ω-3脂肪酸对2型糖尿病患者高甘油三酯血症、脂质组学和肠道微生物群的影响

Impact of omega-3 fatty acids on hypertriglyceridemia, lipidomics, and gut microbiome in patients with type 2 diabetes.

作者信息

Lu Jieli, Liu Ruixin, Ren Huahui, Wang Shuangyuan, Hu Chunyan, Shi Zhun, Li Mian, Liu Wei, Wan Qin, Su Qing, Li Qifu, Zheng Hongting, Qu Shen, Yang Fangming, Ji Hongyi, Lin Hong, Qi Hongyan, Wu Xueyan, Wu Kui, Chen Yuhong, Xu Yu, Xu Min, Wang Tiange, Zheng Jie, Ning Guang, Zheng Ruizhi, Bi Yufang, Zhong Huanzi, Wang Weiqing

机构信息

Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

BGI Research, Shenzhen, China; Institute of Intelligent Medical Research (IIMR), BGI Genomics, Shenzhen, China.

出版信息

Med. 2025 Jan 10;6(1):100496. doi: 10.1016/j.medj.2024.07.024. Epub 2024 Aug 19.

DOI:10.1016/j.medj.2024.07.024

PMID:39163858

Abstract

BACKGROUND

Fish oil (FO), a mixture of omega-3 fatty acids mainly comprising docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), has been recommended for patients with type 2 diabetes (T2D) and hypertriglyceridemia. However, its effects on lipidomic profiles and gut microbiota and the factors influencing triglyceride (TG) reduction remain unclear.

METHODS

We conducted a 12-week, randomized, double-blind, placebo-controlled trial in 309 Chinese patients with T2D with hypertriglyceridemia (ClinicalTrials.gov: NCT03120299). Participants were randomly assigned (1:1) to receive either 4 g FO or corn oil for 12 weeks. The primary outcome was changes in serum TGs and the lipidomic profile, and the secondary outcome included changes in the gut microbiome and other metabolic variables.

FINDINGS

The FO group had significantly better TG reduction (mean [95% confidence interval (CI)]: -1.51 [-2.01, -1.01] mmol/L) compared to the corn oil group (-0.66 [-1.15, -0.16] mmol/L, p = 0.02). FO significantly altered the serum lipid profile by reducing low-unsaturated TG species and increasing those containing DHA or EPA. FO had minor effects on gut microbiota, while baseline microbial features predicted the TG response to FO better than phenotypic or lipidomic features, potentially mediated by specific lipid metabolites. A total of 9 lipid metabolites significantly mediated the link between 4 baseline microbial variables and the TG response to FO supplementation.

CONCLUSIONS

Our findings demonstrate differential impacts of omega-3 fatty acids on lipidomic and microbial profiles in T2D and highlight the importance of baseline gut microbiota characteristics in predicting the TG-lowering efficacy of FO.

FUNDING

This study was funded by the National Nature Science Foundation.

摘要

背景

鱼油（FO）是一种主要由二十二碳六烯酸（DHA）和二十碳五烯酸（EPA）组成的ω-3脂肪酸混合物，已被推荐用于2型糖尿病（T2D）和高甘油三酯血症患者。然而，其对脂质组学特征和肠道微生物群的影响以及影响甘油三酯（TG）降低的因素仍不清楚。

方法

我们对309名患有T2D和高甘油三酯血症的中国患者进行了一项为期12周的随机、双盲、安慰剂对照试验（ClinicalTrials.gov：NCT03120299）。参与者被随机分配（1:1）接受4克FO或玉米油，为期12周。主要结局是血清TG和脂质组学特征的变化，次要结局包括肠道微生物群和其他代谢变量的变化。

研究结果

与玉米油组（-0.66 [-1.1, -0.16] mmol/L，p = 0.02）相比，FO组的TG降低效果显著更好（均值[95%置信区间（CI）]：-1.51 [-2.01, -1.01] mmol/L）。FO通过降低低不饱和TG种类并增加含有DHA或EPA的种类，显著改变了血清脂质特征。FO对肠道微生物群的影响较小，而基线微生物特征比表型或脂质组学特征更能预测TG对FO的反应，这可能由特定的脂质代谢物介导。共有9种脂质代谢物显著介导了4个基线微生物变量与TG对FO补充反应之间的联系。