Ochratoxin A and the Pathobiology of Autism
Aspergillus mycotoxin and its association with autism - Medical Academy of Pediatric Special Needs - part 8
A 2019 article published in Nutritional Neuroscience by B. DeSantis, et.al. describes the role of mycotoxins, particularly ochratoxin A (OTA), in the pathobiology of autism. Ochratoxin A, one of the most common toxins produced by Aspergillus mold can cause variety of health problems, including kidney disease and neurological damage. OTA is also considered immunotoxic and carcinogenic. This compound is commonly found on urine mycotoxin tests such as the MycoTOX Profile from Mosaic Diagnostics (image 1).
Image 1 - ochratoxin A elevations are common with aspergillus mold exposure through water-damaged buildings or contamination of foods, e.g., grains.
The following is a brief outline of findings discussed in the B. DeSantis:
OTA interacts with neurodevelopment and synapse function. Disruption in these systems can lead to neurological and psychiatric conditions involving autism.
OTA can disrupt liver detoxifying enzymes which can compromise digestive function leading to leaky gut.
Leaky gut and gastrointestinal inflammation have a strong interplay with food sensitivities and gut pathogens.
Lactobacillus and Bifidobacterium can help in counteracting certain mycotoxin exposures. Lactobacillus seems to specifically detoxify OTA.
OTA competes with phenylalanine which is involved in dopamine production. Dopamine is needed for attention and focus.
This last statement about OTA and phenylalanine is important. Dopamine deficiency can affect attention and focusing abilities. Other problems that can occur with lack of dopamine production is poor catecholamine production of norepinephrine and epinephrine. This can lead to poor brain function, attention and memory problems, and adverse cardiovascular function and fatigue. Severe deficiencies can lead to orthostatic problems in cardiovascular regulation.
Another article published in 2016 in Toxins shows the mechanism of Ochratoxin A (OTA) inhibition of phenylalanine to tyrosine conversion.
It turns out that OTA is an inhibitor of phenylalanine hydroxlase (see image 2 below) by behaving as a “false substrate” for the enzymes attempted hydroxylation (addition of a hydroxyl group, -OH) of phenylalanine to tyrosine.
Phenylalanine is converted to tyrosine through the action of phenylalanine hydroxylase. This enzyme reguires tetrahydrobiopterin (BH4) as a cofactor in its function. Severe blockage of phenylalanine hydroxylase can lead to phenylketonuria (or a PKU-like disorder) which is a devastating neurological disorder in children leading to brain damage, lowered IQ, and seizures.
Other mycotoxins associated with aspergillus exposure include aflatoxin M1 and gliotoxin which have their own toxicity effects. These chemicals are also detected through the MycoTOX Profile from Mosaic Diagnostics Laboratory.
For more information about the MycoTOX Profile visit the Mosaic Diagnostics Laboratory website. The test is available for purchase through Lab Tests Plus.