233
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Intestinal microbiota metabolism of choline/phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). Herein we demonstrate that intestinal microbiota metabolism of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis. Omnivorous subjects are shown to produce significantly more TMAO than vegans/vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. Specific bacterial taxa in human feces are shown to associate with both plasma TMAO and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation ( n = 2,595) predict increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (MI, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice significantly altered cecal microbial composition, markedly enhanced synthesis of TMA/TMAO, and increased atherosclerosis, but not following suppression of intestinal microbiota. Dietary supplementation of TMAO, or either carnitine or choline in mice with intact intestinal microbiota, significantly reduced reverse cholesterol transport in vivo. Intestinal microbiota may thus participate in the well-established link between increased red meat consumption and CVD risk.

          Related collections

          Most cited references47

          • Record: found
          • Abstract: found
          • Article: not found

          Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis.

          Toll-like receptors (TLRs) play a crucial role in host defense against microbial infection. The microbial ligands recognized by TLRs are not unique to pathogens, however, and are produced by both pathogenic and commensal microorganisms. It is thought that an inflammatory response to commensal bacteria is avoided due to sequestration of microflora by surface epithelia. Here, we show that commensal bacteria are recognized by TLRs under normal steady-state conditions, and this interaction plays a crucial role in the maintenance of intestinal epithelial homeostasis. Furthermore, we find that activation of TLRs by commensal microflora is critical for the protection against gut injury and associated mortality. These findings reveal a novel function of TLRs-control of intestinal epithelial homeostasis and protection from injury-and provide a new perspective on the evolution of host-microbial interactions.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease.

            A reduction in dietary saturated fat has generally been thought to improve cardiovascular health. The objective of this meta-analysis was to summarize the evidence related to the association of dietary saturated fat with risk of coronary heart disease (CHD), stroke, and cardiovascular disease (CVD; CHD inclusive of stroke) in prospective epidemiologic studies. Twenty-one studies identified by searching MEDLINE and EMBASE databases and secondary referencing qualified for inclusion in this study. A random-effects model was used to derive composite relative risk estimates for CHD, stroke, and CVD. During 5-23 y of follow-up of 347,747 subjects, 11,006 developed CHD or stroke. Intake of saturated fat was not associated with an increased risk of CHD, stroke, or CVD. The pooled relative risk estimates that compared extreme quantiles of saturated fat intake were 1.07 (95% CI: 0.96, 1.19; P = 0.22) for CHD, 0.81 (95% CI: 0.62, 1.05; P = 0.11) for stroke, and 1.00 (95% CI: 0.89, 1.11; P = 0.95) for CVD. Consideration of age, sex, and study quality did not change the results. A meta-analysis of prospective epidemiologic studies showed that there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD. More data are needed to elucidate whether CVD risks are likely to be influenced by the specific nutrients used to replace saturated fat.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Concentrations of choline-containing compounds and betaine in common foods.

              Choline is important for normal membrane function, acetylcholine synthesis and methyl group metabolism; the choline requirement for humans is 550 mg/d for men (Adequate Intake). Betaine, a choline derivative, is important because of its role in the donation of methyl groups to homocysteine to form methionine. In tissues and foods, there are multiple choline compounds that contribute to total choline concentration (choline, glycerophosphocholine, phosphocholine, phosphatidylcholine and sphingomyelin). In this study, we collected representative food samples and analyzed the choline concentration of 145 common foods using liquid chromatography-mass spectrometry. Foods with the highest total choline concentration (mg/100 g) were: beef liver (418), chicken liver (290), eggs (251), wheat germ (152), bacon (125), dried soybeans (116) and pork (103). The foods with the highest betaine concentration (mg/100 g) were: wheat bran (1339), wheat germ (1241), spinach (645), pretzels (237), shrimp (218) and wheat bread (201). A number of epidemiologic studies have examined the relationship between dietary folic acid and cancer or heart disease. It may be helpful to also consider choline intake as a confounding factor because folate and choline methyl donation can be interchangeable.
                Bookmark

                Author and article information

                Journal
                9502015
                8791
                Nat Med
                Nat. Med.
                Nature medicine
                1078-8956
                1546-170X
                14 March 2013
                07 April 2013
                May 2013
                01 November 2013
                : 19
                : 5
                : 576-585
                Affiliations
                [1 ]Department of Cellular & Molecular Medicine, Cleveland Clinic, Cleveland, Ohio 44195, USA
                [2 ]Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic, Cleveland, Ohio 44195, USA
                [3 ]Department of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles 90095, USA
                [4 ]Department of Mathematics, Cleveland State University, Cleveland, Ohio 44115, USA
                [5 ]Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio 44195, USA
                [6 ]Department of Microbiology, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA
                [7 ]Division of Gastroenterology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA
                [8 ]Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA
                [9 ]Department of Pathology, Section on Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
                [10 ]Children’s Hospital Oakland Research Institute, Oakland, CA 94609, USA
                Author notes
                Address for Correspondence: Stanley L. Hazen, MD PhD, Department of Cellular & Molecular Medicine, Cleveland Clinic, 9500 Euclid Avenue, NC-10, Cleveland, OH 44195, Phone: (216) 445-9763, Fax: (216) 636-0392, hazens@ 123456ccf.org
                Article
                NIHMS450760
                10.1038/nm.3145
                3650111
                23563705
                b73b4bcf-a890-4aca-a298-5cc2733aafe3

                Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

                Funding
                Funded by: National Center for Research Resources : NCRR
                Award ID: UL1 RR024989 || RR
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK
                Award ID: RC1 DK086472 || DK
                Funded by: National Heart, Lung, and Blood Institute : NHLBI
                Award ID: R01 HL103931 || HL
                Funded by: National Heart, Lung, and Blood Institute : NHLBI
                Award ID: R01 HL103866 || HL
                Funded by: National Heart, Lung, and Blood Institute : NHLBI
                Award ID: R00 HL096166 || HL
                Funded by: National Heart, Lung, and Blood Institute : NHLBI
                Award ID: P20 HL113452 || HL
                Funded by: National Heart, Lung, and Blood Institute : NHLBI
                Award ID: P01 HL098055 || HL
                Funded by: National Heart, Lung, and Blood Institute : NHLBI
                Award ID: P01 HL076491 || HL
                Funded by: National Heart, Lung, and Blood Institute : NHLBI
                Award ID: P01 HL030568 || HL
                Funded by: National Heart, Lung, and Blood Institute : NHLBI
                Award ID: P01 HL028481 || HL
                Categories
                Article

                Medicine
                Medicine

                Comments

                Comment on this article