nature.com

Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis - Nature Medicine

  • ️Hazen, Stanley L
  • ️Sun Apr 07 2013
  • Bernstein, A.M. et al. Major dietary protein sources and risk of coronary heart disease in women. Circulation 122, 876–883 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Micha, R., Wallace, S.K. & Mozaffarian, D. Red and processed meat consumption and risk of incident coronary heart disease, stroke, and diabetes mellitus: a systematic review and meta-analysis. Circulation 121, 2271–2283 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  • Siri-Tarino, P.W., Sun, Q., Hu, F.B. & Krauss, R.M. Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease. Am. J. Clin. Nutr. 91, 535–546 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bibbins-Domingo, K. et al. Projected effect of dietary salt reductions on future cardiovascular disease. N. Engl. J. Med. 362, 590–599 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hansen, E.S. International Commission for Protection Against Environmental Mutagens and Carcinogens. ICPEMC Working Paper 7/1/2. Shared risk factors for cancer and atherosclerosis–a review of the epidemiological evidence. Mutat. Res. 239, 163–179 (1990).

    Article  CAS  PubMed  Google Scholar 

  • Turnbaugh, P.J. et al. A core gut microbiome in obese and lean twins. Nature 457, 480–484 (2009).

    Article  CAS  PubMed  Google Scholar 

  • Turnbaugh, P.J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027–1031 (2006).

    Article  PubMed  Google Scholar 

  • Goodman, A.L. & Gordon, J.I. Our unindicted coconspirators: human metabolism from a microbial perspective. Cell Metab. 12, 111–116 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, Z. et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472, 57–63 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bremer, J. Carnitine—metabolism and functions. Physiol. Rev. 63, 1420–1480 (1983).

    Article  CAS  PubMed  Google Scholar 

  • Rebouche, C.J. & Seim, H. Carnitine metabolism and its regulation in microorganisms and mammals. Annu. Rev. Nutr. 18, 39–61 (1998).

    Article  CAS  PubMed  Google Scholar 

  • Brass, E.P. Carnitine and sports medicine: Use or abuse? Ann. NY Acad. Sci. 1033, 67–78 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Stanley, C.A. Carnitine deficiency disorders in children. Ann. NY Acad. Sci. 1033, 42–51 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Demarquoy, J. et al. Radioisotopic determination of l-carnitine content in foods commonly eaten in western countries. Food Chem. 86, 137–142 (2004).

    Article  CAS  Google Scholar 

  • Rigault, C., Mazue, F., Bernard, A., Demarquoy, J. & Le Borgne, F. Changes in l-carnitine content of fish and meat during domestic cooking. Meat Sci. 78, 331–335 (2008).

    Article  CAS  PubMed  Google Scholar 

  • Ley, R.E. et al. Evolution of mammals and their gut microbes. Science 320, 1647–1651 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Muegge, B.D. et al. Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans. Science 332, 970–974 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zimmer, J. et al. A vegan or vegetarian diet substantially alters the human colonic faecal microbiota. Eur. J. Clin. Nutr. 66, 53–60 (2012).

    Article  CAS  PubMed  Google Scholar 

  • Wu, G.D. et al. Linking long-term dietary patterns with gut microbial enterotypes. Science 334, 105–108 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rakoff-Nahoum, S., Paglino, J., Eslami-Varzaneh, F., Edberg, S. & Medzhitov, R. Recognition of commensal microflora by Toll-like receptors is required for intestinal homeostasis. Cell 118, 229–241 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Ley, R.E. et al. Obesity alters gut microbial ecology. Proc. Natl. Acad. Sci. USA 102, 11070–11075 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Febbraio, M. et al. Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice. J. Clin. Invest. 105, 1049–1056 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Suzuki, H. et al. A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection. Nature 386, 292–296 (1997).

    Article  CAS  PubMed  Google Scholar 

  • Brown, M.S. & Goldstein, J.L. The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell 89, 331–340 (1997).

    Article  CAS  PubMed  Google Scholar 

  • Spann, N.J. et al. Regulated accumulation of desmosterol integrates macrophage lipid metabolism and inflammatory responses. Cell 151, 138–152 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rader, D.J. Regulation of reverse cholesterol transport and clinical implications. Am. J. Cardiol. 92, 42J–49J (2003).

    Article  CAS  PubMed  Google Scholar 

  • Jia, L., Betters, J.L. & Yu, L. Niemann-pick C1-like 1 (NPC1L1) protein in intestinal and hepatic cholesterol transport. Annu. Rev. Physiol. 73, 239–259 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schwarz, M., Russell, D.W., Dietschy, J.M. & Turley, S.D. Marked reduction in bile acid synthesis in cholesterol 7α-hydroxylase-deficient mice does not lead to diminished tissue cholesterol turnover or to hypercholesterolemia. J. Lipid Res. 39, 1833–1843 (1998).

    CAS  PubMed  Google Scholar 

  • Repa, J.J. et al. Disruption of the sterol 27-hydroxylase gene in mice results in hepatomegaly and hypertriglyceridemia. Reversal by cholic acid feeding. J. Biol. Chem. 275, 39685–39692 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Gulewitsch, W. & Krimberg, R. Zur Kenntnis der Extrakivstoffe der Muskein, II. Mitteilung. Uber das Carnitin. Hoppe-Seyler's Z. Physiol. Chem. 45, 326–330 (1905).

    Article  CAS  Google Scholar 

  • Rebouche, C.J., Mack, D.L. & Edmonson, P.F. l-Carnitine dissimilation in the gastrointestinal tract of the rat. Biochemistry 23, 6422–6426 (1984).

    Article  CAS  PubMed  Google Scholar 

  • Rebouche, C.J. & Chenard, C.A. Metabolic fate of dietary carnitine in human adults: identification and quantification of urinary and fecal metabolites. J. Nutr. 121, 539–546 (1991).

    Article  CAS  PubMed  Google Scholar 

  • Zhang, A.Q., Mitchell, S.C. & Smith, R.L. Dietary precursors of trimethylamine in man: a pilot study. Food Chem. Toxicol. 37, 515–520 (1999).

    Article  CAS  PubMed  Google Scholar 

  • Delany, J.P., Snook, J.T., Vivian, V.M. & Cashmere, K. Metabolic effects of a carnitine-free diet fed to college students. Fed. Proc. 45, 815 (1986).

    Google Scholar 

  • Zeisel, S.H., Mar, M.H., Howe, J.C. & Holden, J.M. Concentrations of choline-containing compounds and betaine in common foods. J. Nutr. 133, 1302–1307 (2003).

    Article  CAS  PubMed  Google Scholar 

  • Fraser, G.E. Vegetarian diets: what do we know of their effects on common chronic diseases? Am. J. Clin. Nutr. 89, 1607S–1612S (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Key, T.J. et al. Mortality in vegetarians and nonvegetarians: detailed findings from a collaborative analysis of 5 prospective studies. Am. J. Clin. Nutr. 70, 516S–524S (1999).

    Article  CAS  PubMed  Google Scholar 

  • Estruch, R. et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N. Engl. J. Med. published online, http://dx.doi.org/10.1056/NEJMoa1200303 (25 February 2013).

  • Brown, M.S. & Goldstein, J.L. Expression of the familial hypercholesterolemia gene in heterozygotes: mechanism for a dominant disorder in man. Science 185, 61–63 (1974).

    Article  CAS  PubMed  Google Scholar 

  • Charach, G., Rabinovich, A., Argov, O., Weintraub, M. & Rabinovich, P. The role of bile Acid excretion in atherosclerotic coronary artery disease. Int. J. Vasc. Med. 2012, 949672 (2012).

    PubMed  Google Scholar 

  • Charach, G. et al. Decreased fecal bile acid output in patients with coronary atherosclerosis. J. Med. 29, 125–136 (1998).

    CAS  PubMed  Google Scholar 

  • Lu, Y., Feskens, E.J., Boer, J.M. & Muller, M. The potential influence of genetic variants in genes along bile acid and bile metabolic pathway on blood cholesterol levels in the population. Atherosclerosis 210, 14–27 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Miyake, J.H. et al. Transgenic expression of cholesterol-7-α-hydroxylase prevents atherosclerosis in C57BL/6J mice. Arterioscler. Thromb. Vasc. Biol. 22, 121–126 (2002).

    Article  CAS  PubMed  Google Scholar 

  • Post, S.M., de Crom, R., van Haperen, R., van Tol, A. & Princen, H.M. Increased fecal bile acid excretion in transgenic mice with elevated expression of human phospholipid transfer protein. Arterioscler. Thromb. Vasc. Biol. 23, 892–897 (2003).

    Article  CAS  PubMed  Google Scholar 

  • Zong, C. et al. Chitosan oligosaccharides promote reverse cholesterol transport and expression of scavenger receptor BI and CYP7A1 in mice. Exp. Biol. Med. (Maywood) 237, 194–200 (2012).

    Article  CAS  Google Scholar 

  • Altmann, S.W. et al. Niemann-Pick C1 like 1 protein is critical for intestinal cholesterol absorption. Science 303, 1201–1204 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Liberles, S.D. & Buck, L.B. A second class of chemosensory receptors in the olfactory epithelium. Nature 442, 645–650 (2006).

    Article  CAS  PubMed  Google Scholar 

  • Suska, A., Ibanez, A.B., Lundstrom, I. & Berghard, A. G protein–coupled receptor mediated trimethylamine sensing. Biosens. Bioelectron. 25, 715–720 (2009).

    Article  CAS  PubMed  Google Scholar 

  • Bai, C., Biwersi, J., Verkman, A.S. & Matthay, M.A. A mouse model to test the in vivo efficacy of chemical chaperones. J. Pharmacol. Toxicol. Methods 40, 39–45 (1998).

    Article  CAS  PubMed  Google Scholar 

  • Mello, C.C. & Barrick, D. Measuring the stability of partly folded proteins using TMAO. Protein Sci. 12, 1522–1529 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cordain, L. et al. Origins and evolution of the Western diet: health implications for the 21st century. Am. J. Clin. Nutr. 81, 341–354 (2005).

    Article  CAS  PubMed  Google Scholar 

  • Liszt, K. et al. Characterization of bacteria, clostridia and Bacteroides in faeces of vegetarians using qPCR and PCR-DGGE fingerprinting. Ann. Nutr. Metab. 54, 253–257 (2009).

    Article  CAS  PubMed  Google Scholar 

  • Elssner, T., Preusser, A., Wagner, U. & Kleber, H.P. Metabolism of l-carnitine by Enterobacteriaceae under aerobic conditions. FEMS Microbiol. Lett. 174, 295–301 (1999).

    Article  CAS  PubMed  Google Scholar 

  • Möller, B., Hippe, H. & Gottschalk, G. Degradation of various amine compounds by mesophilic clostridia. Arch. Microbiol. 145, 85–90 (1986).

    Article  PubMed  Google Scholar 

  • Eckburg, P.B. et al. Diversity of the human intestinal microbial flora. Science 308, 1635–1638 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  • Kleber, H.P. Bacterial carnitine metabolism. FEMS Microbiol. Lett. 147, 1–9 (1997).

    Article  CAS  PubMed  Google Scholar 

  • Hedayati, S.S. Dialysis-related carnitine disorder. Semin. Dial. 19, 323–328 (2006).

    Article  PubMed  Google Scholar 

  • Mingorance, C., Rodriguez-Rodriguez, R., Justo, M.L., Alvarez de Sotomayor, M. & Herrera, M.D. Critical update for the clinical use of l-carnitine analogs in cardiometabolic disorders. Vasc. Health Risk Manag. 7, 169–176 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  • The ARIC investigators. The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. Am. J. Epidemiol. 129, 687–702 (1989).

  • Chen, J. et al. Powerful statistical analysis for associating microbiomes to enviromental covariates using generalized Unifrac distances. Bioinformatics 28, 2106–2113 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Willems, G., Pison, G., Rousseeuw, P.J. & Van Aelst, S. A robust Hotelling test. Metrika 55, 125–138 (2002).

    Article  Google Scholar