A water-insoluble β-1,3-glucan (Wβ) with a molecular weight of 8.12 × 104 Da was extracted from an edible fungus Wolfiporia cocos. Its backbone was composed of 1,3-β-linked Glcp branched at the C-2, C-4, and C-6 positions, connecting more 1,3-β-linked Glcp with a triple helical structure. Wβ effectively ameliorated depressive symptoms, abnormality of neurotransmitters and inflammatory factors in chronic unpredictable mild stress (CUMS)-induced rats. Wβ also altered the composition of gut microbiota, especially Romboutsia, norank_f_Muribaculaceae and Ruminococcus. Integration of untargeted and targeted metabolomics and Western blotting analysis suggested that the short-chain fatty acids (SCFAs) and tryptophan metabolites were the most important metabolites involved in Wβ mediation. Wβ significantly modulated the levels of 7 SCFAs and 7 tryptophan metabolites, as well as the protein expression of two related enzymes (indoleamine-2,3-dioxygenase: IDO; kynurenine-3-monooxygenase: KMO). Our results suggest that Wβ exerts its antidepressant effect by influencing neurotransmitters and inflammatory factors through interactions between the gut microbiota, SCFA and tryptophan metabolites. The findings offer new insights into water-insoluble polysaccharides, especially β-glucan in structure analysis and utilization, and provide evidence that Wβ, a novel glucan from the often-discarded water-insoluble part of Wolfiporia cocos, has potential application in antidepressant health products.
Keywords: Depression; Gut microbiota; Short-chain fatty acids; Tryptophan metabolism; Wolfiporia cocos.
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