{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T18:29:47Z","timestamp":1793384987299,"version":"4.5.0"},"reference-count":65,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2018,10,12]]},"abstract":"<jats:sec>\n                    <jats:title>\n                      <jats:underline>Rationale:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      A strong association has emerged between the gut microbiome and atherosclerotic disease. Our recent data suggest\n                      <jats:italic>Lactobacillus<\/jats:italic>\n                      <jats:italic>plantarum<\/jats:italic>\n                      299v (Lp299v) supplementation reduces infarct size in male rats. Limited human data are available on the impact of Lp299v on the vasculature.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Objective:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>To determine whether oral Lp299v supplementation improves vascular endothelial function and reduces systemic inflammation in humans with stable coronary artery disease (CAD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Methods and Results:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      Twenty men with stable CAD consumed a drink containing Lp299v (20 billion CFU) once daily for 6 weeks. After a 4-week washout, subjects were given an option of additionally participating in a 10-day study of oral liquid vancomycin (250 mg QID). Vascular endothelial function was measured by brachial artery flow-mediated dilation. Before and after Lp299v, plasma short-chain fatty acids, trimethylamine oxide, and adipokine levels were measured. Additional plasma samples underwent unbiased metabolomic analyses using liquid chromatography\/mass spectroscopy. 16S rRNA sequencing was used to determine changes of the stool microbiome. Arterioles from patients with CAD were obtained, and endothelium-dependent vasodilation was measured by video microscopy after intraluminal incubation with plasma from Lp299v study subjects. Lp299v supplementation improved brachial flow-mediated dilation (\n                      <jats:italic>P<\/jats:italic>\n                      =0.008) without significant changes in plasma cholesterol profiles, fasting glucose, or body mass index. Vancomycin did not impact flow-mediated dilation. Lp299v supplementation decreased circulating levels of IL (interleukin)-8 (\n                      <jats:italic>P<\/jats:italic>\n                      =0.01), IL-12 (\n                      <jats:italic>P<\/jats:italic>\n                      =0.02), and leptin (\n                      <jats:italic>P<\/jats:italic>\n                      =0.0007) but did not significantly change plasma trimethylamine oxide concentrations (\n                      <jats:italic>P<\/jats:italic>\n                      =0.27). Plasma propionate (\n                      <jats:italic>P<\/jats:italic>\n                      =0.004) increased, whereas acetate levels decreased (\n                      <jats:italic>P<\/jats:italic>\n                      =0.03). Post-Lp299v plasma improved endothelium-dependent vasodilation in resistance arteries from patients with CAD (\n                      <jats:italic>P<\/jats:italic>\n                      =0.02).16S rRNA analysis showed the\n                      <jats:italic>Lactobacillus<\/jats:italic>\n                      genus was enriched in postprobiotic stool samples without other changes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Conclusions:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>Lp299v improved vascular endothelial function and decreased systemic inflammation in men with CAD, independent of changes in traditional risk factors and trimethylamine oxide. Circulating gut-derived metabolites likely account for these improvements and merit further study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Clinical Trial Registration:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.clinicaltrials.gov\">http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      . Unique identifier: NCT01952834.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.118.313565","type":"journal-article","created":{"date-parts":[[2018,10,11]],"date-time":"2018-10-11T14:00:56Z","timestamp":1539266456000},"page":"1091-1102","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":216,"title":["<i>Lactobacillus plantarum<\/i>\n                    299v Supplementation Improves Vascular Endothelial Function and Reduces Inflammatory Biomarkers in Men With Stable Coronary Artery Disease"],"prefix":"10.1161","volume":"123","author":[{"given":"Mobin","family":"Malik","sequence":"first","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Department of Medicine, Milwaukee, WI (M.M., T.M.S., S.T., J.W., R.Y., M.J.T., M.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tisha M.","family":"Suboc","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Department of Medicine, Milwaukee, WI (M.M., T.M.S., S.T., J.W., R.Y., M.J.T., M.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudhi","family":"Tyagi","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Department of Medicine, Milwaukee, WI (M.M., T.M.S., S.T., J.W., R.Y., M.J.T., M.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nita","family":"Salzman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (N.S.), Medical College of Wisconsin, Milwaukee."},{"name":"Department of Microbiology and Immunology (N.S.), Medical College of Wisconsin, Milwaukee."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingli","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Department of Medicine, Milwaukee, WI (M.M., T.M.S., S.T., J.W., R.Y., M.J.T., M.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Ying","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Department of Medicine, Milwaukee, WI (M.M., T.M.S., S.T., J.W., R.Y., M.J.T., M.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Tanner","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Department of Medicine, Milwaukee, WI (M.M., T.M.S., S.T., J.W., R.Y., M.J.T., M.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamatha","family":"Kakarla","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Department of Medicine, Milwaukee, WI (M.M., T.M.S., S.T., J.W., R.Y., M.J.T., M.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Baker","sequence":"additional","affiliation":[{"name":"Division of Congenital Cardiac Surgery, 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