Short-Chain Fatty Acids and Related Postbiotic Mediators in Neurodegenerative Diseases

Shazia Ansari¹, Gursimran Singh¹, Jemimol Solomon¹, Simranpreet Kaur¹, Khadga Raj Aran^1,2,*
1 Department of Pharmacy Practice, ISF College of Pharmacy, Moga, Punjab, India
2 Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, India
* Corresponding Author: Khadga Raj Aran. Email: email
(This article belongs to the Special Issue: Gut Microbiota-Derived Molecules and Cellular Mechanisms in Host Health and Disease)

BIOCELL https://doi.org/10.32604/biocell.2026.082358

Received 14 March 2026; Accepted 03 June 2026; Published online 24 June 2026

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Abstract

Neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s Disease (PD), and Multiple sclerosis (MS) represent a growing global health burden characterized by progressive neuronal loss, chronic neuroinflammation, immune dysregulation, and metabolic dysfunction. Increasing evidence highlights the gut-brain-immune axis as a critical regulator of disease susceptibility and progression. Microbiota-derived short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate, act as key postbiotic mediators that link intestinal microbial activity to the central nervous system. SCFAS modulates neurodegenerative pathways by regulating glial activation, inflammatory signaling, barrier integrity, and epigenetic and metabolic processes. Altered SCFAS production is consistently associated with neuroinflammation, barrier dysfunction, and disease progression. This review aims to synthesize current mechanistic and translational evidence on SCFAs in neurodegeneration by discussing shared and disease-specific pathways and emerging therapeutic and biomarker applications. Preclinical and early clinical studies suggest that restoring SCFAS signaling may influence disease pathways; its disease-modifying effects in humans remain scarce. These findings support further investigation of SCFAs with precision and microbiota-targeted strategies.