Molecules (Basel, Switzerland)Oct 27, 2026

Natural Compounds and Their Gut Microbe Products May Influence the Gut-Brain Link in Alzheimer’s Disease: Biochemical Mechanisms and Drug Development Insights

Gut-Brain Axis Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Oct 28, 2026

Abstract

Gut microbial dysbiosis is associated with neurodegenerative diseases through various mechanisms.

Oxidative stress, neuroinflammation, and disruption of the epithelial barrier are potential pathways linking gut microbiota to neurodegeneration.
Currently available therapies for neurodegenerative diseases mainly provide symptomatic relief without altering disease progression.
Natural bioactive compounds, especially polyphenols, may act as multi-target modulators of the microbiota-gut-brain axis.
The review discusses the effects of these natural compounds and their metabolites on microbial, epithelial, immune, and neural functions.
Alzheimer disease is highlighted as a key focus for exploring the therapeutic potential of MGBA modulation.

Simplified

The microbiota-gut-brain axis (MGBA) is a complex signaling network linking the gut microbiota with central nervous system function. Growing evidence suggests that gut microbial dysbiosis contributes to neurodegenerative diseases (NDs) through mechanisms involving oxidative stress, neuroinflammation, disruption of the epithelial barrier, and altered microbial metabolite production. Unfortunately, the currently available therapies for NDs remain predominantly focused on symptomatic relief and do not modify the underlying disease progression. Natural bioactive compounds, particularly polyphenols, have emerged as promising multi-target modulators of the MGBA due to their pleiotropic effects across microbial, epithelial, immune, and neural compartments. This narrative review summarizes the available evidence on natural compounds and their microbial metabolites that target the MGBA, as evaluated in both in vitro and in vivo models. With a focus on Alzheimer disease, the molecular and cellular mechanisms underlying their effects across microbial, epithelial, immune, and neural compartments, as well as their potential therapeutic value through MGBA modulation, are discussed.

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Natural Compounds and Their Gut Microbe Products May Influence the Gut-Brain Link in Alzheimer’s Disease: Biochemical Mechanisms and Drug Development Insights

Abstract

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