Autism Spectrum Disorder (ASD) is a multifactorial neurodevelopmental condition characterized by impairments in social communication and behavior, frequently associated with gastrointestinal dysfunctions. Increasing evidence highlights the central role of the gut-brain axis (GBA), where alterations in biological barrier integrity, both at the intestinal epithelial barrier (IEB) and the blood-brain barrier (BBB) level, may contribute to systemic inflammation and neurodevelopmental alterations. In particular, increased intestinal permeability (“leaky gut”) has been reported in ASD and linked to microbial dysbiosis and immune dysregulation with potential downstream effects on BBB integrity through the systemic dissemination of pro-inflammatory mediators. The IEB plays a key role in maintaining homeostasis by regulating the selective passage of luminal components into systemic circulation. On this basis, we explored intestinal permeability in three environmental ASD murine models: Maternal Immune Activation (MIA), Post-natal Immune Activation (PIA) and Early Immune Activation (EIA), including both sexes to evaluate potential sex-related differences in barrier dysfunction. Expression of key tight junction (TJ) components (claudin-1, claudin-3, occludin and zonula occludens-1), was analyzed by RT-qPCR, revealing significant molecular alterations across all models. To further investigate gut-brain interactions, advanced microfluidic in vitro platforms are being established using IVTech bioreactors to recreate dynamic physiological conditions. The IEB will be modeled using a co-culture system, while the BBB will be mimicked using three-culture models providing a multicellular representation of neurovascular unit. In the IEB model, barrier integrity was assessed using Lucifer Yellow transwell permeability assays, showing a passage rate below 5% that confirmed the establishment of functional tight barrier cellular model. These models will help us to dissect mechanistic links between gut and brain interfaces and to identify key biomarkers of barriers dysfunction in ASD.
Breaking barriers: exploring gut-brain axis dysfunction in autism with advanced in vitro models
Ilenia Boccadoro;Giusi Sabatini;Roberta Prete;Aldo Corsetti;Natalia Battista
2026-01-01
Abstract
Autism Spectrum Disorder (ASD) is a multifactorial neurodevelopmental condition characterized by impairments in social communication and behavior, frequently associated with gastrointestinal dysfunctions. Increasing evidence highlights the central role of the gut-brain axis (GBA), where alterations in biological barrier integrity, both at the intestinal epithelial barrier (IEB) and the blood-brain barrier (BBB) level, may contribute to systemic inflammation and neurodevelopmental alterations. In particular, increased intestinal permeability (“leaky gut”) has been reported in ASD and linked to microbial dysbiosis and immune dysregulation with potential downstream effects on BBB integrity through the systemic dissemination of pro-inflammatory mediators. The IEB plays a key role in maintaining homeostasis by regulating the selective passage of luminal components into systemic circulation. On this basis, we explored intestinal permeability in three environmental ASD murine models: Maternal Immune Activation (MIA), Post-natal Immune Activation (PIA) and Early Immune Activation (EIA), including both sexes to evaluate potential sex-related differences in barrier dysfunction. Expression of key tight junction (TJ) components (claudin-1, claudin-3, occludin and zonula occludens-1), was analyzed by RT-qPCR, revealing significant molecular alterations across all models. To further investigate gut-brain interactions, advanced microfluidic in vitro platforms are being established using IVTech bioreactors to recreate dynamic physiological conditions. The IEB will be modeled using a co-culture system, while the BBB will be mimicked using three-culture models providing a multicellular representation of neurovascular unit. In the IEB model, barrier integrity was assessed using Lucifer Yellow transwell permeability assays, showing a passage rate below 5% that confirmed the establishment of functional tight barrier cellular model. These models will help us to dissect mechanistic links between gut and brain interfaces and to identify key biomarkers of barriers dysfunction in ASD.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
