Fecal microbiota transplantation ameliorates atherosclerosis in mice with C1q/TNF-related protein 9 genetic deficiency
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Despite the strong influence of the gut microbiota on atherosclerosis, a causal relationship between atherosclerosis pathophysiology and gut microbiota is still unverified. This study was performed to determine the impact of the gut microbiota on the pathogenesis of atherosclerosis caused by genetic deficiency. To elucidate the influence of the gut microbiota on atherosclerosis pathogenesis, an atherosclerosis-prone mouse model (C1q/TNF-related protein 9-knockout (CTRP9-KO) mice) was generated. The gut microbial compositions of CTRP9-KO and WT control mice were compared. Fecal microbiota transplantation (FMT) was performed to confirm the association between gut microbial composition and the progression of atherosclerosis. FMT largely affected the gut microbiota in both CTRP9-KO and WT mice, and all transplanted mice acquired the gut microbiotas of the donor mice. Atherosclerotic lesions in the carotid arteries were decreased in transplanted CTRP9-KO mice compared to CTRP9-KO mice prior to transplantation. Conversely, WT mice transplanted with the gut microbiotas of CTRP9-KO mice showed the opposite effect as that of CTRP9-KO mice transplanted with the gut microbiotas of WT mice. Here, we show that CTRP9 gene deficiency is related to the distribution of the gut microbiota in subjects with atherosclerosis. Transplantation of WT microbiotas into CTRP9-KO mice protected against the progression of atherosclerosis. Conversely, the transplantation of CTRP9-KO microbiotas into WT mice promoted the progression of atherosclerosis. Treating atherosclerosis by restoring gut microbial homeostasis may be an effective therapeutic strategy.
Abstract
Despite the strong influence of the gut microbiota on atherosclerosis, a causal relationship between atherosclerosis pathophysiology and gut microbiota is still unverified. This study was performed to determine the impact of the gut microbiota on the pathogenesis of atherosclerosis caused by genetic deficiency. To elucidate the influence of the gut microbiota on atherosclerosis pathogenesis, an atherosclerosis-prone mouse model (C1q/TNF-related protein 9-knockout (CTRP9-KO) mice) was generated. The gut microbial compositions of CTRP9-KO and WT control mice were compared. Fecal microbiota transplantation (FMT) was performed to confirm the association between gut microbial composition and the progression of atherosclerosis. FMT largely affected the gut microbiota in both CTRP9-KO and WT mice, and all transplanted mice acquired the gut microbiotas of the donor mice. Atherosclerotic lesions in the carotid arteries were decreased in transplanted CTRP9-KO mice compared to CTRP9-KO mice prior to transplantation. Conversely, WT mice transplanted with the gut microbiotas of CTRP9-KO mice showed the opposite effect as that of CTRP9-KO mice transplanted with the gut microbiotas of WT mice. Here, we show that CTRP9 gene deficiency is related to the distribution of the gut microbiota in subjects with atherosclerosis. Transplantation of WT microbiotas into CTRP9-KO mice protected against the progression of atherosclerosis. Conversely, the transplantation of CTRP9-KO microbiotas into WT mice promoted the progression of atherosclerosis. Treating atherosclerosis by restoring gut microbial homeostasis may be an effective therapeutic strategy.
참고문헌 (43)
- Qin, J., "A human gut microbial gene catalogue established by metagenomic sequencing", Nature, 464, pp.59~65 (2010)
- Eckburg, P. B., "Diversity of the human intestinal microbial flora", Science, 308, pp.1635~1638 (2005)
- Clemente, J. C., "The impact of the gut microbiota on human health: an integrative view", Cell, 148, pp.1258~1270 (2012)
- Wang, J., "Metagenome-wide association studies : fine-mining the microbiome", Nat. Rev. Microbiol, 14, pp.508~522 (2016)
- Dabke, K., "The gut microbiome and metabolic syndrome", J. Clin. Invest, 129, pp.4050~4057 (2019)
- Aron-Wisnewsky, J., "The gut microbiome, diet, and links to cardiometabolic and chronic disorders", Nat. Rev. Nephrol, 12, pp.169~181 (2016)
- Tang, W. H., "Gut microbiota in cardiovascular health and disease", Circ. Res, 120, pp.1183~1196 (2017)
- Dahlof, B., "Cardiovascular disease risk factors: epidemiology and risk assessment", Am. J. Cardiol, 105, pp.3A~9A (2010)
- Hansson, G. K., "Inflammation, atherosclerosis, and coronary artery disease", N. Engl. J. Med, 352, pp.1685~1695 (2005)
- Gimbrone, M. A. Jr., "Endothelial dysfunction, hemodynamic forces, and atherogenesis", Ann. Ny. Acad. Sci, 902, pp.230~239 (2000)[DOI]
- Koren, O., "Human oral, gut, and plaque microbiota in patients with atherosclerosis", Proc. Natl Acad. Sci. USA, 108, pp.4592~4598 (2011)[DOI]
- Fak, F., "Oral microbiota in patients with atherosclerosis", Atherosclerosis, 243, pp.573~578 (2015)
- Karlsson, F. H., "Symptomatic atherosclerosis is associated with an altered gut metagenome", Nat. Commun, 3, pp.1245~ (2012)
- Tang, W. H., "Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk", N. Engl. J. Med, 368, pp.1575~1584 (2013)
- Ierardi, E., "Intestinal microbial metabolism of phosphatidylcholine : a novel insight in the cardiovascular risk scenario", Hepatobiliary. Surg. Nutr, 4, pp.289~292 (2015)
- Koeth, R. A., "Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis", Nat. Med, 19, pp.576~585 (2013)
- Yamashita, T., "Intestinal Immunity and Gut Microbiota in Atherogenesis", J. Atheroscler. Thromb, 24, pp.110~119 (2017)
- Kirchgesner, J., "Increased risk of acute arterial events in young patients and severely active IBD : a nationwide French cohort study", Gut, 67, pp.1261~1268 (2018)
- Wong, G. W., "A family of Acrp30", adiponectin structural and functional paralogs, 2004, pp.101, 10302~10307
- Wong, G. W., "Molecular, biochemical and functional characterizations of C1q", TNF family members : adipose-tissue-selective expression patterns, regulation by PPAR-gamma agonist, cysteine-mediated oligomerizations, combinatorial associations and metabolic functions, 2008, pp.416, 161~177
- Peterson, J. M., "CTRP1 protein enhances fatty acid oxidation via AMP-activated protein kinase(AMPK)activation and acetyl-CoA carboxylase(ACC)inhibition", J. Biol. Chem, 287, pp.1576~1587 (2012)
- Lu, L., "C1q", TNF-related protein-1 : an adipokine marking and promoting atherosclerosis, 2016, pp.37, 1762~1771
- Yi, W., "Reduced cardioprotective action of adiponectin in high-fat dietinduced type II diabetic mice and its underlying mechanisms", Antioxid. Redox Signal, 15, pp.1779~1788 (2011)
- Su, H., "Inhibition of CTRP9, a novel and cardiac-abundantly expressed cell survival molecule, by TNFalpha-initiated oxidative signaling contributes to exacerbated cardiac injury in diabetic mice", Basic. Res. Cardiol, 108, pp.315~ (2013)
- Zheng, Q., "C1q", TNF-related proteins, a family of novel adipokines, induce vascular relaxation through the adiponectin receptor-1, eNOS, pp.nitric oxide signaling pathway, Arterioscler. Thromb. Vasc. Biol[DOI]
- Wang, H., "One-step generation of mice carrying mutations in multiple genes by CRISPR", Cas-mediated genome engineering, 2013, pp.153, 910~918
- Kwon, S., "CASPER : context-aware scheme for paired-end reads from high-throughput amplicon sequencing", BMC Bioinforma, 15, pp.S10~ (2014)[DOI]
- Bokulich, N. A., "Quality-filtering vastly improves diversity estimates from Illumina amplicon sequencing", Nat. Methods, 10, pp.57~59 (2013)
- Rognes, T., "VSEARCH : a versatile open source tool for metagenomics", PeerJ, 4, pp.e2584~ (2016)
- Quast, C., "The SILVA ribosomal RNA gene database project : improved data processing and web-based tools", Nucleic Acids Res, 41, pp.D590~D596 (2013)
- Caporaso, J. G., "QIIME allows analysis of high-throughput community sequencing data", Nat. Methods, 7, pp.335~336 (2010)
- Ericsson, A. C., "Variable colonization after reciprocal fecal microbiota transfer between mice with low and high richness microbiota", Front. Microbiol, 8, pp.196~ (2017)
- Nam, D., "Partial carotid ligation is a model of acutely induced disturbed flow, leading to rapid endothelial dysfunction and atherosclerosis", Am. J. Physiol. Heart Circ. Physiol, 297, pp.H1535~H1543 (2009)
- Toledo-Flores, D., "Vasculogenic properties of adventitial Sca-1(+)CD45(+)progenitor cells in mice : a potential source of vasa vasorum in atherosclerosis", Sci. Rep, 9, pp.7286~ (2019)
- Li, J., "Akkermansia muciniphila protects against atherosclerosis by preventing metabolic endotoxemia-induced inflammation in Apoe-", - mice, 2016, pp.133, 2434~2446
- Yoshida, N., "Bacteroides vulgatus and Bacteroides dorei reduce gut microbial lipopolysaccharide production and inhibit atherosclerosis", Circulation, 138, pp.2486~2498 (2018)
- Jung, C. H., "C1q", TNF-related protein-9 inhibits cytokine-induced vascular inflammation and leukocyte adhesiveness via AMP-activated protein kinase activation in endothelial cells, 2016, pp.419, 235~243
- Wong, G. W., "Identification and characterization of CTRP9, a novel secreted glycoprotein, from adipose tissue that reduces serum glucose in mice and forms heterotrimers with adiponectin", FASEB J, 23, pp.241~258 (2009)
- Wang, X. Q., "C1q", TNF-related protein 1 links macrophage lipid metabolism to inflammation and atherosclerosis, 2016, pp.250, 38~45
- Libby, P., "Inflammation and atherosclerosis", Circulation, 105, pp.1135~1143 (2002)
- Hug, C., "T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30", adiponectin, 2004, pp.101, 10308~10313
- Kambara, T., "C1q", tumor necrosis factor-related protein 9 protects against acute myocardial injury through an adiponectin receptor I-AMPK-dependent mechanism, 2015, pp.35, 2173~2185
- Yoneda, K., "Expression of adiponectin receptors, AdipoR1 and AdipoR2, in normal colon epithelium and colon cancer tissue", Oncol. Rep, 20, pp.479~483 (2008)