摘要:Hyperlipidemia is associated with chronic inflammation and intestinal dysbiosis. The purpose of this study was to investigate the protective effect of Nostoc sphaeroids Kütz (NO) on diet‐induced hyperlipidemia in mice. Experimental animals received a high‐fat diet (HFD) for 4 weeks, then an HFD supplemented with 2.5% or 7.5% NO for 6 weeks. HFD‐fed mice exhibited a significant increase in serum total cholesterol, triglycerides, and low‐density lipid cholesterol, and a decrease in high‐density lipid cholesterol. NO supplementation was associated with significantly lower dyslipidemia, decreased intestinal inflammation, and inhibition of toll‐like receptor 4 gene repression in HFD‐fed mice. Results suggest that NO treatment protected the integrity of the intestinal barrier. NO treatment was also associated with significant changes in the intestinal microbiota induced by HFD and an increase in the Firmicutes‐to‐Bacteroidetes ratio. Furthermore, NO treatment was also inversely correlated with mice obesity and hyperlipidemia NO and was associated with no significant in fecal short‐chain fatty acids. In conclusion, NO significantly ameliorated hyperlipidemia induced by a HFD in mice, potentially via a decrease intestinal inflammation, increase in intestinal barrier integrity, and amelioration in the gut microbiota.