Frontiers in microbiologySep 11, 2026

How Traditional Chinese Medicine Ingredients May Affect Gut-Brain Balance in Alzheimer's Disease

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

Updated Sep 12, 2026

Abstract

Increased short-chain fatty acid (SCFA) levels in vivo are associated with alleviating microglial dysfunction linked to aging.

Bioactive components from traditional Chinese medicine may protect neurons by regulating gut microbiota composition and maintaining intestinal barrier function.
Different types of stimuli can influence SCFA activities, with acetate inhibiting inflammation in microglia under mechanical stretch but not under LPS exposure.
Methodological issues in current research include the lack of documentation of absolute SCFA concentrations and insufficient verification of causal relationships.
The review suggests a shift from correlational analysis to mechanistic exploration for developing therapies targeting the gut-brain axis in Alzheimer's disease.

Simplified

Alzheimer's disease (AD) currently lacks curative treatments, and the gut-brain axis plays an important role in regulating neuroinflammation during AD progression. Multiple bioactive components from traditional Chinese medicine (TCM), including polysaccharides, alkaloids, flavonoids and saponins, protect neurons through regulating gut microbiota composition, maintaining intestinal barrier function and modulating short-chain fatty acid (SCFA) metabolism. Different from previous reviews that mainly elaborate correlational relationships, the present paper systematically sorts out a multi-level action network of TCM components along the gut-brain axis. We address an interesting discrepancy in current findings on SCFAs: acetate can inhibit inflammation in microglia under mechanical stretch, yet fails to produce the same effect under LPS exposure. Nevertheless, increased SCFA levels in vivo are able to alleviate microglial dysfunction linked to aging. Such findings indicate that SCFA activities are influenced by stimulus types, compound categories and applied doses, reminding researchers to treat existing conclusions with caution. We also outline six widely existing methodological issues in relevant researches, and propose feasible solutions, including the documentation of absolute SCFA concentrations, experimental verification of causal relationships, and the use of AD pathological stimuli like Aβ and tau. This review may facilitate the shift from correlational analysis to mechanistic exploration, and provide useful references for the development of AD therapies targeting the gut-brain axis with TCM components.

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How Traditional Chinese Medicine Ingredients May Affect Gut-Brain Balance in Alzheimer's Disease

Abstract

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