REVIEW article
Front. Cell. Infect. Microbiol.
Sec. Intestinal Microbiome
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1601888
This article is part of the Research TopicNatural Compounds from Plant: Microbiome-targeted Therapeutic Strategy for Gastrointestinal DisordersView all 5 articles
Neurodevelopmental disorders and gut-brain interactions: exploring the therapeutic potential of pycnogenol through microbial-metabolic-neural networks
Provisionally accepted
- Department of Pediatrics, ShengJing Hospital of China Medical University, Shenyang, Liaoning Province, China
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Neurodevelopmental disorders (NDDs), characterized by cognitive impairments and behavioral abnormalities, represent a clinically diverse group of conditions typically emerging during childhood or adolescence. Major subtypes encompass autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and epilepsy. The pathogenesis of these disorders involves multifactorial interactions between genetic susceptibility (Shank3 mutations in ASD), environmental triggers (prenatal toxins), neurotransmitter dysregulation (dopamine (GA) and γ-aminobutyric acid (GABA) systems) and immune dysregulation. Growing research highlights the gut-brain axis disruption as a potential contributor to NDDs pathophysiology, though systematic evaluation of therapeutic approaches targeting this axis and related gastrointestinal comorbidities (GIDs) remains limited. This review comprehensively examines the pathological mechanisms underlying ADHD, ASD, and epilepsy, while analyzing the reciprocal relationship between gut-brain axis dysregulation and GID manifestations in NDDs. Notably, abnormal activation of key signaling pathways including NF-κB, MAPK and PI3K/AKT/mTOR is strongly associated with the pathogenesis of NDDs. We further propose pycnogenol (PYC), a polyphenol extract of pine bark, as a natural compound with multiple bioactivities such as anti-inflammatory and antioxidant, can directly or indirectly affect the function of the gut-brain axis by regulating the structure of the intestinal microbial community (increasing the abundance of Akkermansia muciniphila and butyric acid-producing bacteria) and its metabolites, providing a new strategy for the treatment of NDDs.
Keywords: Neurodevelopmental disorders, attention-deficit hyperactivity disorder, Autism Spectrum Disorder, Epilepsy, Pycnogenol, gut-brain axis
Received: 28 Mar 2025; Accepted: 19 May 2025.
Copyright: © 2025 Chen, Li and Fan. 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: Yuying Fan, Department of Pediatrics, ShengJing Hospital of China Medical University, Shenyang, Liaoning Province, China
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