Lycopene protects against high-fat diet-induced atherosclerosis via modulating gut microbiota dysbiosis and related gut-heart axis activation in ApoE −/− mice

Abstract

Abstract Objective Lycopene possesses anti-atherosclerotic effects with molecular mechanism not fully identified. This study aimed to explore whether lycopene could regulate gut microbiota, exert anti-inflammatory and anti-atherosclerotic effects by modulating the “gut-heart” axis. Methods Male ApoE−/− mice were fed a high-fat diet (HFD) with or without lycopene for 19 weeks. Gut microbiota was analyzed by 16S rRNA sequencing, the protein levels of zonula occludens-1 (ZO-1), occludin, toll-like receptor 4 (TLR4) and phospho-nuclear factor-kappa B (NF-κB) p65 were measured by Western blotting. Results Lycopene supplementation significantly lowered serum lipid levels and reduced atherosclerotic lesions. Additionally, lycopene reduced the ratio of Firmicutes/Bacteroides and increased the relative abundance of gut microbiota related to elevated intestinal barrier function and reduced inflammation, including Verrucomicrobia, Akkermansia and Alloprevotella. Moreover, lycopene up-regulated the expression of intestinal tight junction proteins ZO-1 and occludin, decreased intestinal permeability and serum lipopolysaccharide levels. Lycopene also inhibited the expression of TLR4 and phospho-NF-κB p65 in aortic sinus plaque. Conclusion Our results indicated that the protective effect of lycopene against atherosclerosis induced by HFD and further revealed that its mechanism might be its prebiotic effect on maintaining intestinal flora homeostasis and improving intestinal barrier function, consequently reducing serum lipopolysaccharide-triggered inflammatory response in the heart.