ArticleFrontiers in molecular neuroscience2026
Modulation of the microbiota-lipid-brain axis by modified Chaihu-Longgu-Muli Decoction ameliorates chronic stress-induced depression.
Article in Frontiers in molecular neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background and aims: Modified Chaihu-Longgu-Muli Decoction (mCLMD) has well-established clinical antidepressant efficacy, yet its precise systemic mechanisms of action remain incompletely characterized. Here, we employed an integrated multi-omics strategy to delineate the mechanisms by which mCLMD exerts antidepressant-like effects via modulation of the gut microbiota-lipid-brain axis. Experimental procedures: Rats exposed to chronic unpredictable mild stress (CUMS) were administered graded doses of mCLMD. Depressive-like behaviors were assessed using the sucrose preference test, forced swim test, and open field test. To delineate the underlying mechanisms, we integrated network pharmacology analysis, 16S rRNA gene sequencing, serum metabolomics, and targeted validation of hippocampal signaling pathways. Results: mCLMD administration dose-dependently reversed CUMS-induced depressive-like behaviors in rats. Consistent with network pharmacology predictions, 16S rRNA sequencing revealed that mCLMD ameliorated CUMS-induced gut dysbiosis, characterized by reduced relative abundance of pro-inflammatory genera ( Conclusion: The antidepressant effects of mCLMD are strongly associated with systemic remodeling of the gut microbiota-lipid-brain axis. These therapeutic effects potentially stem from both the direct pharmacological activity of mCLMD's bioactive compounds and indirect modulation of the gut microbiota and host metabolism. Collectively, our findings provide robust preclinical evidence underpinning the clinical application of mCLMD in the management of major depressive disorder.
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