Investigators at the University of Central Florida (UCF) have just identified the molecular changes that happen when neuronal stem cells are exposed to high levels of an acid commonly found in processed foods. The research team has taken a step closer to showing the link between the food pregnant women consume and the effects on a fetus’ developing brain. Findings from the new study—which described how high levels of propionic acid (PPA), used to increase the shelf life of packaged foods and inhibit mold in commercially processed cheese and bread, reduce the development of neurons in fetal brains—were published recently in Scientific Reports through an article titled “Propionic Acid Induces Gliosis and Neuro-inflammation through Modulation of PTEN/AKT Pathway in Autism Spectrum Disorder.”

The researchers began their work after reports showed that autistic children often suffer from gastric issues such as irritable bowel syndrome. They wondered about a possible link between the gut and the brain and began examining how the microbiome differed between people with autism and those who do not have the condition.

“Studies have shown a higher level of PPA in stool samples from children with autism and the gut microbiome in autistic children is different,” noted senior study investigator Saleh Naser, PhD, professor and associate director of graduate affairs. “I wanted to know what the underlying cause was.”

The research group found that exposing neural stem cells to excessive PPA damages brain cells in several ways. First, the acid disrupts the natural balance between brain cells by reducing the number of neurons and overproducing glial cells. While glial cells help develop and protect neuron function, too many glia cells disturb connectivity between neurons. They also cause inflammation, which has been noted in the brains of autistic children.

“We investigated the effect of propionic acid (PPA), a short-chain fatty acid (SCFA), and a product of dysbiotic ASD gut, on human neural stem cells (hNSCs) proliferation, differentiation, and inflammation. hNSCs proliferated to 66 neurospheres when exposed to PPA versus 45 in control,” the authors wrote. “The neurosphere diameter also increased at day 10 post-PPA treatment to (Mean: 193.47 um ± SEM: 6.673 um) versus (154.16 um ± 9.95 um) in control, p < 0.001. Pre-treatment with β-HB, SCFA receptor inhibitor, hindered neurosphere expansion (p < 0.001). While hNSCs spontaneously differentiated to (48.38% ± 6.08%) neurons (Tubulin-IIIβ positive) and (46.63% ± 2.5%) glia (GFAP positive), PPA treatment drastically shifted differentiation to 80% GFAP cells (p < 0.05).”

Excessive amounts of the acid shorten and damage pathways that neurons use to communicate with the rest of the body. 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.

Previous studies have proposed links between autism and environmental and genetic factors, Naser says their study is the first to discover the molecular link between elevated levels of PPA, the proliferation of glial cells, disturbed neural circuitry and autism.

PPA occurs naturally in the gut and a mother’s microbiome changes during pregnancy and can cause increases in the acid. But eating packaged foods containing the acid can further increase PPA in the woman’s gut, which then crosses to the fetus.

More research needs to be done before drawing clinical conclusions. Next, the research team will attempt to validate its findings in mice models by seeing if a high PPA maternal diet causes autism in mice genetically predisposed to the condition. There is no cure for autism, which affects about 1 in 59 children, but the scientists hope their findings will advance studies for ways to prevent the disorder.

“This research is only the first step towards a better understanding of autism spectrum disorder,” the UCF scientists concluded. “But we have confidence we are on the right track to finally uncovering autism etiology.”

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