Neurodevelopmental disorders and gut-brain interactions: exploring the therapeutic potential of pycnogenol through microbial-metabolic-neural networks.

This review looks at how the gut and brain are connected in conditions like autism, ADHD, and epilepsy. Researchers suggest that problems with gut bacteria and inflammation might contribute to these conditions. They propose that pycnogenol, a natural extract from pine bark, might help by reducing inflammation and improving gut bacteria balance, though more research is needed to prove this works.

This comprehensive review examines the pathological mechanisms underlying neurodevelopmental disorders (NDDs) including autism spectrum disorder, ADHD, and epilepsy, with particular focus on gut-brain axis disruption. The authors analyze how genetic susceptibility, environmental triggers, neurotransmitter dysregulation, and immune dysfunction contribute to NDD pathophysiology. Key signaling pathways (NF-κB, MAPK, PI3K/AKT/mTOR) are identified as strongly associated with NDD pathogenesis. The review proposes pycnogenol, a pine bark polyphenol extract, as a potential therapeutic intervention that may benefit NDDs through anti-inflammatory and antioxidant properties, while potentially modulating gut microbiome composition and metabolite production to influence gut-brain axis function.

The review highlights the importance of considering gut-brain interactions in NDD treatment. While pycnogenol shows theoretical promise as a natural intervention targeting inflammation and gut microbiome, clinical trials are needed to establish efficacy and safety in neurodevelopmental disorders before clinical application.

This is a narrative review rather than a systematic analysis of evidence. No specific studies of pycnogenol in NDDs are reported. The therapeutic potential of pycnogenol is largely theoretical based on its known properties rather than direct clinical evidence in neurodevelopmental disorders.

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 (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 ofand butyric acid-producing bacteria) and its metabolites, providing a new strategy for the treatment of NDDs.