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亚洲华裔和欧洲白种成年人中种族与血糖异常的多组学特征研究:TOFI_Asia研究4年随访的横断面分析

Investigating Multi-Omic Signatures of Ethnicity and Dysglycaemia in Asian Chinese and European Caucasian Adults: Cross-Sectional Analysis of the TOFI_Asia Study at 4-Year Follow-Up.

作者信息

Faraj Saif, Joblin-Mills Aidan, Sequeira-Bisson Ivana R, Leiu Kok Hong, Tung Tommy, Wallbank Jessica A, Fraser Karl, Miles-Chan Jennifer L, Poppitt Sally D, Taylor Michael W

机构信息

School of Biological Sciences, University of Auckland, Auckland 1010, New Zealand.

Human Nutrition Unit, University of Auckland, Auckland 1024, New Zealand.

出版信息

Metabolites. 2025 Aug 1;15(8):522. doi: 10.3390/metabo15080522.

Abstract

Type 2 diabetes (T2D) is a global health epidemic with rising prevalence within Asian populations, particularly amongst individuals with high visceral adiposity and ectopic organ fat, the so-called Thin-Outside, Fat-Inside phenotype. Metabolomic and microbiome shifts may herald T2D onset, presenting potential biomarkers and mechanistic insight into metabolic dysregulation. However, multi-omics datasets across ethnicities remain limited. We performed cross-sectional multi-omics analyses on 171 adults (99 Asian Chinese, 72 European Caucasian) from the New Zealand-based TOFI_Asia cohort at 4-years follow-up. Paired plasma and faecal samples were analysed using untargeted metabolomic profiling (polar/lipid fractions) and shotgun metagenomic sequencing, respectively. Sparse multi-block partial least squares regression and discriminant analysis (DIABLO) unveiled signatures associated with ethnicity, glycaemic status, and sex. Ethnicity-based DIABLO modelling achieved a balanced error rate of 0.22, correctly classifying 76.54% of test samples. Polar metabolites had the highest discriminatory power (AUC = 0.96), with trigonelline enriched in European Caucasians and carnitine in Asian Chinese. Lipid profiles highlighted ethnicity-specific signatures: Asian Chinese showed enrichment of polyunsaturated triglycerides (TG.16:0_18:2_22:6, TG.18:1_18:2_22:6) and ether-linked phospholipids, while European Caucasians exhibited higher levels of saturated species (TG.16:0_16:0_14:1, TG.15:0_15:0_17:1). The bacteria , and characterised Asian Chinese participants, while sp. and characterised European Caucasians. Cross-omic correlations highlighted negative correlations of with amino acids (r = -0.84 to -0.76), while and positively correlated with long-chain triglycerides (r = 0.55-0.62). : Ethnicity drove robust multi-omic differentiation, revealing distinctive metabolic and microbial profiles potentially underlying the differential T2D risk between Asian Chinese and European Caucasians.

摘要

2型糖尿病(T2D)是一种全球健康流行病,在亚洲人群中的患病率不断上升,尤其是在内脏脂肪过多和异位器官脂肪较多的个体中,即所谓的“外瘦内胖”表型。代谢组学和微生物组的变化可能预示着T2D的发病,为代谢失调提供潜在的生物标志物和机制见解。然而,不同种族的多组学数据集仍然有限。我们对来自新西兰的TOFI_Asia队列的171名成年人(99名华裔亚洲人、72名欧洲白种人)进行了为期4年随访的横断面多组学分析。分别使用非靶向代谢组学分析(极性/脂质部分)和鸟枪法宏基因组测序对配对的血浆和粪便样本进行分析。稀疏多块偏最小二乘回归和判别分析(DIABLO)揭示了与种族、血糖状态和性别的相关特征。基于种族的DIABLO模型实现了0.22的平衡错误率,正确分类了76.54%的测试样本。极性代谢物具有最高的鉴别力(AUC = 0.96),葫芦巴碱在欧洲白种人中富集,肉碱在华裔亚洲人中富集。脂质谱突出了种族特异性特征:华裔亚洲人显示多不饱和甘油三酯(TG.16:0_18:2_22:6,TG.18:1_18:2_22:6)和醚连接磷脂富集,而欧洲白种人则表现出较高水平的饱和物种(TG.16:0_16:0_14:1,TG.15:0_15:0_17:1)。[具体细菌名称]和[具体细菌名称]是华裔亚洲参与者的特征菌,而[具体细菌名称]和[具体细菌名称]是欧洲白种人的特征菌。跨组学相关性突出了[具体细菌名称]与氨基酸的负相关性(r = -0.84至-0.76),而[具体细菌名称]和[具体细菌名称]与长链甘油三酯呈正相关(r = 0.55 - 0.62)。结论:种族驱动了强大的多组学分化,揭示了华裔亚洲人和欧洲白种人之间T2D风险差异潜在的独特代谢和微生物特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5c2/12388023/f93a22741e02/metabolites-15-00522-g001.jpg

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