Erythritol as a functional food ingredient mitigates heat-induced renal injury in mice via integrated metabolomic and transcriptomic analysis

Global warming increases the risk of heat-related renal impairment, while higher ambient temperatures may increase overall fluid and beverage consumption to meet hydration demands. As erythritol is widely used as a dietary sweetener in food and beverage products and is primarily excreted via the kidneys, concerns have been raised regarding its renal effects, particularly under conditions of heat stress. Here, we used integrated metabolomic and transcriptomic analyses to explore erythritol's role in heat-induced renal injury in mice. Erythritol supplementation modulated oxidative stress, inflammation, and lipid metabolism, with metabolomics showing recovery of redox-related metabolites and transcriptomics revealing downregulation of pro-inflammatory genes (e.g., Cxcl9 , Serpina3g ) and stress chaperones, alongside upregulation of antioxidative genes (e.g., Gbp6 , Tgtp1 ). Multi-omics highlighted PPAR and AMPK pathways as key targets. Animal experiments confirmed improved renal histology, reduced creatinine, and decreased oxidative and inflammatory markers. These findings indicate that erythritol protects against heat-induced renal damage, supporting its potential as a functional food ingredient for thermally stressful conditions. • Erythritol alleviates heat-induced renal injury in a mouse model. • Erythritol reduces oxidative stress and inflammatory responses under heat. • Multi-omics reveal metabolic and transcriptional modulation by erythritol. • Erythritol shows potential as a functional ingredient under heat stress.