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100 trillion bacteria in the gut Early disruption of gut flora, affects later immune function, potential allergies and autoimmunity Good flora protects us from pathogens Aids with digestion of carbohydrates and fiber to form SCFA which in turn fuels enterocytes Gut Microbiota
5yr/ $140 million effort to study and explore how the trillions of microscopic organisms in our bodies affect our health.
Total microbial cells found in association with humans may exceed the total number of cells making up the human body by a factor of 10:1.
The total number of genes associated
with the human microbiome could
exceed the total number of human genes
by a factor of 100:1
Organisms expected to be found, bacteria
yeast, protazoa, parasites viruses,
The Immune System in the Gut GALT (gut-associated lymphoid tissue) with organized lymphoid structures — Peyer's patches and isolated lymphoid follicles The diffuse tissues of the lamina propria contain a large number of immunoglobulin A (IgA) + plasma cells, T and B cells, macrophages, dendritic cells (DCs) and stromal cells (SCs)
Potential viral pathogenic mechanism for new variant 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) 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 these patients (new variant inflammatory bowel disease) and a series of controls by molecular analysis.
RESULTS: Seventy five of 91 patients with a histologically confirmed diagnosis of ileal lymphonodular hyperplasia and enterocolitis were positive for measles virus in their intestinal tissue compared with five of 70 control patients. Measles virus was identified within the follicular dendritic cells and some lymphocytes in foci of reactive follicular hyperplasia. The copy number of measles virus ranged from one to 300,00 copies/ng total RNA.
CONCLUSIONS : The data confirm an association between the presence of measles virus and gut pathology in children with developmental disorder.
Seventy five of 91 patients with a histologically confirmed diagnosis of ileal lymphonodular hyperplasia and enterocolitis were positive for measles virus in their intestinal tissue compared with five of 70 control patients. Measles virus was identified within the follicular dendritic cells and some lymphocytes in foci of reactive follicular hyperplasia.
Evidence for Mycoplasma ssp., Chlamydia pneunomiae, and human herpes virus-6 coinfections in the blood of patients with autistic spectrum disorders.
Nicolson GL , Gan R , Nicolson NL , Haier J .
We examined the blood of 48 patients from central and southern California diagnosed with autistic spectrum disorders (ASD) by using forensic polymerase chain reaction and found that a large subset (28/48 or 58.3%) of patients showed evidence of Mycoplasma spp. infections compared with two of 45 (4.7%) age-matched control
We found that Mycoplasma-positive and -negative ASD patients had similar percentages of C. pneumoniae and HHV-6 infections, suggesting that such 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, and there were no coinfections in control subjects.
The results indicate that a large subset of ASD patients shows evidence of bacterial and/or viral infections (odds ratio = 16.5, P < 0.001). The significance of these infections in ASD is discussed in terms of appropriate treatment. (c) 2007 Wiley-Liss, Inc. PMID:17265454
Behav Brain Res. 2007 Jan 10;176(1):149-69. Epub 2006 Sep 1.
Neurobiological effects of intraventricular propionic acid in rats: possible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders.
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 showed an increase in oxidative stress markers (e.g., lipid peroxidation and protein carbonylation) and glutathione S-transferase activity 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.
Short-term benefit from oral vancomycin treatment of regressive-onset autism
Sandler RH , Finegold SM , Bolte ER , Buchanan CP , Maxwell AP , Väisänen ML , Nelson MN , Wexler HM .
We speculated that, in a subgroup of children, disruption of indigenous gut flora might promote colonization by one or more neurotoxin-producing bacteria, contributing, at least in part, to their autistic symptomatology .
Entry criteria included antecedent broad-spectrum antimicrobial exposure followed by chronic persistent diarrhea, deterioration of previously acquired skills, and then autistic features.
Short-term improvement was noted using multiple pre- and post-therapy evaluations. These included coded, paired videotapes scored by a clinical psychologist blinded to treatment status; these noted improvement in 8 of 10 children studied. Unfortunately, these gains had largely waned at follow-up.
These results indicate that a possible gut flora-brain connection warrants further investigation, as it might lead to greater pathophysiologic insight and meaningful prevention or treatment in a subset of children with autism.
PANDAS Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus
Presence of obsessive-compulsive disorder and/or a tic disorder
Pediatric onset of symptoms
Episodic course of symptom severity
Association with group A Beta-hemolytic streptococcal infection (a positive throat culture for Strep or history of Scarlet Fever)
Association with neurological abnormalities (motoric hyperactivity, or adventitious movements, such as choreiform movements)
Diagnoses based on symptoms and High ASO and AntiDNAse AB
Chronic Infectious Agents and Chronic Disease Effects
These agents create inflammation, free radicals and oxidative stress.
Some of these biologic agents produce neurotoxins and excitotoxins and other toxic by-products.
Some agents increase cell membrane permeability .
Our body may produce antibodies to these agents. These antibodies may cross react with our own tissue creating an autoimmune reaction. This is called molecular mimicry .
Chronic infections disrupt neurotransmitters
SAM SAH MTase SAHH Homocysteine B6 THF CBS B12 BHMT Choline Betaine Impact of Oxidative Stress on Methionine Metabolism Transsulfuration Pathway THF: tetrahydrofolate Cystathionine Cysteine Glutathione Methionine AK ADA Inosine AMP B6 Methylation of DNA, RNA, Proteins, Catecholamines, Phospholipids, Creatine Enzymes MS MAT 5-CH 3 THF Adenosine GSSG
Casein/gluten peptides are broken down by the enzyme DPPIV(dipeptidyl dipeptidase 4). This enzyme can be disabled by toxic metals and yeast.
These peptides act as false neurotransmitters, creating problems with behavior, focus, attention, mood regulation, and processing info. Other symptoms include high pain tolerance, dilated pupils, addiction to dairy and gluten products.
High levels of opioid peptides (gliadorphin and caseomorphine) found in urine of autistics. (Reichelt, 1997)
Casein-free, Gluten-free diet may be an effective intervention (Whiteley,1999)
Specific Carbohydrate Diet Elaine Gottschall BA, M.Sc.
The allowed carbohydrates are monosaccharides and have a single molecule structure that allow them to be easily absorbed by the intestine wall.
Complex carbohydrates which are disaccharides (double molecules) and polysaccharides (chain molecules) are not allowed.
Complex carbohydrates that are not easily digested feed harmful bacteria in our intestines causing them to overgrow producing by products and inflaming the intestine wall.
“ The diet works by starving out these bacteria and restoring the balance of bacteria in our gut.”
Stephen J. Genuis, MD, and Thomas P. Bouchard, BSc
Gluten-restricted diets have become increasingly popular among parents seeking 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 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 autistic spectrum disorders. After initial investigation suggested underlying celiac disease and varied nutrient deficiencies, a gluten-free diet was instituted along with dietary and supplemental measures to secure nutritional sufficiency. The patient’s gastrointestinal symptoms rapidly resolved, and signs and symptoms suggestive of autism progressively abated. This case is an example of a common malabsorption syndrome associated with central nervous system dysfunction and suggests that in some contexts, nutritional deficiency may be a determinant of developmental delay. It is recommended that all children with neurodevelopmental problems be assessed for nutritional deficiency and malabsorption syndromes.
Child Neurol OnlineFirst, published on June 29, 2009
When the gut is inflamed or becomes permeable excess oxalate from foods can be absorbed
When present in high amounts can lead to oxidative damage, depletion of glutathione, and inflammation
Excess oxalates form crystals after binding with calcium
Symptoms include: Pain, Burning, Frequent Urination, Eye Poking, Family history of Kidney Stones, Vulvodynia
Avoid High Oxalate Foods
Spinach, Greens, Nuts, Soy, Beets
Avoid Calcium and High Doses of Vitamin C
Food additives and hyperactive behavior in 3-year-old and 8/9-year-old children in the community: a randomized, double-blinded, placebo-controlled trial
The Lancet 2007
examined the effect of artificial coloring and preservatives on hyperactive behavior in children. After consuming an additive-free diet for six weeks, the children were given either a placebo beverage or one containing a mix of additives in two-week intervals. In the additive group, hyperactive behaviors increased.
the study caused many pediatricians to rethink their skepticism about a link between diet and A.D.H.D . “The overall findings of the study are clear and require that even we skeptics, who have long doubted parental claims of the effects of various foods on the behavior of their children, admit we might have been wrong,” reported a February issue of AAP Grand Rounds, a publication of the American Academy of Pediatrics.
Excitotoxins = Substances that cause an excess of excitatory neurotransmission in the brain. If inhibitory neurotransmission is lacking, the excess excitation may lead to neuronal death. Neuronal death leads to chronic inflammation in the brain.
Aggarwal, B.B. and K.B. Harikumar, Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol, 2009. 41 (1): p. 40-59.