The gut microbiota-short-chain fatty acid-inflammation axis in Parkinson's disease motor dysfunction: mechanisms and future of dietary interventions

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized mainly by motor dysfunction that severely affects quality of life. In recent years, the gut microbiota and its metabolites, short-chain fatty acids (SCFAs), have become a focus in PD research. These factors are proposed to influence disease progression, potentially by modulating neuroinflammation and gut-brain axis signaling, although the causal relationship between specific microbial metabolites and clinical deterioration remains to be conclusively demonstrated in human studies. PD patients show characteristic gut dysbiosis, with fewer beneficial SCFA-producing bacteria and more pro-inflammatory bacteria, which may drive disease progression via the gut-brain axis. Dietary interventions can regulate the gut microbiota, increase SCFA levels, and reduce inflammation, and have shown promise for improving motor symptoms in PD. This review summarizes the current understanding of the “gut microbiota-SCFA-inflammation axis” in PD motor dysfunction, focusing on the potential mechanisms by which specific dietary strategies-prebiotics, probiotics, and the Mediterranean diet, and emerging patterns such as ketogenic diets (KD) and intermittent fasting (IF)-may ameliorate motor symptoms through modulation of this axis, while critically appraising the limitations and inconsistencies in the existing literature. By integrating disease-specific mechanistic insights with a translational evaluation of dietary interventions, this Review aims to complement existing immunological frameworks with a clinically oriented perspective on PD motor dysfunction. We also integrate recent preclinical and clinical evidence, discuss current research limitations, and offer perspectives on future therapeutic directions.