Fucoxanthin Ameliorates Diabetic Kidney Disease via Modulating the Gut Microbiota and Tryptophan-Kynurenine Metabolic Pathway.

This study employs a multiomics approach to investigate the protective effects of fucoxanthin (Fu) and explore its potential association with metabolic and signaling pathways in diabetic mice induced by a high-fat diet combined with streptozotocin (STZ) administration. Diabetic model mice were randomly divided into normal control (NC), diabetic model, low-dose Fu (50 mg/kg/day), and high-dose Fu (100 mg/kg/day) groups. After 6 weeks of intervention, Fu treatment was associated with dose-dependent improvements in glucose and lipid metabolism, reduced oxidative stress, decreased expression of inflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], and IL-1β) and renal fibrosis markers (TGF-β1, α-SMA, and Col1a1), along with notable attenuation of renal pathological damage. Exploratory analyses indicated that these phenotypic improvements were accompanied by reduced renal IDO1 expression, favorable shifts in tryptophan (Trp) metabolism, and upregulated AhR/CYP1A1 signaling. 16S rRNA sequencing revealed that Fu treatment was associated with a restoration of diabetes-altered gut microbiota β-diversity. Serum metabolomics identified that Fu administration correlated with alterations in multiple metabolites (including 5'-S-methyl-5'-thioadenosine, LPC 16:0, and bile acids), which are linked to key pathways such as Trp metabolism and bile acid biosynthesis. Network pharmacology predictions further suggested potential multitarget interactions of Fu with the PI3K-Akt and AGE-RAGE signaling pathways. Collectively, these findings indicate that Fu exerts potential renoprotective effects in diabetic mice, which are accompanied by a normalization of Trp-AhR pathway-related metabolism and concurrent attenuation of inflammatory, oxidative, and fibrotic responses. While causal functional links remain to be fully elucidated, these observations provide a preliminary basis for further mechanistic investigation and support the potential of Fu as a dietary supplement or adjunctive strategy for diabetic kidney disease (DKD).