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 β-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.

中文翻译：

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血清神经酰胺升高与肥胖相关的肠道菌群失调和葡萄糖代谢受损有关。


简介 肠道微生物丰富度低与血脂异常和胰岛素抵抗有关，神经酰胺和其他鞘脂与糖尿病的发生有关。目的 确定循环鞘脂（特别是神经酰胺）是否与糖尿病风险增加的肥胖患者肠道微生物组的改变有关。方法 这是对饮食/减肥干预措施的横断面和纵向回顾性分析。从 49 名参与者（41 名女性）收集禁食血清，并通过 HPLC-MS/MS 进行分析，以量化 45 种鞘脂。对粪便进行鸟枪法宏基因组测序，以分析肠道微生物组。结果 血清神经酰胺与空腹血糖呈正相关，但与空腹和 OGTT 衍生的胰岛素敏感性和 β 细胞功能指标呈负相关，这证实了与葡萄糖稳态恶化的联系。已证明与肠道菌群失调存在显着相关性，其中 SM 和神经酰胺与基因丰富度呈负相关。脂肪酸链长度为 20-24 个碳的神经酰胺与低丰富度最相关。饮食引起的体重减轻提高了基因丰富度，减少了大多数鞘脂。 31 种 MGS 与神经酰胺呈负相关，其中大部分对应于未鉴定的细菌种类，其中包括许多双歧杆菌和史密斯甲烷短杆菌。较高的神经酰胺水平还与脂多糖合成和鞭毛素合成（两种病原体相关分子模式）宏基因组模块的增加以及涉及产甲烷和胆汁酸代谢的基因富集度的减少有关。 结论 这项研究确定了超重/肥胖人群肠道微生物群丰富度、神经酰胺和糖尿病风险之间的关联，并表明肠道微生物群可能导致代谢紊乱中脂质代谢失调。