Moriah P Bellissimo1, Thomas R Ziegler2, Dean P Jones3, Ken H Liu4, Jolyn Fernandes5, Joseph L Roberts6, M Neale Weitzmann7, Roberto Pacifici8, Jessica A Alvarez9. 1. Nutrition and Health Sciences Doctoral Program, Laney Graduate School, Emory University, Atlanta, GA, USA; Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; Emory Center for Clinical and Molecular Nutrition, Emory University, Atlanta, GA, USA. 2. Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; Emory Center for Clinical and Molecular Nutrition, Emory University, Atlanta, GA, USA; Atlanta Department of Veterans Affairs Medical Center, Decatur, GA, USA; Emory Microbiome Research Center, Emory University, Atlanta, GA, USA. Electronic address: tzieg01@emory.edu. 3. Emory Center for Clinical and Molecular Nutrition, Emory University, Atlanta, GA, USA; Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA. 4. Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA. 5. Department of Pediatrics, Section of Neonatal-Perinatal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. 6. Nutrition and Health Sciences Doctoral Program, Laney Graduate School, Emory University, Atlanta, GA, USA; Department of Orthopaedics, Emory University School of Medicine, Atlanta, GA, USA. 7. Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; Atlanta Department of Veterans Affairs Medical Center, Decatur, GA, USA; Emory Microbiome Research Center, Emory University, Atlanta, GA, USA. 8. Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; Emory Microbiome Research Center, Emory University, Atlanta, GA, USA; Immunology and Molecular Pathogenesis Program, Emory University, Atlanta, GA, USA. 9. Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; Emory Center for Clinical and Molecular Nutrition, Emory University, Atlanta, GA, USA; Emory Microbiome Research Center, Emory University, Atlanta, GA, USA. Electronic address: jessica.alvarez@emory.edu.
Abstract
BACKGROUND & AIMS: There is a considerable degree of variation in bone mineral density (BMD) within populations. Use of plasma metabolomics may provide insight into established and novel determinants of BMD variance, such as nutrition and gut microbiome composition, to inform future prevention and treatment strategies for loss of BMD. Using high-resolution metabolomics (HRM), we examined low-molecular weight plasma metabolites and nutrition-related metabolic pathways associated with BMD. METHODS: This cross-sectional study included 179 adults (mean age 49.5 ± 10.3 yr, 64% female). Fasting plasma was analyzed using ultra-high-resolution mass spectrometry with liquid chromatography. Whole body and spine BMD were assessed by dual energy X-ray absorptiometry and expressed as BMD (g/cm2) or Z-scores. Multiple linear regression, pathway enrichment, and module analyses were used to determine key plasma metabolic features associated with bone density. RESULTS: Of 10,210 total detected metabolic features, whole body BMD Z-score was associated with 710 metabolites, which were significantly enriched in seven metabolic pathways, including linoleic acid, fatty acid activation and biosynthesis, and glycerophospholipid metabolism. Spine BMD was associated with 970 metabolites, significantly enriched in pro-inflammatory pathways involved in prostaglandin formation and linoleic acid metabolism. In module analyses, tryptophan- and polyamine-derived metabolites formed a network that was significantly associated with spine BMD, supporting a link with the gut microbiome. CONCLUSIONS: Plasma HRM provides comprehensive information relevant to nutrition and components of the microbiome that influence bone health. This data supports pro-inflammatory fatty acids and the gut microbiome as novel regulators of postnatal bone remodeling.
BACKGROUND & AIMS: There is a considerable degree of variation in bone mineral density (BMD) within populations. Use of plasma metabolomics may provide insight into established and novel determinants of BMD variance, such as nutrition and gut microbiome composition, to inform future prevention and treatment strategies for loss of BMD. Using high-resolution metabolomics (HRM), we examined low-molecular weight plasma metabolites and nutrition-related metabolic pathways associated with BMD. METHODS: This cross-sectional study included 179 adults (mean age 49.5 ± 10.3 yr, 64% female). Fasting plasma was analyzed using ultra-high-resolution mass spectrometry with liquid chromatography. Whole body and spine BMD were assessed by dual energy X-ray absorptiometry and expressed as BMD (g/cm2) or Z-scores. Multiple linear regression, pathway enrichment, and module analyses were used to determine key plasma metabolic features associated with bone density. RESULTS: Of 10,210 total detected metabolic features, whole body BMD Z-score was associated with 710 metabolites, which were significantly enriched in seven metabolic pathways, including linoleic acid, fatty acid activation and biosynthesis, and glycerophospholipid metabolism. Spine BMD was associated with 970 metabolites, significantly enriched in pro-inflammatory pathways involved in prostaglandin formation and linoleic acid metabolism. In module analyses, tryptophan- and polyamine-derived metabolites formed a network that was significantly associated with spine BMD, supporting a link with the gut microbiome. CONCLUSIONS: Plasma HRM provides comprehensive information relevant to nutrition and components of the microbiome that influence bone health. This data supports pro-inflammatory fatty acids and the gut microbiome as novel regulators of postnatal bone remodeling.
Authors: Moriah P Bellissimo; Qingpo Cai; Thomas R Ziegler; Ken H Liu; Phong H Tran; Miriam B Vos; Greg S Martin; Dean P Jones; Tianwei Yu; Jessica A Alvarez Journal: Obesity (Silver Spring) Date: 2019-11 Impact factor: 5.002
Authors: Claes Ohlsson; Cecilia Engdahl; Frida Fåk; Annica Andersson; Sara H Windahl; Helen H Farman; Sofia Movérare-Skrtic; Ulrika Islander; Klara Sjögren Journal: PLoS One Date: 2014-03-17 Impact factor: 3.240
Authors: Raúl Roncero-Martín; Ignacio Aliaga; Jose M Moran; Luis M Puerto-Parejo; Purificación Rey-Sánchez; María de la Luz Canal-Macías; Antonio Sánchez-Fernández; Juan D Pedrera-Zamorano; Fidel López-Espuela; Vicente Vera; Purificación Cerrato-Carretero; Jesús M Lavado-García Journal: Nutrients Date: 2021-04-25 Impact factor: 5.717
Authors: Moriah P Bellissimo; Joseph L Roberts; Dean P Jones; Ken H Liu; Kaitlin R Taibl; Karan Uppal; M Neale Weitzmann; Roberto Pacifici; Hicham Drissi; Thomas R Ziegler; Jessica A Alvarez Journal: Nutrients Date: 2020-10-16 Impact factor: 5.717