Long-term sucralose exposure accelerates ovarian aging via gut microbiota dysbiosis

Abstract The increasing prevalence of obesity, diabetes, and other metabolic disorders is driving the application of sucralose in the food industry. However, its direct effects on the reproductive function have not been sufficiently investigated. Chronic sucralose consumption may induce ovarian aging, leading to ovarian dysfunction. This occurs in association with intestinal dysbiosis and disruption of intestinal tight junctions caused by prolonged intake of sucralose. These changes increase the production of lipopolysaccharide (LPS), which is derived from gram-negative bacteria, and facilitate its translocation into the systemic circulation. Circulating LPS binds to TLR4 in ovarian granulosa cells, activating the NF-κB signaling pathway. This activation triggers the nuclear translocation of the p65 subunit and increases the transcription of downstream inflammatory cytokines. Moreover, Baicalin methyl ester may serve as an early intervention strategy. It can significantly attenuate both intestinal and ovarian inflammatory damage induced by sucralose, primarily by inhibiting the TLR4/NF-κB pathway.