Prebiotics attenuate depressive-like behavior, neuroinflammation and synaptic plasticity in Parkinson’s disease by modulating butyrate-producing gut bacteria

Mar 13, 2026Inflammopharmacology

Prebiotics may reduce depression, brain inflammation, and nerve cell changes in Parkinson's by boosting helpful gut bacteria that produce butyrate

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Abstract

FOS and GOS administration significantly increased levels of serum and brain butyrate in a rotenone-induced Parkinson's disease model.

Approximately 40% of Parkinson's disease patients experience depression, affecting their quality of life.
FOS and GOS treatment relieved motor symptoms and depressive-like behavior in the model.
Increased brain serotonin and its receptor were observed following FOS and GOS administration.
Prebiotics reduced intestinal α-synuclein accumulation, decreased inflammation, and improved tight junction protein expression.
FOS and GOS attenuated dopaminergic neuron loss and reduced neuroinflammation markers in the substantia nigra and prefrontal cortex.
The treatment also promoted neuroplasticity by enhancing the expression of butyrate receptors and synaptic proteins.

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Parkinson's disease (PD) remains a challenging disease for treatment, which is usually polypharmacological. In addition to motor symptoms, non-motor symptoms such as depression are present in approximately 40% of patients, contributing to the loss of quality of life. In the last two decades, a growing body of evidence has emerged regarding the involvement of the microbiota-gut-brain axis in both PD and depression. Fructooligosaccharides (FOS) and galactooligosaccharides (GOS) are prebiotic fibers that can be fermented by the gut microbiota, which produce metabolites called short-chain fatty acids (SCFAs), whose effects can contribute to improvement in neurodegenerative and psychiatric conditions. This study analyzed the effects of FOS and GOS administration in a rotenone-induced PD model and demonstrated a relief of motor symptoms and depressive-like behavior, followed by an increase of brain serotonin and its respective receptor (SERT). FOS and GOS treatment also led to an increase in SCFAs-producing gut bacteria with significantly higher levels of serum and brain butyrate. Furthermore, in the intestine, prebiotics reduced the accumulation of α-synuclein, decreased inflammation, and improved the expression of zonula occludens and occludin. FOS and GOS also attenuated the loss of dopaminergic neurons and reduced neuroinflammation by decreasing α-synuclein, IBA-1, GFAP, iNOS, p-NFkB, and IL1-β levels in the substantia nigra and prefrontal cortex. In addition, these prebiotics improved neuroplasticity by promoting the expression of butyrate receptors (GPR43 and GPR109), BDNF, p-CREB, and synaptic protein PSD-95. In conclusion, FOS and GOS administration attenuatted depressive-like behavior, neuroinflammation, and synaptic plasticity in Parkinson's disease by modulating butyrate-producing gut bacteria.