Lactobacillus reuteri DSM17938 and its supernatant ameliorate parkinson's disease: insights from multi-omics and network pharmacology

ABSTRACT:

The mechanisms by which probiotics ameliorate neurodegenerative diseases have garnered significant scientific interest, yet elucidating their underlying pathways remains challenging. In this study, we establish an integrated multi-omics and network pharmacology strategy to unravel the protective mechanism of Lactobacillus reuteri DSM17938 and its supernatant in a Parkinson’s disease mice model. This work is intended as an initial step toward a more comprehensive understanding of how probiotics alleviate neurodegenerative diseases through gut microbiota and metabolism regulation. Given these findings, our research aligns well with the scope of Microbiome.

Based on the integrated approach incorporating gut microbiota analysis, untargeted metabolomics, network pharmacology, and molecular dynamics simulations, this study revealed that Lactobacillus reuteri DSM17938 and its supernatant treatment alleviate Parkinson's disease through the following aspects: (1) Improved motor function, reduced neuroinflammation and oxidative stress, and protection of dopaminergic neurons; (2) The treatment modulated the gut microbiota, promoted the accumulation of xanthurenic acid in the gut; (3) Furthermore, ADME analysis indicated that xanthurenic acid can cross the blood-brain barrier, and network pharmacology and molecular docking suggested that it may activate the aryl hydrocarbon receptor (AhR), thereby underlying its anti-PD effects; (4) Molecular dynamics simulations and free energy calculations confirmed the stable binding between xanthurenic acid and AhR, demonstrating high binding affinity with the key residue PHE-133.

The results of this article provide valuable insights by highlighting the crucial role of the gut-derived tryptophan metabolite xanthurenic acid in the neuroprotective effects of Lactobacillus reuteri DSM 17938 and its supernatant against Parkinson's disease. By integrating multi-omics, network pharmacology, molecular docking, and molecular dynamics simulations, we identified the AhR as a key target through which xanthurenic acid ameliorates PD.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

PROVIDER: MTBLS13169 | MetaboLights | 2025-10-18

REPOSITORIES: MetaboLights