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GUT HEALTH AND SYSTEMIC DISEASE
Your gut holds the keys to optimal health
Keith R. Holden, M.D.
FOOD SENSITIVITY & SYSTEMIC COMPLAINTS
GUT INFLAMMATION & SYSTEMIC DISEASE
 Total surface area of GI tract > 200X surface area
of skin
 GI tract is the largest surface area where we
interact with our environment
 Gut immune dysregulation + excessive
inflammation = systemic disease
GUT FUNCTION & AUTOIMMUNE DISEASE
 Environmental triggers (food, microbes)
 Genetic tendency for immune system to overreact
to triggers
 Intestinal hyperpermeability associated with many
diseases – CD, T1DM, MS, RA, IBD
CELIAC DISEASE – CLUES FOR AUTOIMMUNITY
 TRIAD
 1) Environmental trigger (antigen, e.g. gluten)
 2) Genetic susceptibility (HLA pattern particularly
efficient at presenting antigen (gluten) to immune cells
(HLA-DQ2/HLA-DQ8)
 3) Intestinal hyperpermeability AKA “leaky gut” – tight
junctions moderated by specific proteins
Fasano A. Sci Am. August 2009;301(2):54-61
ALESSIO FASANO, M.D.
Prof. of Pediatrics & Dir. of Ctr. for Celiac Disease
Research at Univ. of Maryland School of Med.
 “Together with the gut-associated lymphoid tissue
and the neuro-endocrine network, the intestinal
barrier, with its tight junctions, controls the
equilibrium between tolerance and immunity to
nonself-antigens. When the finely tuned trafficking
of macromolecules is dysregulated in genetically
susceptible individuals, both intestinal and
extraintestinal autoimmune disorders can occur.”
HELICOBACTER PYLORI
 Most common chronic bacterial inf. in the world
 Present in half of world’s population
 Affinity for stomach mucosa
 Disrupts permeability of GI tract
 Induces a sustained immune response (excess
inflammation)
 May progress from gastritis to malignancy
 Molecular mimicry results in systemic AD
MOLECULAR MIMICRY (MISTAKEN IDENTITY)
 Environmental exposure to antigens (food,
microbes)
 In genetically susceptible individuals induces cross-
reaction with structurally similar AA motifs in tissue
 CD patients have ~ 10X rate of autoimmune thyroid
disease as nonceliacs reflective of gluten/gliadin
Ag-Ab complexes for thyroid tissue
H. PYLORI & SYSTEMIC DISEASE
 IHD
 CVD
 ITP
 Iron-deficiency anemia
 Idiopathic anterior uveitis
 Autoimmune thyroid disease (Graves, Hashimotos)
 MALT lymphoma
BACTERIAL ASSOC. WITH SYSTEMIC DISEASE
 Klebsiella penumoniae – spondyloarthritis (AS)
 Yersinia enterocolitica – autoimmune thyroid dis.
 Campylobacter jejuni – reactive arthritis, GBS
 Salmonella – reactive arthritis
 E. coli – HUS
 Candida albicans – atopic dermatitis, CD
 Strep pyogenes – Rheumatic Fever
 Chlamydia – MS
 Citrobacter, Klebsiella, Proteus - RA
SUMMARY
 Studies are showing that the triad of
(1)environmental triggers (food, microbes),
(2)genetic susceptibility, and (3)intestinal
hyperpermeability play a key role in the
development of autoimmune and other systemic
diseases through uncontrolled inflammation.
 Other issues: digestion and proper assimilation of
micronutrients necessary for optimal immune
status; beneficial bacteria’s role in digestion and
immunity; and the gut-brain axis
GUT-BRAIN AXIS
MY APPROACH
 Comprehensive History & Physical
 Antecedents and Triggers
 Detoxification Questionnaires
 Toxin exposure history (past and present)
 Signs and symptoms of micronutrient deficiencies
 Signs and symptoms of “leaky gut” & dysbiosis
 Review of bowel habits in detail
 Detailed physical exam
DETAILED ORODENTAL ASSESSMENT
 Plaque, amalgams, crowns, bridges
(malocclusion?)
 Mixed metals (galvanism)
 Old root canals (notorious for infection)
 TMJ (CST, chiropractor)
 Tongue, gums, mucous membranes, tonsils
MEDICATION REVIEW
 Culprits for “leaky gut,” micronutrient deficiencies,
and microbial overgrowth:
 PPI, H2 blockers, antacids
 NSAIDS
 Corticosteroids
 Statins (CoQ10)
 Antibiotics
NUTRITIONAL ASSESSMENT
 Dietary review
 Standard American Diet (SAD)
 FM Comprehensive Elimination Diet – stress
elimination of wheat/gluten, dairy, sugar, high-
glycemic index foods (grains), caffeine, ETOH
ALCAT
 Measures the change in WBCs in size and number after
antigen exposure
 Screens for reactivity to foods, additives, colorings,
drugs, and molds
ALCAT AND WEIGHT LOSS
 “Even when one focuses only on the changes
occurred in the experimental group without
comparison to the control group, the data reveal
that 98 percent of the subjects following the ALCAT
plan either lost scale weight or improved body
composition.”
Kaats GR, Pullin DP, Parker KL. The short term efficacy of the
ALCAT test of food sensitivities to facilitate changes in body
composition and self-reported disease symptoms: a
randomized controlled study. The Bariatrician. Spring 1996.
PRIORITY TESTING – CDSA/PARASITOLOGY
 CDSA with microbial stool analysis including
parasitology and H. pylori screening
 Assesses for dysbiosis – imbalance of beneficial to
potentially pathogenic microbes
 Some assess for inflammatory markers, bile salts,
HCL status, and pancreatic enzyme function
 Does not assess for SIBO
5 RS OF FUNCTIONAL MEDICINE
 Remove
 Replace
 Repair
 Reinoculate
 Rebalance
REMOVE (STRESSORS)
 Biomechanical imbalance/subluxation
 Address stress including old emotional toxins
 Food sensitivities (FM CED, ALCAT)
 Detoxify xenobiotics (ext. toxins) and endotoxins
 Pathogenic microbes (bacteria, yeast, parasites)
REPLACE
 HCL
 Digestive enzymes
 Bile salts
 Fiber
REPAIR
 Rest
 Vitamins (pantothenate, E, A, D, C)
 Activated B vitamins (pyridoxal 5 phosphate, folinic
acid/L-methylene tetrahydrofolate,
methylcobalamin/adenosycobalamin)
 Minerals (zinc)
 Support of GALT fxn (lactoferrin, whey, Ig)
 Antioxidants (catechins)
 Anti-inflammatories (curcumin, EPA/DHA/GLA/oleic
acid)
 Glutamine and aloe vera
REINOCULATE (BENEFICIAL FLORA)
 Probiotics (Bifidobacter, Lactobacillus, S. boulardii)
 Prebiotics (Inulin, FOS, Arabinogalactan)
REBALANCE
 Lifestyle changes
 Scheduling rest and relaxation; adequate sleep
 Mindful eating
 Balance autonomic nervous system
 Balance brain waves
BASIC NUTRITIONAL SUPPLEMENTS
 High potency MVI/MM w/aBv – Prothera MultiThera
 Activated B vitamins – NeuroBiologix Neuro-Immune
Stabilizer (transdermal)
 Essential Fatty Acids blend (EPA/DHA 3000mg) –
Natura Health Products Beyond Essential Fats
 Probiotics 25-900 bil cfu (Ther-Biotic Complete, VSL#3)
 Vitamin D (based on blood levels)
 Medical Food (Xymogen I5)
REMOVE
 DFH GI MicrobX or Prothera Undecylex
 Parasites: BioPure Artemesinin or Mimosa Pudica
 Bacterial: Syntrion SyGest + SanPharma Firmus
 Fungal: Syntrion SyRegule + SanPharma Candida-
Roqueforti suppositories
 Fungal Sinus: Syntrion SyFungin & Argentyn 23 NS
 PEKANA Mucan, Helmin, Opsonot, Mundipur
 Natural Immunogenics Argentyn 23 liquid/spray
 Detoxification: PEKANA Basic Detoxification &
Drainage Kit (apo-Hepat, Renelix, Itires)
 Syntrion SyDetox for “hot liver” signs & symptoms
TREATING H. PYLORI WITHOUT ANTIBIOTICS
 OrthoMolecular Products Pyloricil (Zinc carnosine,
Mastic gum, Berberine, Bismuth citrate) x 2 mos
 Lactoferrin
 Probiotics/Kefir
 Always check H. pylori stool Ag 1 month after
completion of therapy
PARASITE THERAPY
 B. hominis: SMX/TMP + Metronidazole/Secnidazole
 Cryptosporidia: Nitazoxanide (Alinia)
 Dientamoeba fragiis: Iodoquinol
 Enterobius Vermicularis (PW): Pyrantel Pamoate
 Giardia: Tinidazole/Metronidazole
 Entamoeba histolytica: Iodoquinol
 Worms: Albendazole/Mebendazole
 Apothecure pharmacy – Paragone 5 and Paragone 6
(compounded combination of antiparasitics)
REPLACE
 Theramedix DGX
 Betaine HCL
 Standard Process Cholachol
 Natural Factors PGX (konjac root)
REPAIR
 GI Cocktail: 1 heaping tsp of glutamine powder in ½
cup of George’s Aloe Vera juice 2-3 x day
 ECGC (green tea)
 Curcumin
 Xymogen IgG 2000/Xymogen I5
REINOCULATE
 Klaire Labs Ther-Biotic Complete (25 bil CFU)
 VSL#3 (caps 112.5 bil CFU, packets 450 bil CFU,
and DS packets (requires Rx) 900 bil CFU
 Saccharomyces boulardii (C. difficile)
 Thorne Research Arabinex
REBALANCE
 Address emotional toxins - ERT, counseling,
journaling, Inner Child meditation, compassionate
forgiveness
 Balance autonomic nervous system - acupuncture,
meditation, breath work, yoga, Tai Chi, Ballroom
Dancing, PEMF, Microcurrent therapy (CES), Low-
level laser
SPECIALIST REFERRAL LIST
 Biological/Holistic Dentist
 Chiropractor
 Acupuncturist
 Massage Therapist
 Craniosacral Therapist
 Eden Energy Practitioner
 Holistic Psychological Counselors
FINAL ADVICE
 Stay open to possibilities
 See the world through the eyes of a child
 Embrace change
 Take with you what resonates with you and leave
the rest alone (what feels right)
 Never stop evolving (transformation/growth)
MINDFULNESS
“Mindfulness practice means that we commit fully in
each moment to be present; inviting ourselves to
interface with this moment in full awareness, with
the intention to embody as best we can an
orientation of calmness, mindfulness, and
equanimity right here and right now.”
Jon Kabat-Zinn, Wherever You Go, There You Are
ALCAT TEST
Cell Science Systems
852 South Military Trail
Deerfield Beach, Florida 33442
www.alcat.com

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Gut Health and Systematic Disease.

  • 1. GUT HEALTH AND SYSTEMIC DISEASE Your gut holds the keys to optimal health Keith R. Holden, M.D.
  • 2. FOOD SENSITIVITY & SYSTEMIC COMPLAINTS
  • 3. GUT INFLAMMATION & SYSTEMIC DISEASE  Total surface area of GI tract > 200X surface area of skin  GI tract is the largest surface area where we interact with our environment  Gut immune dysregulation + excessive inflammation = systemic disease
  • 4. GUT FUNCTION & AUTOIMMUNE DISEASE  Environmental triggers (food, microbes)  Genetic tendency for immune system to overreact to triggers  Intestinal hyperpermeability associated with many diseases – CD, T1DM, MS, RA, IBD
  • 5. CELIAC DISEASE – CLUES FOR AUTOIMMUNITY  TRIAD  1) Environmental trigger (antigen, e.g. gluten)  2) Genetic susceptibility (HLA pattern particularly efficient at presenting antigen (gluten) to immune cells (HLA-DQ2/HLA-DQ8)  3) Intestinal hyperpermeability AKA “leaky gut” – tight junctions moderated by specific proteins Fasano A. Sci Am. August 2009;301(2):54-61
  • 6. ALESSIO FASANO, M.D. Prof. of Pediatrics & Dir. of Ctr. for Celiac Disease Research at Univ. of Maryland School of Med.  “Together with the gut-associated lymphoid tissue and the neuro-endocrine network, the intestinal barrier, with its tight junctions, controls the equilibrium between tolerance and immunity to nonself-antigens. When the finely tuned trafficking of macromolecules is dysregulated in genetically susceptible individuals, both intestinal and extraintestinal autoimmune disorders can occur.”
  • 7. HELICOBACTER PYLORI  Most common chronic bacterial inf. in the world  Present in half of world’s population  Affinity for stomach mucosa  Disrupts permeability of GI tract  Induces a sustained immune response (excess inflammation)  May progress from gastritis to malignancy  Molecular mimicry results in systemic AD
  • 8. MOLECULAR MIMICRY (MISTAKEN IDENTITY)  Environmental exposure to antigens (food, microbes)  In genetically susceptible individuals induces cross- reaction with structurally similar AA motifs in tissue  CD patients have ~ 10X rate of autoimmune thyroid disease as nonceliacs reflective of gluten/gliadin Ag-Ab complexes for thyroid tissue
  • 9. H. PYLORI & SYSTEMIC DISEASE  IHD  CVD  ITP  Iron-deficiency anemia  Idiopathic anterior uveitis  Autoimmune thyroid disease (Graves, Hashimotos)  MALT lymphoma
  • 10. BACTERIAL ASSOC. WITH SYSTEMIC DISEASE  Klebsiella penumoniae – spondyloarthritis (AS)  Yersinia enterocolitica – autoimmune thyroid dis.  Campylobacter jejuni – reactive arthritis, GBS  Salmonella – reactive arthritis  E. coli – HUS  Candida albicans – atopic dermatitis, CD  Strep pyogenes – Rheumatic Fever  Chlamydia – MS  Citrobacter, Klebsiella, Proteus - RA
  • 11. SUMMARY  Studies are showing that the triad of (1)environmental triggers (food, microbes), (2)genetic susceptibility, and (3)intestinal hyperpermeability play a key role in the development of autoimmune and other systemic diseases through uncontrolled inflammation.  Other issues: digestion and proper assimilation of micronutrients necessary for optimal immune status; beneficial bacteria’s role in digestion and immunity; and the gut-brain axis
  • 13. MY APPROACH  Comprehensive History & Physical  Antecedents and Triggers  Detoxification Questionnaires  Toxin exposure history (past and present)  Signs and symptoms of micronutrient deficiencies  Signs and symptoms of “leaky gut” & dysbiosis  Review of bowel habits in detail  Detailed physical exam
  • 14. DETAILED ORODENTAL ASSESSMENT  Plaque, amalgams, crowns, bridges (malocclusion?)  Mixed metals (galvanism)  Old root canals (notorious for infection)  TMJ (CST, chiropractor)  Tongue, gums, mucous membranes, tonsils
  • 15. MEDICATION REVIEW  Culprits for “leaky gut,” micronutrient deficiencies, and microbial overgrowth:  PPI, H2 blockers, antacids  NSAIDS  Corticosteroids  Statins (CoQ10)  Antibiotics
  • 16. NUTRITIONAL ASSESSMENT  Dietary review  Standard American Diet (SAD)  FM Comprehensive Elimination Diet – stress elimination of wheat/gluten, dairy, sugar, high- glycemic index foods (grains), caffeine, ETOH
  • 17. ALCAT  Measures the change in WBCs in size and number after antigen exposure  Screens for reactivity to foods, additives, colorings, drugs, and molds
  • 18. ALCAT AND WEIGHT LOSS  “Even when one focuses only on the changes occurred in the experimental group without comparison to the control group, the data reveal that 98 percent of the subjects following the ALCAT plan either lost scale weight or improved body composition.” Kaats GR, Pullin DP, Parker KL. The short term efficacy of the ALCAT test of food sensitivities to facilitate changes in body composition and self-reported disease symptoms: a randomized controlled study. The Bariatrician. Spring 1996.
  • 19. PRIORITY TESTING – CDSA/PARASITOLOGY  CDSA with microbial stool analysis including parasitology and H. pylori screening  Assesses for dysbiosis – imbalance of beneficial to potentially pathogenic microbes  Some assess for inflammatory markers, bile salts, HCL status, and pancreatic enzyme function  Does not assess for SIBO
  • 20. 5 RS OF FUNCTIONAL MEDICINE  Remove  Replace  Repair  Reinoculate  Rebalance
  • 21. REMOVE (STRESSORS)  Biomechanical imbalance/subluxation  Address stress including old emotional toxins  Food sensitivities (FM CED, ALCAT)  Detoxify xenobiotics (ext. toxins) and endotoxins  Pathogenic microbes (bacteria, yeast, parasites)
  • 22. REPLACE  HCL  Digestive enzymes  Bile salts  Fiber
  • 23. REPAIR  Rest  Vitamins (pantothenate, E, A, D, C)  Activated B vitamins (pyridoxal 5 phosphate, folinic acid/L-methylene tetrahydrofolate, methylcobalamin/adenosycobalamin)  Minerals (zinc)  Support of GALT fxn (lactoferrin, whey, Ig)  Antioxidants (catechins)  Anti-inflammatories (curcumin, EPA/DHA/GLA/oleic acid)  Glutamine and aloe vera
  • 24. REINOCULATE (BENEFICIAL FLORA)  Probiotics (Bifidobacter, Lactobacillus, S. boulardii)  Prebiotics (Inulin, FOS, Arabinogalactan)
  • 25. REBALANCE  Lifestyle changes  Scheduling rest and relaxation; adequate sleep  Mindful eating  Balance autonomic nervous system  Balance brain waves
  • 26. BASIC NUTRITIONAL SUPPLEMENTS  High potency MVI/MM w/aBv – Prothera MultiThera  Activated B vitamins – NeuroBiologix Neuro-Immune Stabilizer (transdermal)  Essential Fatty Acids blend (EPA/DHA 3000mg) – Natura Health Products Beyond Essential Fats  Probiotics 25-900 bil cfu (Ther-Biotic Complete, VSL#3)  Vitamin D (based on blood levels)  Medical Food (Xymogen I5)
  • 27. REMOVE  DFH GI MicrobX or Prothera Undecylex  Parasites: BioPure Artemesinin or Mimosa Pudica  Bacterial: Syntrion SyGest + SanPharma Firmus  Fungal: Syntrion SyRegule + SanPharma Candida- Roqueforti suppositories  Fungal Sinus: Syntrion SyFungin & Argentyn 23 NS  PEKANA Mucan, Helmin, Opsonot, Mundipur  Natural Immunogenics Argentyn 23 liquid/spray  Detoxification: PEKANA Basic Detoxification & Drainage Kit (apo-Hepat, Renelix, Itires)  Syntrion SyDetox for “hot liver” signs & symptoms
  • 28. TREATING H. PYLORI WITHOUT ANTIBIOTICS  OrthoMolecular Products Pyloricil (Zinc carnosine, Mastic gum, Berberine, Bismuth citrate) x 2 mos  Lactoferrin  Probiotics/Kefir  Always check H. pylori stool Ag 1 month after completion of therapy
  • 29. PARASITE THERAPY  B. hominis: SMX/TMP + Metronidazole/Secnidazole  Cryptosporidia: Nitazoxanide (Alinia)  Dientamoeba fragiis: Iodoquinol  Enterobius Vermicularis (PW): Pyrantel Pamoate  Giardia: Tinidazole/Metronidazole  Entamoeba histolytica: Iodoquinol  Worms: Albendazole/Mebendazole  Apothecure pharmacy – Paragone 5 and Paragone 6 (compounded combination of antiparasitics)
  • 30. REPLACE  Theramedix DGX  Betaine HCL  Standard Process Cholachol  Natural Factors PGX (konjac root)
  • 31. REPAIR  GI Cocktail: 1 heaping tsp of glutamine powder in ½ cup of George’s Aloe Vera juice 2-3 x day  ECGC (green tea)  Curcumin  Xymogen IgG 2000/Xymogen I5
  • 32. REINOCULATE  Klaire Labs Ther-Biotic Complete (25 bil CFU)  VSL#3 (caps 112.5 bil CFU, packets 450 bil CFU, and DS packets (requires Rx) 900 bil CFU  Saccharomyces boulardii (C. difficile)  Thorne Research Arabinex
  • 33. REBALANCE  Address emotional toxins - ERT, counseling, journaling, Inner Child meditation, compassionate forgiveness  Balance autonomic nervous system - acupuncture, meditation, breath work, yoga, Tai Chi, Ballroom Dancing, PEMF, Microcurrent therapy (CES), Low- level laser
  • 34. SPECIALIST REFERRAL LIST  Biological/Holistic Dentist  Chiropractor  Acupuncturist  Massage Therapist  Craniosacral Therapist  Eden Energy Practitioner  Holistic Psychological Counselors
  • 35. FINAL ADVICE  Stay open to possibilities  See the world through the eyes of a child  Embrace change  Take with you what resonates with you and leave the rest alone (what feels right)  Never stop evolving (transformation/growth)
  • 36. MINDFULNESS “Mindfulness practice means that we commit fully in each moment to be present; inviting ourselves to interface with this moment in full awareness, with the intention to embody as best we can an orientation of calmness, mindfulness, and equanimity right here and right now.” Jon Kabat-Zinn, Wherever You Go, There You Are
  • 37. ALCAT TEST Cell Science Systems 852 South Military Trail Deerfield Beach, Florida 33442 www.alcat.com

Editor's Notes

  1. In the healthy GI tract, with intact mucous membranes, tolerance is the predominant immunological function. If the GI tract barrier is compromised, there is a breakdown in tolerance, leading to increased reactivity, chronic activation of immune system cells, and production of Ag-Ab complexes and cytokines that can have localized and systemic effects.
  2. Tight junctions between GI epithelial cells are regulated by proteins including Zonulins, Occludins, Claudins, as well as Kinases (enzymes)
  3. Middle East Journal of Family Medicine April 2009