      Depth of inflammation is shallow &
                                                      mucosal in UC
      Fistulae (abnormal passageways
      between organs) commonly seen in                Fistulae seldom seen in UC
      Crohn’s

                                            ©Jeff Lavell, DC

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  Diet may contributes to these poor functional response and status

                                                                    ©Jeff Lavell, DC
                                                                                       Sartor and Mazmanian. Am J Gastroenterol Suppl (2012) 1:15–21

     North and South Relationship
Abstract
OBJECTIVE:
Bile acids are derived from cholesterol and are potent physiological laxatives. The aim of this study was to investigate whether bile acid
synthesis is altered in constipation.
MATERIAL AND METHODS:
Female patients with constipation (23 IBS‐C, 4 functional constipation (FC)) were studied and compared with non‐constipated subjects (16
IBS‐D, 20 healthy women). Body mass index (BMI), blood lipids, lanosterol, sitosterol, colonic transit (oro‐anal transit time (OATT),
reference < or =4.3 days) and stool frequency were measured. C4 (7‐alpha‐hydroxy‐4‐cholesten‐3‐one) levels reflecting bile acid synthesis
were measured at 0800 h and 1300 h.
RESULTS:
When all the groups of constipated and non‐constipated subjects were compared, it was found that only stool frequency and OATT
differed between groups (p
3/29/2021

        Quest Diagnostics: Available Tests for the Differential
        Diagnosis and Management of Inflammatory Bowel Disease
Test Code   Test Name                                                                        Specimen Type   Clinical Use
70171       ANCA Screen with Reflex to ANCA Titer                                            Serum           Diagnose IBD; differentiate UC and CD
            Includes titer for C‐ANCA, P‐ANCA, and/or atypical P‐ANCA.
16796       Calprotectin, Stool                                                              Stool           Diagnose intestinal inflammation; differentiate
                                                                                                             IBD from IBS; monitor patients with IBD
4420        C‐Reactive Protein (CRP)                                                         Serum           Detect inflammatory disorders, including IBD;
                                                                                                             monitor patients with IBD
16503(X)    Inflammatory Bowel Disease Differentiation Panel                                 Serum           Diagnose IBD; differentiate UC and CD;
            Includes ANCA screen with reflex to P‐ANCA,C‐ANCA, and atypical P‐ANCA titers;                   differentiate IBD from vasculitides
            myeloperoxidase antibody; proteinase 3 antibody; and Saccharomyces
            cerevisiae IgG and IgA antibodies.
17321(X)    Lactoferrin, Quantitative, Stool                                                 Stool           Diagnose intestinal inflammation; differentiate
                                                                                                             IBD from IBS; monitor patients with IBD
8796        Myeloperoxidase Antibody (MPO)                                                   Serum           Differentiate IBD from vasculitides
34151       Proteinase‐3 Antibody                                                            Serum           Differentiate IBD from vasculitides
10295       Saccharomyces cerevisiae Antibodies (ASCA) (IgA)                                 Serum           Differentiate UC and CD
17609       Saccharomyces cerevisiae Antibodies (ASCA) (IgA, IgG)                            Serum           Differentiate UC and CD
10294       Saccharomyces cerevisiae Antibodies (ASCA) (IgG)                                 Serum           Differentiate UC and CD
809         Sed Rate by Modified Westergren                                                  Whole blood     Detect inflammatory disorders, including IBD

                                                                      ©Jeff Lavell,
                                                      *UC: Ulcerative Colitis,   CD:DC Crohn’s Disease

                                                                    Abstract
                                                                    • AIM: To investigate patient‐reported outcomes
                                                                      from, and adherence to, a low FODMAP diet
                                                                      among patients suffering from irritable bowel
          FODMAP                                                      syndrome and inflammatory bowel disease.
                                                                    • CONCLUSION: These data suggest that a diet low
        Diet For IBS                                                  in FODMAPs is an efficacious treatment solution
          and IBD?                                                    in the management of functional bowel
                                                                      symptoms for IBS and IBD patients.

                                                                           • World J Gastroenterol. 2016 Apr 21;22(15):
                                                                             Follow‐up of patients with functional bowel
                                                                             symptoms treated with a low FODMAP diet.
                                                                             Maagaard L1, Ankersen DV1, Végh Z1, Burisch
                                                                             J1, Jensen L1, Pedersen N1, Munkholm P1.

                                                                               ©Jeff Lavell, DC

                                                                                                                                                                     42
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                   Further Evidence
        • Int J Mol Med. 2012 May;29(5):723‐31. doi: 10.3892/ijmm.2012.926. Epub 2012 Feb 24.
        • The role of diet in the pathogenesis and management of irritable bowel syndrome (Review).
        • El‐Salhy M1, Ostgaard H, Gundersen D, Hatlebakk JG, Hausken T.
        Abstract
        • Most patients with irritable bowel syndrome (IBS) believe that diet plays a significant role in inducing IBS symptoms
          and desire to know what foods to avoid. It has been found that the intake of calories, carbohydrates, proteins and
          fat by IBS patients does not differ from that of the background population. IBS patients were found to avoid certain
          food items that are rich in fermentable oligo‐, di‐ and monosacharides and polyols (FODMAPs), but they did have a
          high consumption of many other FODMAP‐rich food items. The diet of IBS patients was found to consist of a low
          calcium, magnesium, phosphorus, vitamin B2 and vitamin A content. There is no consistent evidence that IBS
          patients suffer from food allergy, nor is there documented evidence that food intolerance plays a role in IBS
          symptoms. Abnormalities in gut hormones have been reported in IBS patients. As gut hormones control and
          regulate gastrointestinal motility and sensation, this may explain the abnormal gastrointestinal motility and visceral
          hypersensitivity reported in these patients. Guidance concerning food management which includes individually
          based restrictions of FODMAP‐rich food items and individual evaluation of the effects of protein‐, fat‐ and
          carbohydrate‐rich/poor diets may reduce IBS symptoms.
                                                               ©Jeff Lavell, DC

                      Nutritional
                    Considerations

©Jeff Lavell, DC

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                                    •Apples and pears contain pectins
                                        • Pectins are a family of complex
                   Demulcent              polysaccharides

                   Foods            •Okra is a mucilage fiber
                                        • Mucilaginous plants have the characteristic
                                          "goo" or slime

©Jeff Lavell, DC

                                  •Related to colon (large intestine) function
                                      • Diffuse lumbar pain – may radiate into the groin or
                                        lower abdomen
                                      • Constipation and/or diarrhea
                                      • Toxic bowel
                       Clinical       • Flatulence – gas forming organisms will only thrive
                                        in an alkaline GI medium
                   Correlations       • Headaches
                                      • TFL painful on palpation
                                      • Palpation tenderness over the colon
                                      • Transverse process of L4 nodular and tender
                                      • L4 joint dysfunction

                                       ©Jeff Lavell, DC

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                                    •Herbs such as: Boswellia, Celery Seed, Ginger, and
                                    Turmeric are supportive of any chronic inflammatory
                                    disease such as I.B.S., Crohn’s disease, Ulcerative
                                    colitis, and arthritis.
                     Boswellia
                                       • Celery seeds facilitate the clearing out of acidic
                                         waste products in the joints.

                                         ©Jeff Lavell, DC

                   Gut Dysbiosis Functional Nutrition Treatment

©Jeff Lavell, DC

                                                                                                    45
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                                                        ©Jeff Lavell, DC

Coconut Oil & Gut Health
• The saturated fats in coconut oil have anti‐microbial
  effects
• Contains lauric, capric and caprylic acids which are
  known to be anti‐viral.
• It also has been shown to be anti‐fungal, affecting both
  Candida and Malassezia. 1
• By helping to destroy the pathogenic bacteria and
  fungus it is documented by research to improve overall
  gut health.

    • Rial SA, Karelis AD, Bergeron K‐F, Mounier C. Gut
      Microbiota and Metabolic Health: The Potential
      Beneficial Effects of a Medium Chain Triglyceride Diet in
      Obese Individuals. Nutrients. 2016;8(5):281.

                                                        ©Jeff Lavell, DC

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              Dietary medium chain triglycerides (MCT),
              which have been found to promote lipid
              catabolism, energy expenditure and weight
              loss also have an ability to improve both
              intestinal microbiome and permeability.

Coconut Oil
              “MCT‐enriched diets could therefore be used
and Obesity   to manage metabolic diseases through
              modification of gut microbiota.”

              • Source:Rial SA, Karelis AD, Bergeron K‐F, Mounier C. Gut
                Microbiota and Metabolic Health: The Potential
                Beneficial Effects of a Medium Chain Triglyceride Diet in
                Obese Individuals. Nutrients. 2016;8(5):281.

              ©Jeff Lavell, DC

              A number of studies have shown promise when it
              comes to coconut oil.

              Lipids. 2009 Jul;44(7):593‐601.Effects of dietary
              coconut oil on the biochemical and anthropometric
Coconut Oil   profiles of women presenting abdominal obesity.
              • This study showed 40 women were given either 30 grams (2
and Weight      tablespoons) of either coconut oil or soybean oil for 28 days.They
                were instructed to eat fewer calories and walk every day. These

Loss            were the results:
                • Both groups lost weight (about 2 pounds).
                • Only the coconut oil group had decreased waist circumference
                  (belly fat) while the soybean oil actually had a mild increase in
                  belly fat. Coconut oil did not cause overall weight loss compared
                  to soybean oil, but it did lead to a significant reduction in belly
                  fat.
                • The coconut oil group had increased HDL (good) cholesterol
                  levels, while the soybean oil had reduced HDL and increased LDL.

              ©Jeff Lavell, DC

                                                                                              47
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                 ISRN Pharmacol. 2011;2011:949686. Epub
                 2011 Mar 15.An open‐label pilot study to
                 assess the efficacy and safety of virgin
                 coconut oil in reducing visceral adiposity.
                 Liau KM1, Lee YY, Chen CK, Rasool AH.
Coconut Oil
and
                 In this second study this time involving
Weightloss       obese men:

                 • 30 grams of coconut oil (2 tablespoons) for 4 weeks
                   reduced waist circumference by 2.86 cm, or 1.1
                   inches

                ©Jeff Lavell, DC

              Whereas the primary fuel source for the energy‐hungry brain is
              glucose, when insulin resistance and suboptimal metabolism
              (hypometabolism) develops in the brain, both the brain's structure
              and function are compromised. Ketone bodies provide a much
              needed alternative fuel source to glucose that can recharge
              metabolic processes within the brain, resulting in an almost
              immediate improvement in cognitive function. (1)

Coconut Oil   They are preferentially oxidized by the liver, and when provided in
              large enough quantities, they give rise to ketone bodies. Due to
              their smaller size they do not form micelles and are not stored in
              adipose tissue. (2)

              • Source: Effects of beta‐hydroxybutyrate on cognition in memory‐impaired
                adults. Neurobiol Aging. 2004 Mar;25(3):311‐4. Mark A Reger, Samuel T
                Henderson, Cathy Hale, Brenna Cholerton, Laura D Baker, G S Watson, Karen Hyde,
                Darla Chapman, Suzanne Craft.
              • Source: Hypometabolism as a therapeutic target in Alzheimer's disease. BMC
                Neurosci. 2008 ;9 Suppl 2:S16. Epub 2008 Dec 3. Lauren C Costantini, Linda J Barr,
                Janet L Vogel, Samuel T Henderson.

                ©Jeff Lavell, DC

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           Avoid Gut Wrecking Foods
               • The types of food choices that threaten the bacteria are foods:
                   1. Low in fiber
                   2. High in simple sugars
                   3. Foods that contain artificial sweeteners.

                          •    Source: Brain Maker: The Power of Gut Microbes to Heal and
                               Protect Your Brain–for Life. David Perlmutter Little, Brown, Apr 28,
                               2015

                                                ©Jeff Lavell, DC

Bowel & Immunity

• The gut is constantly exposed to a high antigenic load coming from the diet
  and commensal bacteria.
    • The Gut-Associated Lymphoid Tissue (GALT) constitutes the most
      extensive and complex part of the immune system and is capable of
      efficiently distinguishing invasive pathogens from innocuous antigens.
                  • Source: Ramiro-Puig E, Pérez-Cano FJ, Castellote C,
                    Franch A, Castell M. [The bowel: a key component of the
                    immune system]. [Article in Spanish]. Rev Esp Enferm Dig.
                    2008 Jan;100(1):29-34.

                                                ©Jeff Lavell, DC

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                   Gut Chemicals
                   •   Imbalances of gut bacteria can lead to the breakdown of the lining of the gut so that
                       chemicals, like Lipopolysaccharides (LPS), that should stay in the gut get into the
                       systemic circulation and amplify inflammation.

                   •   Bacterial-derived lipopolysaccharides (LPS) play an essential role in the inflammatory
                       process of inflammatory bowel disease. A defective intestinal tight junction (TJ) barrier
                       is an important pathogenic factor of inflammatory bowel disease and other inflammatory
                       conditions of the gut.

                   • Source: Lipopolysaccharide Causes an Increase in Intestinal Tight Junction
                     Permeabilityin Vitro and in Vivo by Inducing Enterocyte Membrane Expression and
                     Localization of TLR-4 and CD14. Am J Pathol. 2013 Feb; 182(2): 375–387. Shuhong
                     Guo,∗† Rana Al-Sadi,∗† Hamid M. Said,‡ and Thomas Y. Ma

                                                            ©Jeff Lavell, DC

                                                      • Gut Barrier Components:
                                                          • Lumen
                                                              • Commensal Bacteria
                                                          • Tight Junctions
                                                              • Intestinal epithelial cells
                                                              • Occludin family of peptides (see figure previous
      Altered Intestinal                                        slide)
               Immune                                     • GALT
      Responsiveness                                          • Mucosal barrier cells
                                                              • M-cells
                                                              • Goblet cells
                                                              • Paneth cells
                                                              • Intraepithelial lymphocytes

©Jeff Lavell, DC

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GALT & Leaky
Gut
• Too much intestinal permeability
(Leaky Gut) causes GALT to
generate more Immunoglobulins
(secretory IgA in particular) in
response to foreign proteins.

                                     ©Jeff Lavell, DC

                                             • Pathogenic and commensal
                                               microbes in the gut can mimic the
                                               cell surface molecules of the host to
                                               pass through the tight junctions of
                                               the gut and gain access to the body
  Molecular Mimicry                              • Once inside this results in
                                                   systemic changes that may be
                                                   detrimental to ones health, just
                                                   like the previous slide with celiac.

                                     ©Jeff Lavell, DC

                                                                                                51
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                                 • Cross-reactivity is the reaction
                                   between an antigen and an antibody
                                   which was generated against a
                                   different but similar antigen
                                     • Because of molecular mimicry,
                                       the immune system can mount
 Cross Reactivity                      an immune response against its
                                       own tissues.
                                         • Modulating an over zealous
                                           immune response is
                                           necessary
                                         • Reducing the flow of antigens
                                           across the gut is imperative!

                         ©Jeff Lavell, DC

Identify and remove Most Common gut
allergens:

01             02                     03               04
Corn           Wheat/gluten           Soy              Milk/Dairy

                         ©Jeff Lavell, DC

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    Gut Allergens Masquerade as
             GI Disease
• Before making any specific supplemental suggestions it is
  best to:
    • Eliminate allergens that can mimic GI disease and cause
      confounding results.
    • Use an elimination diet for 2-3 weeks to rule out the Main
      Four Allergens as the source of digestive problems.

                           ©Jeff Lavell, DC

                                                              Leaky Gut

                            ©Jeff Lavell, DC

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“A ballooned colon will
   certainly let poisons
          pass into the                           ‐Royal Lee 1959
 circulating blood that
    an intact colon will
                   stop”
                               ©Jeff Lavell, DC

Lower GI pathophysiology
•Pathophysiology related to Gut
Permeability – i.e. permeability of tight
junctions (aka “leaky gut”).
   • The gut regulates the absorption of
     many nutrients based on the
     permeability of the tight junctions
     (spaces between cells).
   • Most gut conditions have some
     involvement of a leaky gut.

                               ©Jeff Lavell, DC

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                                   ©Jeff Lavell, DC

Etiology
Three factors play a role in the
 development of Leaky Gut:
   1. Aberrant intestinal
        microbiota
   2. Loss of mucosal integrity
   3. Altered intestinal
        immune responsiveness

                                   ©Jeff Lavell, DC

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             Clinical Note
          These same factors may also play a
          major role in the development of Type
          I diabetes.
                   • Researchers found that by simply
                     providing probiotics to animals
                     with altered gut flora they could
                     reduce the incidence of the
                     disease.

                       •   Source: The “Perfect Storm” for Type 1
                           Diabetes The Complex Interplay Between
                           Intestinal Microbiota, Gut Permeability, and
                           Mucosal Immunity. Outi Vaarala, Mark A.
                           Atkinson, Josef Neu. Diabetes October
                           2008 vol. 57 no. 10 2555-2562                  ©Jeff Lavell, DC

                    Signs/Symptoms

©Jeff Lavell, DC

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                                                      Leaky Gut Syndrome has
                                                        been linked with many
                                                        conditions:
Leaky Gut &                                               • Celiac Disease
Other                                                     • Multiple Sclerosis
                                                          • Fibromyalgia
Conditions                                                • Autism
                                                          • Chronic Fatigue
                                                            Syndrome
                                                          • Irritable Bowel
                                                            Syndrome
                                                          • Eczema
                                                          • Dermatitis
                                                          • Ulcerative Colitis

                                   ©Jeff Lavell, DC

 Medical Treatment Model
 • Leaky Gut is not a recognized diagnosis in the medical
   profession
     • Often misdiagnosed as an intestinal infection or an
       inflamed gut
     • Often mismanaged with medications that actually
       worsen the condition by causing more dysbiosis. For
       example:
         • Antibiotics
         • Steroids
         • Anti‐inflammatory drugs
         • Colectomy

                                   ©Jeff Lavell, DC

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                                      • Gut Barrier Components Affected by Intestinal
                                        Permeability:
                                         • Lumen
       Altered                               • Commensal Bacteria
     Intestinal                          • Tight Junctions
                                             • Intestinal epithelial cells
      Immune                                 • Occludin family of peptides (see figure previous
Responsiveness                           • GALT
                                               slide)

                                             • Mucosal barrier cells
                                             • M‐cells
                                             • Goblet cells
                                             • Paneth cells
                                             • Intraepithelial lymphocytes

                                           ©Jeff Lavell, DC

                                                                           Leaky Gut

      NSAIDs &
      Leaky Gut
                                                                                               Chemical
                                                Consumption
                                                                                               and Food
                                                 of NSAIDs
                                                                                              Sensitivites

 Intensity of pan and complications
   increase with each repetition of
               the cycle
                                                                                       Histamine
                                                              Worse Pain
                                                                                        Release

                                           ©Jeff Lavell, DC

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            Leaky Gut Testing
• LOW secretory IgA is associated with leaky gut. Look
                  for this in the labs!

                       ©Jeff Lavell, DC

       IGG/IGA testing:
         Cyrex Labs

                       ©Jeff Lavell, DC

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   ELISA/EIA (Enzyme Immunoassays) panels

   • IgG testing is based on the findings that certain subclasses of IgG have been associated
     with the in vitro degranulation of basophils and mast cells, the activation of the
     complement cascade, (both of which are important mechanisms in allergy and
     anaphylaxis) and the observation that high circulating serum concentrations of some IgG
     subtypes have been measured in certain atopic individuals.
       • Source:
           • Berry, J.B., and Brighton, W.D. Familial human short term sensitizing (IgG S‐TS) antibody. Clin
              Allergy 1977; 7:401‐406.
           • Parish, W.E., Short term anaphylactic IgG antibodies in human sera. Lancet 1970; ii:591‐2.
           • Stanworth, D.R., Immunochemical aspects of human IgG4. Clin. Rev. Allergy 1983; 1:183‐95.
           • Brighton, W.D., Frequency of occurrence of IgG (S‐TS). Clin. Allergy 1980; 10:97‐100.
           • Wintroub, B.U., and Soter, N.A., Biology of the mast cell and its role in cutaneous inflammation.
              Springer Semin. Immunopathol. 1981; 4:55.

                                                 ©Jeff Lavell, DC

                                         • The Intestinal Permeability
                                           Assessment gastrointestinal test directly measures
                                           the ability of two non-metabolized sugar molecules to
                                           permeate the intestinal mucosa. The patient drinks a
Genovea: Gut                               premeasured amount of lactulose and mannitol. The
                                           degree of intestinal permeability or malabsorption is
 Permability                               reflected in the levels of the two sugars recovered in a
                                           urine sample collected over the next 6 hours.
                                         • Used for leaky gut (urine test)
                                         • Great test as it is done at home by the patient!

                                                ©Jeff Lavell, DC

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Lab Tests
•CDSA – Genova Diagnostics
   • The Comprehensive
     Digestive Stool Analysis
     provides diagnostic tools
     for analysis of digestion,
     colonic environment and
     absorption.

                                            ©Jeff Lavell, DC

    Leaky Gut Trick

    • 1500 mg pure GABA if they get
      tired/sleepy within 30 minutes that
      is an indicator of leaky gut due to
      poor gut membrane junctions.

                                            ©Jeff Lavell, DC

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                       Therapeutic Goals:
                          A. Reduce systemic allergic reactions
Functional                B. Improve immune competence &
                              regulation
Treatment                 C. Normalize bowel function
  Strategy                   • Chiropractic
                             • Allergen identification & elimination diet
                          D. Balance gut flora

                            ©Jeff Lavell, DC

 A. Reduce Systemic Allergic
 Reactions

            Avoid the allergen
  Avoid     • IgG [ELISA/EIA (Enzyme Immunoassays) panels] testing
              can be helpful, but the tests are very expensive

 Improve Improve hepatic clearance of antigenic material

                            ©Jeff Lavell, DC

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