Polyphenols, Bioactive Peptides, and Pectin-Derived Oligosaccharides Show Promise for Brain Health via Microbiota-Gut-Brain Axis

Neurodegenerative and neuroinflammatory conditions like Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis are increasingly linked to dysregulation of the microbiota-gut-brain axis. This disruption often involves reduced beneficial gut microbes, impaired short-chain fatty acid production, and compromised intestinal and blood-brain barrier integrity, leading to chronic inflammation. Current treatments often fall short in addressing these multifaceted issues, creating a critical need for novel, microbiota-targeted dietary interventions that can restore balance and mitigate disease progression.

This comprehensive review synthesized current evidence on polyphenols, bioactive peptides, and pectin-derived oligosaccharides (POS) as prebiotic or prebiotic-like compounds. The authors focused on their potential activity through the microbiota-gut-brain axis in the context of neurodegenerative and demyelinating diseases. Particular attention was given to understanding the structure-function relationships of these compounds, their host-microbe interactions, and methods for their sustainable recovery from food by-products. The review aimed to consolidate findings from both preclinical and early clinical studies.

Preclinical studies consistently suggest that these bioactives may significantly reduce microglial activation, improve mitochondrial function, and strengthen both intestinal and blood-brain barrier integrity. These improvements correlate with enhanced cognitive or motor performance in various models. Early clinical studies, though limited, indicate possible benefits on mood, selected cognitive outcomes, metabolic regulation, and inflammatory biomarkers. Key mediators identified include microbiota-derived metabolites from polyphenols, such as urolithins, alongside glycomacropeptide and POS. These compounds appear to exert their effects by modulating gut microbiota composition and function, subsequently influencing systemic and central nervous system inflammation. For instance, urolithins, produced by gut bacteria from ellagitannins, have shown potent anti-inflammatory and neuroprotective properties. Glycomacropeptide, a milk-derived peptide, has demonstrated immunomodulatory effects. The review underscores the consistent observation that these compounds positively influence markers of neuroinflammation and neuronal health.

Microbiota-derived metabolites from polyphenols, such as urolithins, together with glycomacropeptide and POS, appear to be key mediators in improving brain health outcomes.