GI Biology, Pathology, GI Biology, Pathology, and Treatment Strategiesand Treatment Strategies

Autism One ConferenceAutism One ConferenceCanadaCanada

October 2009October 2009

Sonja Hintz, R.N.Sonja Hintz, R.N.Anju Usman, M.D.Anju Usman, M.D.

True Health Medical CenterTrue Health Medical CenterNaperville, IllinoisNaperville, Illinois

What Defeat Autism Now What Defeat Autism Now Doctors know about GI issues…Doctors know about GI issues…

• Autism is a neuro-immune inflammatory Autism is a neuro-immune inflammatory condition affecting the gut and braincondition affecting the gut and brain

• Much of the inflammation originates in the gutMuch of the inflammation originates in the gut

• Many of the symptoms we call autistic, are Many of the symptoms we call autistic, are related to the gutrelated to the gut

• Treating the gut, is one of the most Treating the gut, is one of the most successful biomedical interventionssuccessful biomedical interventions

• Healing the Gut is the Key to successHealing the Gut is the Key to success

What does the gut do for us?What does the gut do for us?• Protection/BarrierProtection/Barrier

• Immune ProtectionImmune Protection

• Provides Fuel/NutritionProvides Fuel/Nutrition

• Transportation/MotilityTransportation/Motility

• Digestion (stomach, duodenum, jejunum)Digestion (stomach, duodenum, jejunum)– FatsFats– CarbohydratesCarbohydrates– ProteinProtein

• Absorption (ileum)Absorption (ileum)

• Waste Removal (colon)Waste Removal (colon)

The GI tract is our The GI tract is our first line of first line of defense against defense against the outside world.the outside world.

• Absorptive surface of Absorptive surface of the GI tract is 200 the GI tract is 200 times larger than the times larger than the surface area of the surface area of the skin (400 square skin (400 square meters)meters)

GI HistologyGI Histology

100 trillion bacteria in 100 trillion bacteria in the gut the gut

Early disruption of gut Early disruption of gut flora, affects later flora, affects later immune function, immune function, potential allergies and potential allergies and autoimmunityautoimmunity

Good flora protects us Good flora protects us from pathogensfrom pathogens

Aids with digestion of Aids with digestion of carbohydrates and fiber carbohydrates and fiber to form SCFA which in to form SCFA which in turn fuels enterocytesturn fuels enterocytes

Gut Gut MicrobiotaMicrobiota

Human Microbiome Project Human Microbiome Project • 5yr/ $140 million effort to study and explore how the trillions of 5yr/ $140 million effort to study and explore how the trillions of

microscopic organisms in our bodies affect our health. microscopic organisms in our bodies affect our health.

• Total microbial cells found in association with humans may Total microbial cells found in association with humans may exceed the total number of cells making up the human body exceed the total number of cells making up the human body by a factor of 10:1. by a factor of 10:1.

• The total number of genes associated The total number of genes associated

with the human microbiome could with the human microbiome could

exceed the total number of human genesexceed the total number of human genes

by a factor of 100:1by a factor of 100:1

• Organisms expected to be found, bacteriaOrganisms expected to be found, bacteria

yeast, protazoa, parasites viruses, yeast, protazoa, parasites viruses,

bacteriophagesbacteriophages

The Immune System in the GutThe Immune System in the Gut

GALT (gut-associated lymphoid tissue) with organized GALT (gut-associated lymphoid tissue) with organized lymphoid structures — Peyer's patches and isolated lymphoid structures — Peyer's patches and isolated lymphoid follicleslymphoid follicles

The diffuse tissues of the lamina propria contain a large The diffuse tissues of the lamina propria contain a large number of immunoglobulin A (IgA)number of immunoglobulin A (IgA)++ plasma cells, T and plasma cells, T and B cells, macrophages, dendritic cells (DCs) and stromal B cells, macrophages, dendritic cells (DCs) and stromal cells (SCs)cells (SCs)

The Gut/Brain/Immune ConnectionThe Gut/Brain/Immune Connection

The Vagus nerve The Vagus nerve inherently communicates with the inherently communicates with the splenic nerve to suppress TNF alpha production by splenic nerve to suppress TNF alpha production by macrophages in the spleen and modulate immune macrophages in the spleen and modulate immune function. (Dr. Rosas-Ballina)function. (Dr. Rosas-Ballina)

• Parasympathetic Parasympathetic

• Efferent or MotorEfferent or Motor

• Afferent or Sensory (80%)Afferent or Sensory (80%)• Back to the brain from the ear,Back to the brain from the ear,

tongue, larynx, GItongue, larynx, GI

• Dorsal Vagal NucleusDorsal Vagal Nucleus• Motor Motor to to Pharynx, Larynx, GI..Pharynx, Larynx, GI..

• Releases ACh (acetylcholine) Releases ACh (acetylcholine) • Nicotinic ReceptorsNicotinic Receptors• Muscarinic ReceptorsMuscarinic Receptors

J Clin Invest. 2007 Feb;117(2):289-96.J Clin Invest. 2007 Feb;117(2):289-96.

Tracey KJ..

• The nervous system, via an inflammatory reflex The nervous system, via an inflammatory reflex of the vagus nerve, can inhibit cytokine release of the vagus nerve, can inhibit cytokine release and thereby prevent tissue injury and death. and thereby prevent tissue injury and death.

• The efferent neural signaling pathway is termed The efferent neural signaling pathway is termed the cholinergic antiinflammatory pathway. the cholinergic antiinflammatory pathway.

• Cholinergic agonists inhibit cytokine synthesis Cholinergic agonists inhibit cytokine synthesis and protect against cytokine-mediated diseases.and protect against cytokine-mediated diseases.

• Stimulation of the vagus nerve prevents the Stimulation of the vagus nerve prevents the damaging effects of cytokinedamaging effects of cytokine

Physiology and immunology of the Physiology and immunology of the cholinergic anti-inflammatory pathwaycholinergic anti-inflammatory pathway

Gastrointestinal Dysfunction (literature)Gastrointestinal Dysfunction (literature)• MaldigestionMaldigestion

– Decreased activity of digestive enzymes Decreased activity of digestive enzymes (Horvath,1999. Buie, 2004)(Horvath,1999. Buie, 2004)– High levels of opioid peptides found in urine of autistics. High levels of opioid peptides found in urine of autistics. (Reichelt, 1997)(Reichelt, 1997)

• MalabsorptionMalabsorption

• Dysbiosis Dysbiosis – Dysbiosis or altered bowel flora Dysbiosis or altered bowel flora (Rossenau, 2004)(Rossenau, 2004)– Clostridial overgrowth Clostridial overgrowth (Sandler, 2002)(Sandler, 2002)– Persistent measles virus Persistent measles virus (Wakefield, Krigsman)(Wakefield, Krigsman)

• Immune Dysregulation Immune Dysregulation (allergy, autoimmunity, inflammation, deficiency)(allergy, autoimmunity, inflammation, deficiency)– Autistic Enterocolitis, Lymphoid Hyperplasia Autistic Enterocolitis, Lymphoid Hyperplasia (Wakefield, Krigsman, Balzola)(Wakefield, Krigsman, Balzola)– Increased intestinal permeability leading to food sensitivitiesIncreased intestinal permeability leading to food sensitivities and autoimmunity and autoimmunity (Vodjani, 2002)(Vodjani, 2002)– Increased pro-inflammatory cytokines – LP, TNF alpha, IFN gamma Increased pro-inflammatory cytokines – LP, TNF alpha, IFN gamma (Ashwood, 2004)(Ashwood, 2004)– Proinflammatory response to dietary proteins Proinflammatory response to dietary proteins (Jyonuchi, 2004)(Jyonuchi, 2004)– Low Secretory IgA Low Secretory IgA (Gupta, 1996)(Gupta, 1996)

• MotilityMotility– Gastroesophageal Reflux associated with aggressive behaviorGastroesophageal Reflux associated with aggressive behavior(Buie)(Buie)

Gastrointestinal Dysfunction (experience)Gastrointestinal Dysfunction (experience)• MaldigestionMaldigestion

– IgG Food SensitivitiesIgG Food Sensitivities (dairy, gluten, soy…) (dairy, gluten, soy…)– Poor weight gainPoor weight gain– Low Essential Amino AcidsLow Essential Amino Acids– Low Stomach Acid/BloatingLow Stomach Acid/Bloating

• Malabsorption Malabsorption – Fat Soluble Vitamin Deficiencies Fat Soluble Vitamin Deficiencies – Essential Fatty Acid DeficienciesEssential Fatty Acid Deficiencies– Low weight and heightLow weight and height– Dry-Bumpy Skin, Ear Wax Excess, Floating StoolsDry-Bumpy Skin, Ear Wax Excess, Floating Stools

• Dysbiosis Dysbiosis (fungal, bacterial, viral) (fungal, bacterial, viral) – Chronic Strep IssuesChronic Strep Issues– Chronic Anaerobic Overgrowth (clostridia sp.)Chronic Anaerobic Overgrowth (clostridia sp.)– Chronic Small Bowel Bacterial Overgrowth (SBBO)Chronic Small Bowel Bacterial Overgrowth (SBBO)– Chronic Yeast/Fungal OvergrowthChronic Yeast/Fungal Overgrowth

• Immune Dysregulation/InflammationImmune Dysregulation/Inflammation– Behaviors, Stims, Sleep disorder, Posturing, Aggression, Self InjuriousBehaviors, Stims, Sleep disorder, Posturing, Aggression, Self Injurious

• MotiMotilitylity– Chronic Constipation, Reflux, Burping, HypotoniaChronic Constipation, Reflux, Burping, Hypotonia

Measles Virus, Colitis, and ASDMeasles Virus, Colitis, and ASD• Mol Pathol. 2002 Apr;55(2):84-90.Mol Pathol. 2002 Apr;55(2):84-90.

Potential viral pathogenic mechanism for new variant Potential viral pathogenic mechanism for new variant inflammatory bowel disease.inflammatory bowel disease.

Uhlmann V, , Martin CM, , Sheils O, , Pilkington L, , Silva I, , Killalea A, , Murch SB, , Walker-Smith J, , Thomson M, , Wakefield AJ, , O'Leary JJ..

A new form of inflammatory bowel disease (ileocolonic lymphonodular hyperplasia) A new form of inflammatory bowel disease (ileocolonic lymphonodular hyperplasia) has been described in a cohort of children with developmental disorder. This study has been described in a cohort of children with developmental disorder. This study investigates the presence of persistent measles virus in the intestinal tissue of investigates the presence of persistent measles virus in the intestinal tissue of these patients (new variant inflammatory bowel disease) and a series of controls by these patients (new variant inflammatory bowel disease) and a series of controls by molecular analysis. molecular analysis.

RESULTS: Seventy five of 91 patients with a histologically confirmed diagnosis of ileal RESULTS: Seventy five of 91 patients with a histologically confirmed diagnosis of ileal lymphonodular hyperplasia and enterocolitis were positive for measles virus in their lymphonodular hyperplasia and enterocolitis were positive for measles virus in their intestinal tissue compared with five of 70 control patients. Measles virus was intestinal tissue compared with five of 70 control patients. Measles virus was identified within the follicular dendritic cells and some lymphocytes in foci of identified within the follicular dendritic cells and some lymphocytes in foci of reactive follicular hyperplasia. The copy number of measles virus ranged from one reactive follicular hyperplasia. The copy number of measles virus ranged from one to 300,00 copies/ng total RNA.to 300,00 copies/ng total RNA.

CONCLUSIONSCONCLUSIONS: : The data confirm an association between the The data confirm an association between the presence of measles virus and gut pathology in children with presence of measles virus and gut pathology in children with developmental disorder.developmental disorder.

PMID: 11950955PMID: 11950955

Seventy five of 91 patients with a histologically Seventy five of 91 patients with a histologically confirmed diagnosis of ileal lymphonodular confirmed diagnosis of ileal lymphonodular hyperplasia and enterocolitis were positive for measles hyperplasia and enterocolitis were positive for measles virus in their intestinal tissue compared with five of 70 virus in their intestinal tissue compared with five of 70 control patients. Measles virus was identified within control patients. Measles virus was identified within the follicular dendritic cells and some lymphocytes in the follicular dendritic cells and some lymphocytes in foci of reactive follicular hyperplasia.foci of reactive follicular hyperplasia.

Bacterial Co-infections and ASDBacterial Co-infections and ASD• J Neurosci Res. 2007 Apr;85(5):1143-8.J Neurosci Res. 2007 Apr;85(5):1143-8.

Evidence for Mycoplasma ssp., Chlamydia pneunomiae, and human Evidence for Mycoplasma ssp., Chlamydia pneunomiae, and human herpes virus-6 coinfections in the blood of patients with autistic herpes virus-6 coinfections in the blood of patients with autistic spectrum disorders.spectrum disorders.

Nicolson GL, , Gan R, , Nicolson NL , , Haier J..

– We examined the blood of 48 patients from central and southern We examined the blood of 48 patients from central and southern California diagnosed with autistic spectrum disorders (ASD) by using California diagnosed with autistic spectrum disorders (ASD) by using forensic polymerase chain reaction and found that forensic polymerase chain reaction and found that a large subset a large subset (28/48 or 58.3%) of patients showed evidence of Mycoplasma spp. (28/48 or 58.3%) of patients showed evidence of Mycoplasma spp. infections compared with two of 45 (4.7%) age-matched control infections compared with two of 45 (4.7%) age-matched control

– We found that Mycoplasma-positive and -negative ASD patients had similar We found that Mycoplasma-positive and -negative ASD patients had similar percentages of C. pneumoniae and HHV-6 infections,percentages of C. pneumoniae and HHV-6 infections, suggesting that such suggesting that such infections occur independently in ASD patients. Control subjects also had low infections occur independently in ASD patients. Control subjects also had low rates of C. pneumoniae (1/48 or 2.1%) and HHV-6 (4/48 or 8.3%) infections, rates of C. pneumoniae (1/48 or 2.1%) and HHV-6 (4/48 or 8.3%) infections, and there were no coinfections in control subjects. and there were no coinfections in control subjects.

– The results indicate that a large subset of ASD patients shows The results indicate that a large subset of ASD patients shows evidence of bacterial and/or viral infections (odds ratio = 16.5, P < evidence of bacterial and/or viral infections (odds ratio = 16.5, P < 0.001). The significance of these infections in ASD is discussed in 0.001). The significance of these infections in ASD is discussed in terms of appropriate treatment. (c) 2007 Wiley-Liss, Inc. terms of appropriate treatment. (c) 2007 Wiley-Liss, Inc. PMID:17265454 PMID:17265454

Propionic Acid, Dysbiosis and ASDPropionic Acid, Dysbiosis and ASD• Behav Brain Res. 2007 Jan 10;176(1):149-69. Epub 2006 Sep 1.Behav Brain Res. 2007 Jan 10;176(1):149-69. Epub 2006 Sep 1.

Neurobiological effects of intraventricular propionic acid in rats: Neurobiological effects of intraventricular propionic acid in rats: possible role of short chain fatty acids on the pathogenesis and possible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders.characteristics of autism spectrum disorders.

MacFabe DF

– PPA is a by-product of a subpopulation of human gut enterobacteria and is a short chain fatty acid and an important intermediate of cellular metabolism. Also a common food preservative.

– PPA produced reversible repetitive dystonic behaviours, hyperactivity, turning behaviour, retropulsion, caudate spiking, and the progressive development of limbic kindled seizures, suggesting that this compound has central effects.

– Biochemical analyses of brain homogenates from PPA treated rats Biochemical analyses of brain homogenates from PPA treated rats showed an increase in oxidative stress markers (e.g., lipid peroxidation showed an increase in oxidative stress markers (e.g., lipid peroxidation and protein carbonylation) and glutathione S-transferase activity and protein carbonylation) and glutathione S-transferase activity coupled with a decrease in glutathione and glutathione peroxidase.coupled with a decrease in glutathione and glutathione peroxidase.

– PPA treated rats revealed increased reactive astrogliosis (GFAP immunoreactivity) and activated microglia (CD68 immunoreactivity) suggestive of a neuroinflammatory process.

PMID: 16950524

Clostridia and ASDClostridia and ASD• Clin Infect Dis. 2002 Sep 1;35(Suppl 1):S6-S16.Clin Infect Dis. 2002 Sep 1;35(Suppl 1):S6-S16.

Gastrointestinal microflora studies in late-onset Gastrointestinal microflora studies in late-onset autism.autism.

Finegold SM

– Some cases of late-onset (regressive) autism may involve abnormal Some cases of late-onset (regressive) autism may involve abnormal flora because oral vancomycin, which is poorly absorbed, may lead to flora because oral vancomycin, which is poorly absorbed, may lead to significant improvement in these children.significant improvement in these children.

– The number of clostridial species found in the stools of children with The number of clostridial species found in the stools of children with autism was greater than in the stools of control children. autism was greater than in the stools of control children.

– The most striking finding was total absence of non-spore-forming The most striking finding was total absence of non-spore-forming anaerobes and microaerophilic bacteria from control children and anaerobes and microaerophilic bacteria from control children and significant numbers of such bacteria from children with autism.significant numbers of such bacteria from children with autism.

– These studies demonstrate significant alterations in the upper and These studies demonstrate significant alterations in the upper and lower intestinal flora of children with late-onset autism and may provide lower intestinal flora of children with late-onset autism and may provide insights into the nature of this disorder.insights into the nature of this disorder.

Clostridia and ASDClostridia and ASD• J Child Neurol. 2000 Jul;15(7):429-35. J Child Neurol. 2000 Jul;15(7):429-35. LinksLinks

Short-term benefit from oral vancomycin treatment of Short-term benefit from oral vancomycin treatment of regressive-onset autismregressive-onset autism

Sandler RH, , Finegold SM, , Bolte ERBolte ER, , Buchanan CPBuchanan CP, , Maxwell APMaxwell AP, , Väisänen MLVäisänen ML, , Nelson MNNelson MN, , Wexler HMWexler HM..

– We speculated that, in a subgroup of children, disruption of indigenous We speculated that, in a subgroup of children, disruption of indigenous gut flora might promote colonization by one or more neurotoxin-producing gut flora might promote colonization by one or more neurotoxin-producing bacteria, contributing, at least in part, to their autistic symptomatologybacteria, contributing, at least in part, to their autistic symptomatology . .

– Entry criteria included antecedent broad-spectrum antimicrobial exposure Entry criteria included antecedent broad-spectrum antimicrobial exposure followed by chronic persistent diarrhea, deterioration of previously followed by chronic persistent diarrhea, deterioration of previously acquired skills, and then autistic features. acquired skills, and then autistic features.

– Short-term improvement was noted using multiple pre- and post-therapy Short-term improvement was noted using multiple pre- and post-therapy evaluations. These included coded, paired videotapes scored by a clinical evaluations. These included coded, paired videotapes scored by a clinical psychologist blinded to treatment status; these noted improvement in 8 of psychologist blinded to treatment status; these noted improvement in 8 of 10 children studied. Unfortunately, these gains had largely waned at 10 children studied. Unfortunately, these gains had largely waned at follow-up. follow-up.

– These results indicate that a possible gut flora-brain connection warrants These results indicate that a possible gut flora-brain connection warrants further investigation, as it might lead to greater pathophysiologic insight further investigation, as it might lead to greater pathophysiologic insight and meaningful prevention or treatment in a subset of children with and meaningful prevention or treatment in a subset of children with autism.autism.

PMID: 10921511PMID: 10921511

PANDAS PANDAS Pediatric Autoimmune Neuropsychiatric Disorder Associated Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcuswith Streptococcus

• Presence of obsessive-compulsive disorder and/or a Presence of obsessive-compulsive disorder and/or a tic disorder tic disorder

• Pediatric onset of symptoms Pediatric onset of symptoms

• Episodic course of symptom severity Episodic course of symptom severity

• Association with group A Beta-hemolytic Association with group A Beta-hemolytic streptococcal infection (a positive throat culture for streptococcal infection (a positive throat culture for Strep or history of Scarlet Fever) Strep or history of Scarlet Fever)

• Association with neurological abnormalities (motoric Association with neurological abnormalities (motoric hyperactivity, or adventitious movements, such as hyperactivity, or adventitious movements, such as choreiform movements)choreiform movements)

• Diagnoses based on symptoms and High ASO and Diagnoses based on symptoms and High ASO and AntiDNAse ABAntiDNAse AB

Chronic Infectious Agents and Chronic Infectious Agents and Chronic Disease EffectsChronic Disease Effects

• These agents create These agents create inflammation, free radicals inflammation, free radicals and oxidative stress.and oxidative stress.

• Some of these biologic agents produce Some of these biologic agents produce neurotoxins neurotoxins and excitotoxins and excitotoxins and other toxic by-products.and other toxic by-products.

• Some agents increase cell membrane Some agents increase cell membrane permeabilitypermeability..• Our body may produce antibodies to these agents. Our body may produce antibodies to these agents.

These antibodies may cross react with our own These antibodies may cross react with our own tissue creating an autoimmune reaction. This is tissue creating an autoimmune reaction. This is called called molecular mimicrymolecular mimicry..

• Chronic infections Chronic infections disrupt neurotransmittersdisrupt neurotransmitters

SAM

SAH

MTase

SAHH

Homocysteine

B6

THF

CBS

B12BHMT

Choline

Betaine

Impact of Oxidative Stress on Methionine Metabolism

Transsulfuration Pathway

THF: tetrahydrofolateCystathionine

Cysteine

Glutathione

Methionine

AK

ADA

Inosine

AMP

B6

Methylation of DNA, RNA, Proteins, Catecholamines, Phospholipids, Creatine

Enzymes

MS

MAT

5-CH3THF Adenosine

GSSG

Basic Biomedical StrategyBasic Biomedical Strategy• History and Physical ExaminationHistory and Physical Examination• Laboratory TestingLaboratory Testing• Clean UpClean Up

– Environmental ControlsEnvironmental Controls– Dietary InterventionsDietary Interventions– Address Gastrointestinal HealthAddress Gastrointestinal Health

• Foundational NutrientsFoundational Nutrients• Treat Underlying Immune Issues and Treat Underlying Immune Issues and

InflammationInflammation• Support Detoxification Pathways, esp. Support Detoxification Pathways, esp.

Methylation and SulfationMethylation and Sulfation• Address Mitochondrial DysfunctionAddress Mitochondrial Dysfunction• Heavy Metal DetoxificationHeavy Metal Detoxification

History - GastrointestinalHistory - Gastrointestinal• History of Colic, RefluxHistory of Colic, Reflux• Frequent AntibioticsFrequent Antibiotics• Dairy Intolerance, Sugar CravingsDairy Intolerance, Sugar Cravings• Frequent Otitis Media or SinusitisFrequent Otitis Media or Sinusitis• History of Thrush, Severe Diaper RashHistory of Thrush, Severe Diaper Rash• Poorly Formed Stools, Odd Color, Consistency, Poorly Formed Stools, Odd Color, Consistency,

Odor, Mucus, “Soft Serve”Odor, Mucus, “Soft Serve”• Undigested Food in Stools, Floating StoolsUndigested Food in Stools, Floating Stools• Constipation, Chronic Diarrhea, BothConstipation, Chronic Diarrhea, Both• Abdominal Distention, GassinessAbdominal Distention, Gassiness• Abnormal PosturingAbnormal Posturing• Self Injurious Behavior, Aggression Self Injurious Behavior, Aggression • Poor Sleeping HabitsPoor Sleeping Habits

PhysicalPhysical• Poor growth – height, weight, head circumferencePoor growth – height, weight, head circumference• Pale skin, spider veins, long eye lashesPale skin, spider veins, long eye lashes• Skin- rash, sand paper skin, eczema, warts, acne Skin- rash, sand paper skin, eczema, warts, acne molluscum contagiosum, red anal ringmolluscum contagiosum, red anal ring• Dilated pupils, lack of eye contact, divergent gaze,Dilated pupils, lack of eye contact, divergent gaze, poor visual tracking, squinting poor visual tracking, squinting • Allergic shiners, Nasal crease, Mouth breathing Allergic shiners, Nasal crease, Mouth breathing • Nails – spots, ridges, fungusNails – spots, ridges, fungus• Coated tongue or thrush, mouth ulcers, cracked lipsCoated tongue or thrush, mouth ulcers, cracked lips• Enlarged tonsilsEnlarged tonsils• LymphadenopathyLymphadenopathy• Spleen tendernessSpleen tenderness• Abdominal bloatingAbdominal bloating• Hypotonia, W-sitting, Flabby muscles, StrabismusHypotonia, W-sitting, Flabby muscles, Strabismus• Ligamentous laxity (double jointed)Ligamentous laxity (double jointed)• Signs of precocious puberty- facial hair, pubic hair Signs of precocious puberty- facial hair, pubic hair

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Clean up the Child’s DietClean up the Child’s Diet• Casein-free/Gluten-freeCasein-free/Gluten-free/Soy-free Diet Trial for 3-6 months./Soy-free Diet Trial for 3-6 months.• Avoid sugar and refined starch, high fiber diet, maximize Avoid sugar and refined starch, high fiber diet, maximize

antioxidants, cruciferous veggies, turmeric, garlic…antioxidants, cruciferous veggies, turmeric, garlic…• Limit processed and preserved foodsLimit processed and preserved foods; ; organic is best.organic is best.• Avoid Avoid excitotoxinsexcitotoxins (ex. Caffeine, MSG, NutraSweet, red/yellow food dyes, (ex. Caffeine, MSG, NutraSweet, red/yellow food dyes,

nitrites, sulfites, glutamates, preservatives).nitrites, sulfites, glutamates, preservatives).

• Limit intake of Limit intake of phenolicsphenolics (apples, grapes, strawberries).(apples, grapes, strawberries).

• Limit sources of Limit sources of CopperCopper (chocolate, shellfish, tap water, artificial food dyes).(chocolate, shellfish, tap water, artificial food dyes).

• Drink plenty of clean filtered water.Drink plenty of clean filtered water.• Eliminate seafood.Eliminate seafood.• Begin meals with raw fruits and veggies.Begin meals with raw fruits and veggies.• Add good fats Add good fats (cold pressed, hexane-free) – oils, nuts, seeds.(cold pressed, hexane-free) – oils, nuts, seeds.• Avoid hydrogenated, trans-fats, fried or heated fats.Avoid hydrogenated, trans-fats, fried or heated fats.• Buy hormone-free, antibiotic-free, organic, GMO-free Buy hormone-free, antibiotic-free, organic, GMO-free especially especially

animal products such as eggs, meat and dairy.animal products such as eggs, meat and dairy.• Add fermented foods (coconut kefir, cabbage, kombucha).Add fermented foods (coconut kefir, cabbage, kombucha).

CF/GF DietCF/GF Diet

Persistent Gut IssuesPersistent Gut Issues Hyperactivity/StimmingHyperactivity/Stimming

SpecificSpecificCarbohydrateCarbohydrate

DietDiet

Body Ecology Body Ecology DietDiet

Low Oxalate Low Oxalate Diet Diet

Avoid ExcitotoxinsAvoid Excitotoxins

Low Phenolic/FeingoldLow Phenolic/FeingoldDiet Diet

Low Copper DietLow Copper Diet

Elimination/RotationElimination/RotationDietDiet

Elimination/RotationElimination/RotationDietDiet

Dietary DetoursDietary Detours

Opioid PeptidesOpioid Peptides• Casein/gluten peptides are broken down by the enzyme Casein/gluten peptides are broken down by the enzyme

DPPIV(dipeptidyl dipeptidase 4). This enzyme can be DPPIV(dipeptidyl dipeptidase 4). This enzyme can be disabled by toxic metals and yeast.disabled by toxic metals and yeast.

• These peptides act as false neurotransmitters, creating These peptides act as false neurotransmitters, creating problems with behavior, focus, attention, mood regulation, problems with behavior, focus, attention, mood regulation, and processing info. Other symptoms include high pain and processing info. Other symptoms include high pain tolerance, dilated pupils, addiction to dairy and gluten tolerance, dilated pupils, addiction to dairy and gluten products. products.

• High levels of opioid peptides (gliadorphin and High levels of opioid peptides (gliadorphin and caseomorphine) found in urine of autistics. (Reichelt, 1997)caseomorphine) found in urine of autistics. (Reichelt, 1997)

• Casein-free, Gluten-free diet may be an effective Casein-free, Gluten-free diet may be an effective intervention (Whiteley,1999)intervention (Whiteley,1999)

Specific Carbohydrate DietSpecific Carbohydrate DietElaine Gottschall BA, M.Sc.Elaine Gottschall BA, M.Sc.

• The allowed carbohydrates are monosaccharides and have a single The allowed carbohydrates are monosaccharides and have a single molecule structure that allow them to be easily absorbed by the molecule structure that allow them to be easily absorbed by the intestine wall.intestine wall.

• Complex carbohydrates which are disaccharides (double molecules) Complex carbohydrates which are disaccharides (double molecules) and polysaccharides (chain molecules) are not allowed. and polysaccharides (chain molecules) are not allowed.

• Complex carbohydrates that are not easily digested feed harmful Complex carbohydrates that are not easily digested feed harmful bacteria in our intestines causing them to overgrow producing by bacteria in our intestines causing them to overgrow producing by products and inflaming the intestine wall. products and inflaming the intestine wall.

• ““The diet works by starving out these bacteria and restoring the The diet works by starving out these bacteria and restoring the balance of bacteria in our gut.”balance of bacteria in our gut.”

www.breakingtheviciouscycle.info/beginners www.breakingtheviciouscycle.info/beginners www.pecanbread.comwww.pecanbread.com

Celiac Disease Presenting as AutismCeliac Disease Presenting as AutismStephen J. Genuis, MD, and Thomas P. Bouchard, BScStephen J. Genuis, MD, and Thomas P. Bouchard, BSc

Gluten-restricted diets have become increasingly popular among parents seeking Gluten-restricted diets have become increasingly popular among parents seeking treatment for children diagnosed with autism. Some of the reported response to celiac treatment for children diagnosed with autism. Some of the reported response to celiac diets in children with autism may be related to amelioration of nutritional deficiency diets in children with autism may be related to amelioration of nutritional deficiency resulting from undiagnosed gluten sensitivity and consequent malabsorption. A case resulting from undiagnosed gluten sensitivity and consequent malabsorption. A case is presented of a 5-year old boy diagnosed with severe autism at a specialty clinic for is presented of a 5-year old boy diagnosed with severe autism at a specialty clinic for autistic spectrum disorders. autistic spectrum disorders. After initial investigation suggested underlying celiac After initial investigation suggested underlying celiac disease and varied nutrient deficiencies, a gluten-free diet was instituted along with disease and varied nutrient deficiencies, a gluten-free diet was instituted along with dietary and supplemental measures to secure nutritional sufficiency. The patient’s dietary and supplemental measures to secure nutritional sufficiency. The patient’s gastrointestinal symptoms rapidly resolved, and signs and symptoms suggestive of gastrointestinal symptoms rapidly resolved, and signs and symptoms suggestive of autism progressively abated. autism progressively abated. This case is an example of a common malabsorption This case is an example of a common malabsorption syndrome associated with central nervous system dysfunction and suggests that in syndrome associated with central nervous system dysfunction and suggests that in some contexts, nutritional deficiency may be a determinant of developmental delay. It some contexts, nutritional deficiency may be a determinant of developmental delay. It is recommended that all children with neurodevelopmental problems be assessed for is recommended that all children with neurodevelopmental problems be assessed for nutritional deficiency and malabsorption syndromes.nutritional deficiency and malabsorption syndromes.

Child Neurol OnlineFirst, published on June 29, 2009Child Neurol OnlineFirst, published on June 29, 2009

Low Oxalate Diet (LOD)Low Oxalate Diet (LOD)Susan Owen BSSusan Owen BS

• Oxalates are abundant in many plant foods Oxalates are abundant in many plant foods

• When the gut is inflamed or becomes permeable excess When the gut is inflamed or becomes permeable excess oxalate from foods can be absorbedoxalate from foods can be absorbed

• When present in high amounts can lead to oxidative When present in high amounts can lead to oxidative damage, depletion of glutathione, and inflammationdamage, depletion of glutathione, and inflammation

• Excess oxalates form crystals after binding with calciumExcess oxalates form crystals after binding with calcium• Symptoms include: Pain, Burning, Frequent Urination, Symptoms include: Pain, Burning, Frequent Urination,

Eye Poking, Family history of Kidney Stones, VulvodyniaEye Poking, Family history of Kidney Stones, Vulvodynia• Avoid High Oxalate Foods Avoid High Oxalate Foods

– Spinach, Greens, Nuts, Soy, BeetsSpinach, Greens, Nuts, Soy, Beets• Avoid Calcium and High Doses of Vitamin CAvoid Calcium and High Doses of Vitamin C

Food additives and hyperactive behavior in 3-year-Food additives and hyperactive behavior in 3-year-old and 8/9-year-old children in the community: a old and 8/9-year-old children in the community: a randomized, double-blinded, placebo-controlled trialrandomized, double-blinded, placebo-controlled trial

• The Lancet 2007The Lancet 2007• examined the effect of artificial coloring and preservatives on examined the effect of artificial coloring and preservatives on

hyperactive behavior in children. After consuming an additive-free hyperactive behavior in children. After consuming an additive-free diet for six weeks, the children were given either a placebo beverage diet for six weeks, the children were given either a placebo beverage

or one containing a mix of additives in two-week intervals.or one containing a mix of additives in two-week intervals. In the In the additive group, hyperactive behaviors increased.additive group, hyperactive behaviors increased.

• the study caused many pediatricians to rethink their skepticism about the study caused many pediatricians to rethink their skepticism about

a link between diet and A.D.H.Da link between diet and A.D.H.D. . “The overall findings of the “The overall findings of the study are clear and require that even we skeptics, who study are clear and require that even we skeptics, who have long doubted parental claims of the effects of have long doubted parental claims of the effects of various foods on the behavior of their children, admit we various foods on the behavior of their children, admit we might have been wrong,” might have been wrong,” reported a February issue of AAP reported a February issue of AAP Grand Rounds, a publication of the American Academy of Pediatrics.Grand Rounds, a publication of the American Academy of Pediatrics.

Excitotoxins - GlutamateExcitotoxins - Glutamate• GlutamatesGlutamates

– Monosodium Monosodium Glutamate (MSG)Glutamate (MSG)

– Hydrolyzed ProteinHydrolyzed Protein– Modified Food StarchModified Food Starch– Natural FlavorsNatural Flavors– Peas, Mushrooms, Peas, Mushrooms,

TomatoesTomatoes– Parmesan CheeseParmesan Cheese– ProteinProtein

• Anti- GlutamatesAnti- Glutamates– PycnogenolPycnogenol– Rosemary, Lemon BalmRosemary, Lemon Balm– Skull Cap, ChamomileSkull Cap, Chamomile– MagnesiumMagnesium– TaurineTaurine– GABAGABA– L- TheanineL- Theanine– Vitamin KVitamin K– LithiumLithium– Namenda (drug)Namenda (drug)– Minocycline (antibiotic)Minocycline (antibiotic)Excitotoxins Excitotoxins = Substances that cause an excess of = Substances that cause an excess of

excitatory neurotransmission in the brain. If inhibitory excitatory neurotransmission in the brain. If inhibitory neurotransmission is lacking, the excess excitation may neurotransmission is lacking, the excess excitation may lead to neuronal death. Neuronal death leads to chronic lead to neuronal death. Neuronal death leads to chronic inflammation in the brain.inflammation in the brain.

Lab Options for Gut IssuesLab Options for Gut Issues• Urine Organic Acids Test (OATS, MAP)Urine Organic Acids Test (OATS, MAP)• Stool MicrobiologyStool Microbiology• Stool MycologyStool Mycology• Stool ParasitologyStool Parasitology• IgG/IgE Food/Mold Antibody PanelIgG/IgE Food/Mold Antibody Panel• Celiac Panel, Carnitine level, Vit D25 OH, retinolCeliac Panel, Carnitine level, Vit D25 OH, retinol• Fecal FatFecal Fat• Breath Test for Fructose MalabsorptionBreath Test for Fructose Malabsorption• Inflammatory Markers Inflammatory Markers (ESR, CRP, histamine, calprotectin,(ESR, CRP, histamine, calprotectin,

…)…)

• Ammonia - blood,urineAmmonia - blood,urine• IBD Serology (prometheus testing)IBD Serology (prometheus testing)• Endoscopy, Colonoscopy if necessaryEndoscopy, Colonoscopy if necessary

General Treatment StrategiesGeneral Treatment Strategies• Address Maldigestion - Address Maldigestion -

– Add Digestive EnzymesAdd Digestive Enzymes

• Address MalabsorptionAddress Malabsorption– Add Probiotics, Essential FatsAdd Probiotics, Essential Fats– Address Fat Soluble Vitamin DeficienciesAddress Fat Soluble Vitamin Deficiencies– Add LipaseAdd Lipase

• Address DysbiosisAddress Dysbiosis• Diagnose and Treat Immune DysregulationDiagnose and Treat Immune Dysregulation

– Address Food Hypersensitivities Address Food Hypersensitivities – Treat ImmunodeficienciesTreat Immunodeficiencies– Treat Chronic InflammationTreat Chronic Inflammation

• Address Motility/ConstipationAddress Motility/Constipation

Clean up the Child’s GutClean up the Child’s Gut• Daily bowel movements are a goal.Daily bowel movements are a goal.• Add digestive Add digestive enzymesenzymes with meals. with meals.• Start high potency Start high potency probioticsprobiotics..• Start treatment for Start treatment for dysbiosis.dysbiosis.• Address Address constipation.constipation.• Check for high Check for high ammoniaammonia, treat accordingly, treat accordingly• If persistent symptoms:If persistent symptoms:

– Eliminate disaccharides from diet for 3-6 months Eliminate disaccharides from diet for 3-6 months • Specific Carbohydrate DietSpecific Carbohydrate Diet

– Consider referral to knowledgeable GI specialistConsider referral to knowledgeable GI specialist– Consider trial of IV or nasal SecretinConsider trial of IV or nasal Secretin– Add anti-inflammatory agents.Add anti-inflammatory agents.

Keep close eye on gut during any detox regimen.Keep close eye on gut during any detox regimen.Acute regression most likely due to gut issues.Acute regression most likely due to gut issues.

Constipation has got to go!Constipation has got to go!• Magnesium citrateMagnesium citrate

• Buffered Vitamin CBuffered Vitamin C

• Increased fiber/fluidsIncreased fiber/fluids

• Avoid opiate peptidesAvoid opiate peptides

• Massage, ReboundingMassage, Rebounding

• SennaSenna

• Polyethylene glycol Polyethylene glycol

• Suppositories or Suppositories or Enemas if neededEnemas if needed

• Cholinergic AgentsCholinergic Agents– UrecholineUrecholine– Phosphatidyl CholinePhosphatidyl Choline

• May mask as May mask as diarrheadiarrhea

• Check a KUB xrayCheck a KUB xray

• If it takes greater If it takes greater than 24 hrs to pass than 24 hrs to pass charcoal or beets, charcoal or beets, consider motility consider motility issuesissues

Treating Dysbiosis/Co-infectionsTreating Dysbiosis/Co-infections

• ClostridiaClostridia

• YeastYeast

• Bacteria and StrepBacteria and Strep

• ParasitesParasites

• VirusesViruses

ClostridiaClostridiaproduce produce toxinstoxinsand enzymes and enzymes that create that create severe gutsevere gutinflammation inflammation and produceand producewatery watery diarrheadiarrhea

Clostridia IssuesClostridia IssuesSymptoms

– Aggressive– OCD– Temper– Agitation– Irritable– Very foul stools– Mucus in stools– Severe diarrhea following

antibiotic use

Treatment – Probiotics, High Potency

single strain– Sacchyromyces Boulardii– Antibiotics

• Vancomycin• Metronidazole (Flagyl)

– Herbals– Immune modulators– Homeopathics– HBOT– Carnitine

Yeast IssuesYeast IssuesSymptoms

– Spacey– Foggy thinking– Inappropriate

laughter– Sugar cravings– Poor sleep– Frequent diaper rash– Frequent urination– History of frequent

antibiotics

Treatment Options– Limit carbs, sugar, yeast– Probiotics– Sacchromyces Boulardii– Zinc, Molybdenum– Antifungals

• Drugs – Nystatin, Ampho B– Fluconazole– Itraconazole– Ketoconazole

• Herbals– Berberine– Grapefruit Seed Extract– Oil of Oregano, Pau d’Arco– Garlic, Samento, …

– Enzymes– Homeopathics

Strep Issues Strep Issues Symptoms

– Ritualistic– Repetitive– Verbal tics– Obsessive– Compulsive– Verbal stims– Frequent strep

infections– Frequent bacterial

infections

Treatment Options– Probiotics– Alkalinization– Xylitol– Antibacterial Herbs

• Goldenseal• Neem• Berberine

– Immune modulators• Oral Immunoglobulins• Transfer Factors• Colostrum• Mushroom Extracts• Beta Glycans• Plant Sterols

– Drugs• Penicillin• Zithromax

– Homeopathics

ParasitesParasitesSymptoms

– Bizarre Behavior– Insatiable Appetite– Aggressive– Worse at full moon– Picking, biting, licking,

itching, grinding– Fecal smearing– Restlessness

Treatment – Probiotics– Antiparasitic Drugs

• Flagyl• Paromomycin• Mebendazole• Alinia

– Natural Remedies• Wormwood(artemesia)• Black Walnut• Pumpkin Seeds• Clove• Coconut Oil

– Homeopathics• Combo remedies

Viral IssuesViral IssuesSymptoms

– Easy Fatigue– Visual Issues

• Squinting• Divergent Gaze• Poor Eye Contact

– Cold sores– Warts– History of Regression

after MMR or other live viruses

Treatment Options– Antiviral Agents

• Olive Leaf Extract, Elderberry• Caprylic Acid• High Dose Vitamin A

– Antiviral Drugs• Acyclovir• Valacyclovir• Famvir• Imunovir

– Immune Support• Low Dose Naltrexone• Red. Glutathione• Zinc• Immune Modulators

Anti-inflammatory AgentsAnti-inflammatory Agents• Herbs Herbs

– Boswellia, Green Tea, Nettles, Slippery Elm, Cat’s Claw, Boswellia, Green Tea, Nettles, Slippery Elm, Cat’s Claw, DGLicorice, Aloe, Ginger, Garlic, Echinacea, Ginseng, …DGLicorice, Aloe, Ginger, Garlic, Echinacea, Ginseng, …

• Bioflavinoids (carotenoids, catechins)Bioflavinoids (carotenoids, catechins)– Curcumin, Hesperidin, Pycnogenol, Quercetin and Rutin.Curcumin, Hesperidin, Pycnogenol, Quercetin and Rutin.

• Antioxidant rich fruits and veggies, and nutrientsAntioxidant rich fruits and veggies, and nutrients– GlutathioneGlutathione

• Omega 3 and Omega 6(DGLA) EFAsOmega 3 and Omega 6(DGLA) EFAs

• Sulfates help to seal a leaky gut- Epsom Salts Baths, …Sulfates help to seal a leaky gut- Epsom Salts Baths, …

• Cholinergic agonistsCholinergic agonists– Phosphatidyl Choline, Phosphatidyl Serine, Galantamine, Nicotinic Phosphatidyl Choline, Phosphatidyl Serine, Galantamine, Nicotinic

AcidAcid• MedsMeds

– SingulairSingulair, , Actos, Celebrex… Actos, Celebrex…

Aggarwal, B.B. and K.B. Harikumar, Aggarwal, B.B. and K.B. Harikumar, Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases.autoimmune and neoplastic diseases. Int J Biochem Cell Biol, 2009. Int J Biochem Cell Biol, 2009. 4141(1): p. 40-59.(1): p. 40-59.

Additional Sources of InformationAdditional Sources of Information

• Autism: Effective Biomedical TreatmentsAutism: Effective Biomedical Treatments, Pangborn and , Pangborn and BakerBaker

• Healing the New Childhood EpidemicsHealing the New Childhood Epidemics, Ken Bock, MD, Ken Bock, MD• Children with Starving BrainsChildren with Starving Brains, Jaquelyn McCandless MD, Jaquelyn McCandless MD• Special Diets for Special KidsSpecial Diets for Special Kids, Lisa Lewis, Lisa Lewis• Changing the Course of AutismChanging the Course of Autism, B. Jepson MD and Jane , B. Jepson MD and Jane

JohnsonJohnson• Nourishing HopeNourishing Hope, Julie Matthews, Julie Matthews• Nourishing TraditionsNourishing Traditions, Sally Fallon, Sally Fallon

Thank You. Thank You.