REVIEW article
Front. Aging Neurosci.
Sec. Neurocognitive Aging and Behavior
Volume 17 - 2025 | doi: 10.3389/fnagi.2025.1642240
Cross-generational Mechanisms of Maternal Gut Microbiota in Modulating Offspring Autism Spectrum Disorder Risk: From the Gut-Brain Axis to Translational Challenges in Precision Interventions
Provisionally accepted
- West China Second University Hospital, Sichuan University, Chengdu, China
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Autism Spectrum Disorder (ASD) manifests as a group of neurodevelopmental disorders with high clinical and genetic heterogeneity, characterized by core features including social communication deficits, repetitive behaviors, and restricted interests. Current research primarily focuses on genetic variations, immune dysregulation, synaptic dysfunction, and gene-environment interactions. Nowadays, accumulating evidence indicates that maternal gut microbiota dysbiosis, induced by high-fat diets, antibiotic overuse, and urbanization, significantly correlates with abnormal fetal neurodevelopment and increased ASD risk. This review systematically delineates three transplacental mechanisms whereby maternal dysbiosis regulates fetal neurodevelopment: Metabolite-mediated pathways, Immune pathway activation, and Epigenetic reprogramming. Meanwhile, the key translational challenges are highlighted. At last, metagenomics-metabolomics-fetal neuroimaging, Development of microbiota metabolite-treated brain organoids, and Artificial Intelligence-driven (AI-driven) probiotic screening were proposed as research directions in future.
Keywords: maternal gut microbiota, Autism Spectrum Disorder, gut-brain axis, Microbial Metabolites, Perinatal dysbiosis, Fetal neurodevelopment
Received: 18 Jun 2025; Accepted: 29 Sep 2025.
Copyright: © 2025 Zhang, Zhou, Qiu, Xu, Liu, Liu and Xie. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Liang Xie, xeronxie@163.com
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