With the emerging evidence, the consensus about the multifactorial nature of Autism Spectrum Disorders (ASD) is building. The scientific literature provides numerous evidence for environmental factors accounting for the apparently higher prevalence of this condition. Current research has shown that gut microbiota play a critical role in emotional and cognitive development. The brain-gut-microbiota axis is the communication network between the brain, the gut, and the bacteria residing there. Both development and maintenance of a diverse gut flora is important for healthy neurological activity, behavior, mood and cognition. Studies emphasize the possible correlation between Clostridium sp., gut colonization, and possible development or exacerbating of ASD in affected children.
Association of gut dysbiosis and autism
Gastrointestinal disorders are one of the most common comorbidities reported in patients with ASD. Significant percentage of children with autism have a history of extensive antibiotic use. The oral antibiotics significantly disrupt protective intestinal microbiota, creating a favorable environment for colonization by opportunistic pathogens. A significant association has been demonstrated between antibiotic therapy and resultant alterations in the gut microbiome (gut dysbiosis)-which predispose C. difficile overgrowth in gut in early infancy. Clostridia can impact dopamine, epinephrine, and norepinephrine levels and contribute to various behavioral symptoms of autism.
Clostridium infection induced Behavioral Alteration
Various studies have reported high concentrations of Clostridia metabolites in the urine of children with autism. The severity of the autism was directly related to a higher concentration of dopamine metabolite Homovanillic acid (HVA) in the urine as well. Homovanillic acid (HVA) is formed from dopamine that escapes conversion to norepinephrine.
Dopamine is converted into norepinephrine by an enzyme called dopamine beta-hydroxylase. Children who had clostridia infection had lower levels of beta-hydroxylase enzyme resulting in an excess level of dopamine with low levels of norepinephrine. This makes the dopamine try to compensate for the lack of norepinephrine. This compensation can cause “obsessive, compulsive, stereotypical behavior's” associated with brain dopamine excess as well as reduced exploratory behavior and learning that are associated with brain norepinephrine deficiency.
Systemic effects of Inhibition of Norepinephrine and Epinephrine by Clostridium
Not only does Clostridia metabolites alter brain neurotransmitters, the inhibition of the production of norepinephrine and epinephrine by them may have a prominent effect on the production of neurotransmitters by the sympathetic nervous system and the adrenal gland as well.
Release of dopamine by the adrenal glands
Norepinephrine is the major neurotransmitter of the sympathetic nervous system that regulates the eyes, sweat glands, blood vessels, heart, lungs, stomach, and intestine. An inadequate supply of norepinephrine or a substitution of dopamine for norepinephrine might result in various systemic effects. The adrenal gland might also begin to release dopamine instead. It actually produces norepinephrine and epinephrine.
Free radical damage
In addition to abnormal physiology caused by dopamine substitution for norepinephrine, dopamine excess causes free radical damage to the tissues producing it. This can lead to permanent damage of the brain, adrenal glands, and sympathetic nervous system if the Clostridia metabolites persist for prolonged periods of time, if glutathione is severely depleted, and if there is apoptotic damage caused by other dopamine metabolites.
Gastrointestinal Clostridia bacteria have the ability to markedly alter behavior in autism by production of phenolic compounds that dramatically alter the balance of both dopamine and norepinephrine. Excess dopamine causes abnormal behavior, depletes the brain of glutathione and NADPH, causes a vicious cycle producing large quantities of oxygen superoxide that causes severe brain damage. These alterations appear to be a major factor in the causation of autism.
Treating chronic infections is a key strategy in helping children with Autism/ADHD/ASD at Functional Medicine clinic.
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References
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Shaw, W. (2010). Increased urinary excretion of a 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), an abnormal phenylalanine metabolite ofClostridiaspp. in the gastrointestinal tract, in urine samples from patients with autism and schizophrenia. Nutritional Neuroscience, 13(3), 135–143. https://doi.org/10.1179/147683010x12611460763968
Tucker, I. (2022, January 19). Inhibition of dopamine conversion to norepinephrine by Clostridia metabolites appears to be a (the) major cause of autism, schizophrenia, and other neuropsychiatric disorders. Great Plains Laboratory. https://www.greatplainslaboratory.com/articles-1/2018/7/23/inhibition-of-dopamine-conversion-to-norepinephrine-by-clostridia-metabolites-appears-to-be-a-the-major-cause-of-autism-schizophrenia-and-other-neuropsychiatric-disorders
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