The effects of polyphenols on gut microbial metabolites and composition in neurodegenerative diseases: a systematic review

Neurodegenerative diseases (NDDs) like Alzheimer’s disease (AD) and Parkinson’s disease (PD) are growing global health concerns characterized by progressive cognitive and motor impairments. Recent studies have reported the role of gut microbiota and its interaction with the microbiome-gut-brain axis (MGBA) in these disorders. Dietary polyphenols possess antioxidant and antiinflammatory properties, which might modulate gut microbiota and attenuate the progression of these NDDs by acting on MGBA. This systematic review evaluates the effects of polyphenols on gut microbiota, their metabolites, and gut microbiota-related mechanisms in NDDs. Following PRISMA guidelines, a comprehensive literature search was conducted across Embase, PubMed, Scopus, and Google Scholar databases. Studies investigating the effects of polyphenols on gut microbial metabolites and composition in NDDs were reviewed. Data were extracted on study design, interventions, and outcomes, and quality was assessed using SYRCLE’s risk of bias tool. Twenty-six animal studies met the inclusion criteria. Polyphenols favored microbial beneficial changes, increased short-chain fatty acids (SCFAs), and reduced neuroinflammation by modulating inflammatory cytokine profiles (IL-1β, TNF-α, and IL-6 reduction). In NDD animal models, memory and motor functions were observed to have improved, likely due to reduced oxidative stress, as well as decreased amyloid accumulation and improved gut and brain integrity. The interventions enriched beneficial genera (Bacteroidetes, Bifidobacterium, Lactobacillus, Rikenellaceae, and Alloprevotella) and reduced detrimental groups (Helicobacter, Bacteroidaceae, Rikenella, and Prevotella). The evidence suggests polyphenols may influence the gut microbiota and, in turn, alleviate NDD symptoms. However, we need to confirm this in more studies, especially in human studies.