June 26, 2019
Investigators from the University of Central Florida (UCF) College of Medicine in Orlando found that high levels of propionic acid (PPA) — used in processed foods to extend shelf life — alters neuronal development in the fetal brain.
The study links maternal PPA exposure to "disturbed neural patterning during early stages of embryonic neural development leading to overproliferation of glial cells, abnormal neural architecture, and increased inflammatory profile; possible precursors for autism," the researchers, led by Saleh Naser, PhD, note.
"This is an intriguing finding and a first in the field," they add, cautioning that much more research is required to elucidate these early observations.
The study was published online June 19 in Scientific Reports.
"There are good reasons to suggest the gut-brain axis is a potential culprit in ASD pathogenesis," the researchers point out.
Naser told Medscape Medical News she was interested in understanding why children with ASD often develop gastrointestinal disease and was "intrigued" by published reports that associated dysbiosis and higher levels of PPA in stool samples from children with the disorder.
"I wanted to know more about the role of the microbiome and GI disorders, if any, with brain development," she said.
In laboratory experiments, the UCF team found that exposing human fetal neural stem cells to excessive PPA levels disrupted the natural balance between brain cells by reducing the number of cells that differentiate into neurons and by boosting the number that become glial cells.
Although glial cells help develop and protect neuron function, an overabundance of glial cells (gliosis) can disturb connectivity between neurons and cause inflammation, which has been observed in the brains of children with ASD.
Excessive PPA levels also disrupt the molecular pathways that normally allow neurons to communicate with the rest of the body, the researchers found.
"The combination of reduced neurons and damaged pathways impede the brain's ability to communicate, resulting in behaviors that are often found in children with autism, including repetitive behavior, mobility issues and inability to interact with others," the investigators state in a news release.
Previous studies have proposed links between autism and environmental and genetic factors, but the investigators note that the current study is the first to show a molecular link between elevated levels of PPA, the proliferation of glial cells, disturbed neural circuitry, and autism.
Naser said she hopes this study will further the "discussion that dysbiosis may lead to domination of microorganisms that are capable of producing metabolites which could interfere with brain development during early pregnancy."
Moving forward, the researchers hope to replicate the findings in mice and to study whether a high-PPA maternal diet leads to offspring with ASD-like behavior.
The research was funded by UCF. The authors have disclosed no relevant financial relationships.
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SOURCE: Medscape, June 26, 2019. Sci Rep. Published online June 19, 2019.