Elevated serum ceramides are linked with obesity-associated gut dysbiosis and impaired glucose metabolism.
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ABSTRACT: INTRODUCTION:Low gut microbiome richness is associated with dyslipidemia and insulin resistance, and ceramides and other sphingolipids are implicated in the development of diabetes. OBJECTIVES:Determine whether circulating sphingolipids, particularly ceramides, are associated with alterations in the gut microbiome among obese patients with increased diabetes risk. METHODS:This was a cross-sectional and longitudinal retrospective analysis of a dietary/weight loss intervention. Fasted serum was collected from 49 participants (41 women) and analyzed by HPLC-MS/MS to quantify 45 sphingolipids. Shotgun metagenomic sequencing of stool was performed to profile the gut microbiome. RESULTS:Confirming the link to deteriorated glucose homeostasis, serum ceramides were positively correlated with fasting glucose, but inversely correlated with fasting and OGTT-derived measures of insulin sensitivity and ?-cell function. Significant associations with gut dysbiosis were demonstrated, with SM and ceramides being inversely correlated with gene richness. Ceramides with fatty acid chain lengths of 20-24 carbons were the most associated with low richness. Diet-induced weight loss, which improved gene richness, decreased most sphingolipids. Thirty-one MGS, mostly corresponding to unidentified bacteria species, were inversely correlated with ceramides, including a number of Bifidobacterium and Methanobrevibacter smithii. Higher ceramide levels were also associated with increased metagenomic modules for lipopolysaccharide synthesis and flagellan synthesis, two pathogen-associated molecular patterns, and decreased enrichment of genes involved in methanogenesis and bile acid metabolism. CONCLUSION:This study identifies an association between gut microbiota richness, ceramides, and diabetes risk in overweight/obese humans, and suggests that the gut microbiota may contribute to dysregulation of lipid metabolism in metabolic disorders.
SUBMITTER: Kayser BD
PROVIDER: S-EPMC7165363 | biostudies-literature | 2019 Oct
REPOSITORIES: biostudies-literature
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