Dietary nisin exacerbates diabetic vascular complications through gut microbiota modulation and NF-κB signaling

Diabetic vascular complications (DVCs) are a major cause of morbidity in diabetes, with gut microbiota dysbiosis emerging as an important contributor. This study investigates the impact of nisin, a widely used food preservative, on DVCs using a zebrafish model. We found that nisin exacerbates diabetic vascular pathology in zebrafish through gut microbiota-dependent mechanisms. Nisin treatment induced dysbiosis with enrichment of Gram-negative pathogens and intestinal barrier disruption. Concurrently, it elevated systemic oxidative stress and pro-inflammatory cytokines, accompanied by NF-κB pathway activation. Germ-free zebrafish experiments confirmed the gut microbiota's essential role in nisin-induced vascular injury. Pharmacological inhibition of NF-κB reversed nisin's effects, restoring endothelial function and hemodynamics. Our findings reveal a previously unrecognized risk of nisin consumption in diabetic individuals and highlight the gut-vascular axis as a therapeutic target for DVCs.