J Philip Karl1, Xueyan Fu2, Xiaoxin Wang3, Yufeng Zhao3, Jian Shen3, Chenhong Zhang3, Benjamin E Wolfe4, Edward Saltzman5, Liping Zhao6, Sarah L Booth7. 1. Vitamin K Laboratory and Energy Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA; 2. Vitamin K Laboratory and. 3. State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China; 4. Department of Biology, Tufts University, Medford, MA. 5. Energy Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA; 6. State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China; Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China; and sarah.booth@tufts.edu lpzhao@sjtu.edu.cn. 7. Vitamin K Laboratory and sarah.booth@tufts.edu lpzhao@sjtu.edu.cn.
Abstract
BACKGROUND: Emerging evidence supports novel roles for vitamin K in cardiometabolic health, some of which may be unique to the bacterially synthesized vitamin K forms known as menaquinones. However, factors influencing menaquinone biosynthesis by the gut microbiota and associations with cardiometabolic health have not been examined. OBJECTIVE: The objective of this study was to identify associations between fecal menaquinone profiles, gut microbiota composition, and biomarkers of cardiometabolic health. DESIGN: The menaquinone profile and gut microbiota structure were periodically measured in fecal samples collected from 77 overweight Chinese adults who consumed a prescribed diet previously shown to alter gut microbiota composition and to improve cardiometabolic biomarkers. RESULTS: Covariance among menaquinones within individual fecal samples partitioned individuals into 2 distinct groups, herein introduced as menaquinotypes of the human gut. Menaquinotypes were characterized by differences in menaquinone (MK) 5 and MK9-MK13 and differences in the relative abundance of several operational taxonomic units (OTUs) delineated at the species level, predominantly within the genera Prevotella spp. and Bacteroides spp. Fecal MK4, MK6, and MK8 decreased during the intervention (P < 0.05); and longitudinal changes in the relative abundance of >100 OTUs were associated with altered fecal content of ≥1 individual menaquinone. The strongest and most consistent relations were between Prevotella spp. and MK5 and MK11-MK13, between Bacteroides spp. and MK9 and MK10, and between Escherichia/Shigella spp. and MK8. Neither individual menaquinones nor menaquinotypes were longitudinally associated with markers of glycemia, insulin resistance, or inflammation. CONCLUSIONS: These findings suggest that variability in fecal menaquinone content is predominantly determined by relatively few genera within the gut microbiota and that diet-mediated alterations in gut microbiota composition may provide a feasible approach for altering gut menaquinone content. This trial was registered at the Chinese Clinical Trials Registry as ChiCTR-TRC-09000353.
BACKGROUND: Emerging evidence supports novel roles for vitamin K in cardiometabolic health, some of which may be unique to the bacterially synthesized vitamin K forms known as menaquinones. However, factors influencing menaquinone biosynthesis by the gut microbiota and associations with cardiometabolic health have not been examined. OBJECTIVE: The objective of this study was to identify associations between fecal menaquinone profiles, gut microbiota composition, and biomarkers of cardiometabolic health. DESIGN: The menaquinone profile and gut microbiota structure were periodically measured in fecal samples collected from 77 overweight Chinese adults who consumed a prescribed diet previously shown to alter gut microbiota composition and to improve cardiometabolic biomarkers. RESULTS: Covariance among menaquinones within individual fecal samples partitioned individuals into 2 distinct groups, herein introduced as menaquinotypes of the human gut. Menaquinotypes were characterized by differences in menaquinone (MK) 5 and MK9-MK13 and differences in the relative abundance of several operational taxonomic units (OTUs) delineated at the species level, predominantly within the genera Prevotella spp. and Bacteroides spp. Fecal MK4, MK6, and MK8 decreased during the intervention (P < 0.05); and longitudinal changes in the relative abundance of >100 OTUs were associated with altered fecal content of ≥1 individual menaquinone. The strongest and most consistent relations were between Prevotella spp. and MK5 and MK11-MK13, between Bacteroides spp. and MK9 and MK10, and between Escherichia/Shigella spp. and MK8. Neither individual menaquinones nor menaquinotypes were longitudinally associated with markers of glycemia, insulin resistance, or inflammation. CONCLUSIONS: These findings suggest that variability in fecal menaquinone content is predominantly determined by relatively few genera within the gut microbiota and that diet-mediated alterations in gut microbiota composition may provide a feasible approach for altering gut menaquinone content. This trial was registered at the Chinese Clinical Trials Registry as ChiCTR-TRC-09000353.
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