Metabolomic-microbiomic integrated analysis reveals the role of intermittent energy restriction in Parkinson's disease.

Abstract

Aims: This study aimed to explore the neuroprotective effect of intermittent energy restriction (IER) on Parkinson's disease (PD) mice via multiomics.

Methods: All mice were randomly divided into four groups: the control group, the PD model group, the PD+IER group and the PD+L-Dopa group. A multi-omics strategy combining 16S rRNA sequencing and fecal metabolomics, together with molecular biological validation (Western blotting and immunohistochemistry), was employed to systematically investigate the protective effects of IER against PD in mice and the underlying mechanisms.

Results: The results showed that IER significantly reshaped the gut microbiota structure of PD mice, with enrichment of Clostridia and Peptostreptococcaceae. Metabolomic analysis further revealed that IER elevated the levels of beneficial intestinal metabolites mainly by regulating the GnRH secretion pathway and the serotonergic synaptic pathway, as well as by modulating signal transduction and amino acid metabolism. Notably, IER simultaneously decreased the expression of Parkin and HIF-1α in both intestinal and brain tissues.

Conclusions: The present study demonstrates that IER exerts neuroprotective effects to delay PD progression by regulating the gut microbiota-metabolite axis and targeting key proteins involved in PD pathogenesis. These findings provide experimental evidence and novel mechanistic insights into dietary intervention for PD.