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A new study has identified about a dozen saliva-based micro RNAs associated with gastrointestinal disorders in children with neurodevelopmental conditions, including autism. The researchers hope their findings could help one day lead to individualized treatments for such patients.

The lead author is David Q. Beversdorf, a clinician at the University of Missouri Thompson Center for Autism and Neurodevelopmental Disorders. The report appears in Frontiers in Psychiatry.

“We wanted to understand how a child’s body responds to the various bacteria living in the mouth and determine if these interactions contribute to gastrointestinal symptoms,” said Steve Hicks, an associate professor of pediatrics at the Penn State College of Medicine, and one of Beversdorf’s collaborators on the study. “By identifying these specific microRNAs in the saliva of children with autism, these molecules may serve as future targets for developing novel treatments or tracking medication effectiveness in children with autism-related gastrointestinal conditions.”

Many patients with autism spectrum disorder (ASD) or other neurodevelopmental disorders, also have gastrointestinal or digestive issues, including constipation and diarrhea. Further, they may not respond to typical treatments.

Earlier work has shown that the salivary micro-transcriptome (non-coding RNA and microbial RNA) can distinguish between children with autism spectrum disorder (ASD) and peers with typical development or non-ASD associated developmental delay. These non-coding RNAs have regulatory roles in metabolism, cell differentiation, and neuronal differentiation, by inhibiting gene expression.

In this study, saliva samples were collected from nearly 900 children, with ASD, non-ASD developmental delay (DD), or typical development (TD). Some of these children had autism and experienced gastrointestinal disturbances. The children came from several academic medical centers across the United States.

The saliva micro-transcriptome of each child was assessed with RNA-seq and they were aligned to microbial and human databases. A Kruskal Wallis analysis of variance (ANOVA) was used to compare levels of 1821 micro-transcriptome features across neurodevelopmental status (ASD, DD, or TD) and GI condition presence or absence. An ANOVA was also used to compare micro-transcriptome levels among GI sub-groups— constipation, reflux, food intolerance, other GI condition, no GI condition—and to identify RNAs that differed among children taking three common GI medications—probiotics, reflux medication, or laxatives.

After analyzing the samples, the researchers identified specific RNA biomarkers linked to children who had autism and experienced gastrointestinal symptoms.

Fifty-seven salivary RNAs differed between GI sub-groups. The microRNA differences between food intolerance and reflux groups were most common. Twelve microRNAs displayed an effect of GI disturbance and showed association with GI medication uses and measures of behavior. These dozen microRNAs displayed enrichment for 13 physiologic pathways, including metabolism/digestion long-term depression, and neurobiology of addiction.

Beversdorf noted that RNA have regulatory properties throughout the human body, and the specific RNA identified in the study may have regulatory effects on biological pathways related to metabolism, digestion, depression, and addiction.

“It’s one of those ‘chicken or the egg’ cases where we still don’t know if it is the RNA potentially contributing to the gastrointestinal issues, or if the gastrointestinal issues are causing the RNA to be expressed differently, but we have identified a relationship, which will be useful to further explore going forward,” he said.

He added that, “This research can potentially help contribute to precision medicine one day, where we can follow children with autism and gastrointestinal symptoms over an extended period of time and assess how they might respond to personalized treatments, with the ultimate goal of reducing their symptoms and improving their quality of life.”

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