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
School of Biological Sciences, University of Auckland, Auckland 1010, New Zealand.
Human Nutrition Unit, University of Auckland, Auckland 1024, New Zealand.
Metabolites. 2025 Aug 1;15(8):522. doi: 10.3390/metabo15080522.
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.
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。
