Huanglian Wendan decoction modulates gut microbiota-brain axis for depression comorbid with insomnia: a mini review

Depression comorbid with insomnia (DCI) is a highly prevalent mental disorder with complex pathogenesis, posing great clinical challenges for Western medical interventions due to adverse reactions, drug dependence and single targets. Accumulating preclinical evidence confirms the microbiota-gut-brain axis (MGBA) as a core regulatory hub in DCI pathogenesis, with gut microbiota dysbiosis being the initiating factor that disrupts host neuroendocrine, immune and circadian systems via multiple pathways, forming a vicious circle to aggravate DCI symptoms. Huanglian Wendan Decoction (HLWDD), a classic traditional Chinese medicine herbal formula, shows potential therapeutic effects on DCI by targeting the gut microbiota-the core node of MGBA. Notably, most relevant evidence is derived from animal preclinical models. This Mini Review succinctly summarizes the core pathological mechanisms of gut microbiota dysbiosis inducing DCI via MGBA, and elaborates HLWDD's multi-target therapeutic effects on DCI centered on gut microbiota regulation: reshaping gut microbiota composition, promoting short-chain fatty acids (SCFAs) production, and protecting intestinal mucosal barrier integrity, as well as improving central nervous system dysfunction via MGBA bidirectional regulation. We also discuss the existing academic controversies, critical research gaps and potential future development directions in this field. This review highlights the gut microbiota as a key therapeutic target of HLWDD for DCI, and provides a scientific basis for its clinical application and translational research via MGBA modulation.