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The gut microbiome and brain communicate through various pathways, including the vagus nerve, the immune system, and in situ generation of microbial metabolites. Among these metabolites, short-chain fatty acids (SCFAs) have received attention for their potential effects on Parkinson’s disease pathophysiology. However, the exact mechanisms and outcomes of SCFAs in Parkinson’s disease preclinical models are not yet fully understood.

In their review, “,” published in Redox Biology, co-authors Balaraman Kalyanaraman, PhD, professor of biophysics and the Harry R. & Angeline E. Quadracci Professor in Parkinson’s Research; Gang Cheng, PhD, assistant professor of biophysics; and Micael Hardy, PhD, of Aix-Marseille Université, France, explore the connecting pathways between SCFAs in the gut microbiome, the gut–brain axis, the aggregation of alpha-synuclein, the paradoxical effects of SCFAs on preclinical animal models of PD, neuroinflammation, and the formation of reactive oxygen and nitrogen species, as well as their epigenetic regulation of gene expression. Recent research has shown that alpha-synuclein and the misfolded protein may be used as a very early biomarker of Parkinson’s disease. Elucidating the role of SCFAs in the gut microbiome and their impact on alpha-synuclein-induced neuroinflammation in microglia and on reactive oxygen and nitrogen species is crucial in Parkinson’s disease pathogenesis and treatment.