Founder and director of The Great Plains Laboratory in Lenexa, Kansas.
Compound from Clostridia Bacteria Elevated in Autism and Schizophrenia; Elevated HPHPA Levels May Indicate a Microbial Overgrowth in the Intestinal Tract
A significant biochemical finding that may play a role in the etiology of autism has been discovered by William Shaw, PhD, director of The Great Plains Laboratory, Inc and recently reported in the peer-reviewed journal Nutritional Neuroscience. The compound identified as 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA) was found in significantly higher concentrations in urine samples of children with autism compared to age and sex appropriate controls.
The highest value measured in urine samples was 7500 mmol/mol creatinine, a value 300 times the median normal adult value, in a patient with acute schizophrenia during an acute psychotic episode. The psychosis ceased after treatment with oral vancomycin, an antibiotic that kills bacteria, with a simultaneous and significant decrease in HPHPA. The source of this compound appears to be multiple species of anaerobic bacteria of the Clostridium genus.
The significance of this compound is that it is a probable metabolite of the amino acid m-tyrosine (3-hydroxyphenylalanine), a tyrosine analog (a substance slightly chemically altered from the predominant biochemical substance) which depletes brain catecholamines and causes symptoms of autism (stereotypical behavior, hyperactivity, and hyper-reactivity) in experimental animals. In addition, the enkephalins, substances that regulate emotion and feelings, may also be dysregulated by this compound or other compounds in the same biochemical pathway. As a result, it is possible that abnormally elevated HPHPA, produced by abnormal microorganisms from phenylalanine in the gastrointestinal tract, may play a causal role in autism just as abnormally elevated phenylalanine and its metabolites cause the disorder phenylketonuria (PKU). The major difference being that elevated phenylalanine (the marker for PKU) results from a hereditary metabolic defect, while HPHPA results from one or more species of Clostridia bacteria.
Bolte reported that children with autism had a marked decrease in autistic symptoms when treated with antibiotics effective against Clostridia. Therefore, the treatment of abnormal microbial overgrowth may be a promising new therapy for individuals with autism with abnormal HPHPA elevations. Curiously, 50 years ago, elevated amounts of this compound in urine samples was observed and associated with general mental illness but this discovery was ignored until the work of Shaw rediscovered it. For over ten years, The Great Plains Laboratory, Inc. in Lenexa, Kansas has utilized gas-chromatography mass-spectrometry to evaluate biochemical abnormalities that appear to be of microbial origin in urine samples of children with autism and other developmental disorders and also in adults with a wide variety of disorders. In an earlier study involving two brothers with autism, it was discovered that certain microbial metabolites (breakdown products of the metabolism of microorganisms) were found to be abnormally high in their urine compared to normal individuals.
Shaw says that more than 500 species of microorganisms are found in the gastrointestinal tract and that we still know very little about the microorganisms in our own intestines. Numerous physicians have been using this marker as an important part of their treatment of autism and other illnesses with good clinical responses. Shaw believes that this work may be of comparable importance for autism as the discovery revealing the presence of intestinal Helicobacter pylori in ulcer patients, which was found to be a major contributing cause of stomach ulcers.
Click here to read more from the article Increased urinary excretion of a 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), an abnormal phenylalanine metabolite of Clostridia spp. in the gastrointestinal tract, in urine samples from patients with autism and schizophrenia by William Shaw, PhD.
William Shaw, PhD has spent the last ten years researching biochemical abnormalities that appear to be of microbial origin in urine samples of children with autism and other developmental disorders, as well as in adults with a wide variety of disorders.