António E. Abreu1,2,3  · Nuno Empadinhas1,2  · Sandra Morais Cardoso1,2,3

1 CNC‑UC ‑ Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal 

2 CIBB ‑ Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal 

3 Faculty of Medicine, University of Coimbra, Coimbra, Portugal

Abstract

Butyrate, a short-chain fatty acid (SCFA) produced by gut microbiota, plays crucial roles in maintaining intestinal homeostasis and modulating the gut-brain axis. Dysbiosis and SCFA imbalances are increasingly recognized as contributors to disease pathogenesis. A decrease in butyrate-producing bacteria leads to reduced butyrate levels, which have been linked to increased intestinal permeability, systemic inflammation, and neuroinflammation. Emerging evidence highlights a potential therapeutic role for butyrate in Parkinson’s Disease (PD). This review examines butyrate’s origins, functions, and mechanisms in the gut, its impact on the gut-brain axis, and its relevance in both “brain-first” and “gut-first” PD models. We also explore the effects of butyrate supplementation in animal models and human clinical studies, highlighting its promise as a therapeutic agent for PD. The understanding of butyrate as a versatile metabolite may pave the way for innovative strategies to prevent or manage PD, stressing the need for integrated approaches targeting both the nervous and gastrointestinal systems.

Keywords

Butyrate; Short-chain fatty acid; Gut microbiota; Gut-brain axis; Parkinson’s disease; Dysbiosis; Neuroinflammation

[SpringerLink]