The gut microbiota-metabolite-target axis in insomnia: network pharmacology and gut microbiota profiling insights into pathogenesis and intervention with Cinnamomi Cortex-Gardeniae Fructus.

Authors

Jiaquan Yuan, Dongyang Wu, Haoyang Xu, Junyao Jiao, Chen Yang, Xiucai Wu, Weifeng Liu, Erwei Hao

Published in

Frontiers in microbiology. Volume 17. Pages 1830736. Epub Jun 29, 2026.

Abstract

To investigate the mechanism underlying the association between gut microbiota metabolites and insomnia, focusing on the "gut microbiota-metabolite-target" axis. The Cinnamomi Cortex-Gardeniae Fructus (CC-GF) combination was used as an intervention.
Network pharmacology was applied to predict insomnia-related gut microbiota metabolites and their targets. A PCPA-induced rat insomnia model was established, and gut microbiota dysbiosis was validated using 16S rRNA sequencing. Core gut microbiota were identified, and core targets were screened via protein-protein interaction (PPI) network analysis and multi-algorithm ranking. A "core microbiota-metabolite-core target" network was constructed, and binding affinities were verified using molecular docking and molecular dynamics simulations.
Twenty-eight targets were predicted, and CASP3, NFE2L2, HDAC1, and CCND1 were identified as core targets related to oxidative stress, apoptosis, epigenetic regulation, and circadian disturbance. In the insomnia model, the beneficial genera Bifidobacterium and Bacteroides were decreased, whereas the harmful genera Ruminococcus and Blautia were increased. Nine key metabolites were identified; folic acid exhibited the strongest binding affinity to the core targets (average -8.83 kcal/mol) and was defined as the core metabolite. CC-GF reversed these microbiota alterations, confirming the regulatory role of this axis.
This study elucidates the "gut microbiota-metabolite-target" axis in insomnia and highlights the "Bifidobacterium-folic acid-target" pathway as a core mechanism. CC-GF intervention provides experimental evidence supporting this axis as a target for insomnia treatment.

PMID:
42445495
Bibliographic data and abstract were imported from PubMed on 14 Sep 2026.

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