Dietary sulforaphane glucosinolate alleviates stress–induced depression and demyelination through gut–brain axis modulation

Chronic stress is a major risk factor for depression and white matter injury, yet effective preventive strategies remain limited. Here, we investigated whether an 8-week diet supplemented with 0.1% sulforaphane glucosinolate (SGS) could prevent depression-like behaviors and corpus callosum (CC) demyelination in C57BL/6 mice exposed to 14 d of chronic restraint stress (CRS). SGS pre-treatment significantly reduced immobility in the forced swim test and showed a trend toward preserving sucrose preference compared with stressed controls. Consistently, Black-Gold II staining and myelin basic protein (MBP) immunofluorescence demonstrated that SGS markedly attenuated CRS-induced myelin loss in the corpus callosum. Gut microbiota profiling by 16S rRNA sequencing revealed unchanged α-diversity but clear β-diversity shifts, including enrichment of taxa such as Lacrimispora and Roseburia in SGS-fed mice under CRS. Untargeted plasma metabolomics further showed that SGS normalized stress-elevated metabolites, and correlation analyses linked specific microbial taxa and metabolites to myelin integrity. Together, these findings indicate that dietary SGS confers stress resilience and preserves white matter integrity, at least in part, through modulation of the gut-brain axis. SGS therefore represents a promising nutraceutical strategy for the prevention of stress-related neuropsychiatric and white matter disorders.