Microbiota-gut-brain axis in cerebral palsy: from mechanisms to interventions

Cerebral palsy (CP) is the most common cause of chronic motor disability in childhood and arises from non-progressive injury to the developing brain. Despite the static nature of the primary lesion, children with CP frequently experience evolving gastrointestinal, nutritional, inflammatory, sleep, cognitive, and seizure-related comorbidities that substantially influence functional recovery and caregiver burden. The microbiota-gut-brain axis (MGBA) provides a biologically plausible framework linking these multisystem manifestations. Emerging evidence suggests that children with CP may exhibit reduced gut microbial diversity, depletion of short-chain fatty acid (SCFA)-producing taxa, enrichment of opportunistic bacteria, and microbiome remodeling related to diet, constipation, antiepileptic drug exposure, oral inflammation, and care patterns. Dysbiosis may interact with CP through epithelial barrier disruption, lipopolysaccharide translocation, systemic immune activation, altered tryptophan-kynurenine metabolism, abnormal bile acid and SCFA signaling, vagal and enteric nervous system pathways, hypothalamic-pituitary-adrenal axis dysregulation, and microglial priming. These mechanisms may create a self-reinforcing cycle in which early brain injury promotes gut dysfunction, gut dysfunction reshapes the microbiome, and dysbiotic immune-metabolic signals further amplify symptom burden. Current interventions, including nutritional optimization, constipation protocols, dietary fiber, probiotics, prebiotics, synbiotics, oral health management, and family-centered care, show promise for improving bowel symptoms and selected microbial or inflammatory indices. However, most clinical studies remain small, short-term, and focused on constipation rather than long-term neurodevelopmental outcomes. All CP-specific human evidence currently demonstrates association rather than causation; no study has established that dysbiosis initiates CP or causally drives its neurological phenotype. Accordingly, mechanistic pathways are presented as testable hypotheses, not validated causal mechanisms in CP. This review synthesizes current evidence on the MGBA in CP, outlines mechanistic pathways, evaluates therapeutic opportunities, and proposes future directions for biomarker-driven and stratified intervention trials.