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Expression of miRNAs in Pre-Schoolers with Autism Spectrum Disorders Compared with Typically Developing Peers and Its
Letizia Guiducci1, Manuela Cabiati1, Elisa Santocchi2
1CNR, Institute of Clinical Physiology, 56124 Pisa, Italy.
Abstract:
Alteration of the microbiota-gut-brain axis has been recently recognized as a possible contributor to the physiopathology of autism spectrum disorder (ASD). In this context, microRNA (miRNAs) dysfunction, implicated both in several neuropathological conditions including ASD and in different gastrointestinal disorders (GIDs), could represent an important modulating factor. In this contextual framework, we studied the transcriptional profile of specific circulating miRNAs associated with both ASD (miR-197-5p, miR-424-5p, miR-500a-5p, miR-664a-5p) and GID (miR-21-5p, miR-320a-5p, miR-31-5p, miR-223-5p) in a group of pre-schoolers with ASD and in typically developing (TD) peers. In the ASD group, we also assessed the same miRNAs after a 6-month supplementation with probiotics and their correlation with plasma levels of zonulin and lactoferrin. At baseline, the expression of miRNAs involved in ASD were significantly reduced in ASD pre-schoolers vs. TD controls. Regarding the miRNAs involved in GID, the expression levels of miR-320-5p, miR-31-5p, and miR-223-5p were significantly higher in ASD than in TD subjects, whereas miR-21-5p showed significantly reduced expression in the ASD group vs. TD group. Supplementation with probiotics did not significantly change the expression of miRNAs in the ASD population. We found a significative negative correlation between zonulin and miR-197-5p and miR-21-5p at baseline, as well as between lactoferrin and miR-223-5p after 6 months of probiotic supplementation. Our study confirms the presence of an altered profile of the miRNAs investigated in ASD versus TD peers that was not modified by supplementation with probiotics.
Insights
Altered microRNA (miRNA) profiles are linked to autism spectrum disorder (ASD) and gastrointestinal disorders (GIDs) in preschoolers. Probiotic supplementation did not alter these miRNA levels, but correlations with gut health markers were observed.
Area of Science:
- Neuroscience
- Genetics
- Gastroenterology
Background:
- The microbiota-gut-brain axis is increasingly recognized for its role in autism spectrum disorder (ASD) pathophysiology.
- MicroRNA (miRNA) dysfunction is implicated in both ASD and gastrointestinal disorders (GIDs), suggesting a potential modulating role.
Purpose of the Study:
- To investigate circulating miRNA profiles associated with ASD and GIDs in preschool children with ASD compared to typically developing peers.
- To assess the impact of probiotic supplementation on these miRNA levels and their correlation with gut health markers (zonulin, lactoferrin) in children with ASD.
Main Methods:
- Transcriptional profiling of specific circulating miRNAs (miR-197-5p, miR-424-5p, miR-500a-5p, miR-664a-5p for ASD; miR-21-5p, miR-320a-5p, miR-31-5p, miR-223-5p for GID) in preschool children.
- Comparison of miRNA expression between ASD and typically developing (TD) groups at baseline.
- Assessment of miRNA levels after a 6-month probiotic supplementation in the ASD group.
- Correlation analysis with plasma zonulin and lactoferrin levels.
Main Results:
- ASD preschoolers showed significantly reduced expression of ASD-associated miRNAs compared to TD controls.
- Expression levels of GID-associated miRNAs (miR-320a-5p, miR-31-5p, miR-223-5p) were significantly higher in ASD, while miR-21-5p was reduced.
- Probiotic supplementation did not significantly alter miRNA expression in the ASD group.
- Significant negative correlations were found between zonulin and miR-197-5p/miR-21-5p at baseline, and between lactoferrin and miR-223-5p post-supplementation.
Conclusions:
- The study confirms an altered circulating miRNA profile in preschool children with ASD compared to TD peers.
- Probiotic supplementation did not modify the investigated miRNA profiles in children with ASD.
- Observed correlations suggest a link between specific miRNAs and gut permeability/health markers in the context of ASD.
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01:19Autism Spectrum Disorder
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01:22MicroRNAs