Plasma high-resolution metabolomics identifies linoleic acid and linked metabolic pathways associated with bone mineral density.
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.
['Bellissimo|Moriah P|MP|', 'Ziegler|Thomas R|TR|', 'Jones|Dean P|DP|', 'Liu|Ken H|KH|', 'Fernandes|Jolyn|J|', 'Roberts|Joseph L|JL|', 'Weitzmann|M Neale|MN|', 'Pacifici|Roberto|R|', 'Alvarez|Jessica A|JA|']
D015502:Absorptiometry, Photon D000328:Adult D015415:Biomarkers D015519:Bone Density D002853:Chromatography, Liquid D003430:Cross-Sectional Studies D005260:Female D006801:Humans D016014:Linear Models D019787:Linoleic Acid D008159:Lumbar Vertebrae D008297:Male D013058:Mass Spectrometry D053858:Metabolic Networks and Pathways D055432:Metabolomics D008875:Middle Aged D011453:Prostaglandins D018570:Risk Assessment
Nutrition Fats Inflammation Omega-6 PUFA Skeletal health