PMID- 38041095 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231205 IS - 1743-7075 (Print) IS - 1743-7075 (Electronic) IS - 1743-7075 (Linking) VI - 20 IP - 1 DP - 2023 Dec 1 TI - Amelioration of Atherosclerosis by lycopene is linked to the modulation of gut microbiota dysbiosis and related gut-heart axis activation in high-fat diet-fed ApoE(-/-) mice. PG - 53 LID - 10.1186/s12986-023-00772-x [doi] LID - 53 AB - BACKGROUND: Interplay between gut microbiota and heart, termed "gut-heart" axis, has a crucial role in the pathogenesis of atherosclerosis. Our previous study showed that lycopene possesses anti-inflammatory and anti-atherosclerotic effects, but its link to the gut microbiota is poorly understood. Herein, we surmised that lycopene could regulate the gut microbiota, exert anti-atherosclerotic effect by regulating the "gut-heart" axis. METHODS: Male ApoE(-/-) mice were fed a high-fat diet (HFD) with or without lycopene (0.1% w/w) for 19 weeks. Gut microbiota was analyzed by 16 S rRNA sequencing, the protein levels of zonula occludens-1 (ZO-1), occludin, toll-like receptor 4 (TLR4) and phospho-nuclear factor-kappaB (NF-kappaB) p65 were measured by Western blotting, the levels of serum inflammatory factors including monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 were assayed using ELISA kits. Also, the concentrations of serum lipopolysaccharide (LPS), D-lactic acid (D-LA) and diamine peroxidase (DAO) were measured through ELISA method. RESULTS: The aortic sinus sections revealed that lycopene supplementation significantly reduced the extent of atherosclerotic lesions and inhibited atherosclerosis development caused by HFD. The analysis of gut microbiota showed that lycopene reduced the ratio of Firmicutes/Bacteroides and increased the relative abundance of Verrucomicrobia, Akkermansia and Alloprevotella, which were related to elevated intestinal barrier function and reduced inflammation. Moreover, lycopene up-regulated the expression of intestinal ZO-1 and occludin and decreased serum LPS, D-LA and DAO levels. In addition, lycopene inhibited the expression of TLR4 and phospho-NF-kappaB p65 in aortic sinus plaque, serum MCP-1, TNF-alpha, IL-1beta, and IL-6 levels were also lowered by lycopene treatment. CONCLUSIONS: Our results indicated the protective effect of lycopene against atherosclerosis induced by HFD and further revealed that its mechanism might be its prebiotic effect on maintaining gut microbiota homeostasis and improving intestinal barrier function, consequently reducing serum LPS-triggered inflammatory response in the heart. CI - (c) 2023. The Author(s). FAU - Tu, Tengcan AU - Tu T AD - The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510280, China. AD - Department of Cardiology, The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, 120 Guidan Road, Foshan, 528200, Guangdong Province, China. FAU - Liu, Hao AU - Liu H AD - Department of Cardiology, The Seventh Affiliated Hospital of Southern Medical University, Foshan, 528244, China. FAU - Liu, Zhenhao AU - Liu Z AD - Department of Cardiology, Ganzhou People's Hospital, Ganzhou, 341000, China. FAU - Liang, Yunyi AU - Liang Y AD - Health Management Center, The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, 528200, China. FAU - Tan, Chujun AU - Tan C AD - The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510280, China. FAU - Feng, Dan AU - Feng D AD - Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China. fengdan3@mail.sysu.edu.cn. FAU - Zou, Jun AU - Zou J AD - The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510280, China. zoujun961@163.com. AD - Department of Cardiology, The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, 120 Guidan Road, Foshan, 528200, Guangdong Province, China. zoujun961@163.com. LA - eng GR - 81973019/National Natural Science Foundation of China/ GR - 2022A1515011610, 2020A1515011167/Natural Science Foundation of Guangdong Province/ GR - 2022A1515012268, 2018A030313782/Natural Science Foundation of Guangdong Province/ PT - Journal Article DEP - 20231201 PL - England TA - Nutr Metab (Lond) JT - Nutrition & metabolism JID - 101231644 PMC - PMC10691047 OTO - NOTNLM OT - Atherosclerosis OT - Gut microbiota OT - Lycopene OT - Nuclear factor-kappaB OT - Toll-like receptor 4 COIS- The authors declare no competing interests. All authors declare that they have no conflict of interest. EDAT- 2023/12/02 00:41 MHDA- 2023/12/02 00:42 PMCR- 2023/12/01 CRDT- 2023/12/01 23:58 PHST- 2023/08/11 00:00 [received] PHST- 2023/11/21 00:00 [accepted] PHST- 2023/12/02 00:42 [medline] PHST- 2023/12/02 00:41 [pubmed] PHST- 2023/12/01 23:58 [entrez] PHST- 2023/12/01 00:00 [pmc-release] AID - 10.1186/s12986-023-00772-x [pii] AID - 772 [pii] AID - 10.1186/s12986-023-00772-x [doi] PST - epublish SO - Nutr Metab (Lond). 2023 Dec 1;20(1):53. doi: 10.1186/s12986-023-00772-x.