孕期循环中的亚油酸及其与肠道微生物群在妊娠期糖尿病中的相互作用。

Circulating linoleic acid and its interplay with gut microbiota during pregnancy for gestational diabetes mellitus.

作者信息

Qiu Jiahui, Hu Ping, Li Fan, Huang Yichao, Yang Yunhaonan, Sun Fengjiang, Wu Ping, Lai Yuwei, Wang Yi, He Xiangwang, Dong Yidan, Zhang Peiqi, Zhang Shanshan, Wu Nianwei, Wang Tianlei, Yang Shizhuo, Li Shuo, Yuan Jiaying, Liu Xiaojuan, Liu Gang, Hu Yayi, Wu Jason H Y, Chen Da, Pan An, Pan Xiong-Fei

机构信息

Center for Reproductive Medicine, Department of Obstetrics and Gynecology & Section of Epidemiology and Population Health, Ministry of Education Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.

Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

出版信息

BMC Med. 2025 Apr 28;23(1):245. doi: 10.1186/s12916-025-04061-7.

DOI:10.1186/s12916-025-04061-7

PMID:40289092

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12036143/

Abstract

BACKGROUND

Circulating linoleic acid (LA) levels have been reported to be associated with various metabolic outcomes. However, the role of LA and its interplay with gut microbiota in gestational diabetes mellitus (GDM) remains unclear. This study aimed to investigate the longitudinal association between circulating LA levels during pregnancy and the risk of GDM, and the potential role of gut microbiota.

METHODS

A nested case-control study was conducted within the ongoing Tongji-Huaxi-Shuangliu Birth Cohort in Chengdu, China. Blood and fecal samples were collected during early and middle pregnancy from 807 participants. GDM was diagnosed in middle pregnancy using the International Association of Diabetes and Pregnancy Study Groups criteria. Plasma LA levels were measured using gas chromatography-mass spectrometry, and gut microbiota was analyzed through 16S rRNA gene sequencing and shotgun metagenomic sequencing. A two-sample Mendelian randomization study was conducted using data from the IEU OpenGWAS database and the FinnGen consortium.

RESULTS

Elevated plasma LA levels were associated with a lower risk of GDM in both early (P for trend = 0.002) and middle pregnancy (P for trend = 0.02). Consistently, Mendelian randomization analysis revealed that each unit increase in LA was associated with a 16% reduction in GDM risk (odds ratio: 0.84, 95% confidence interval: 0.72, 0.95). In early pregnancy, higher plasma LA levels were correlated with higher adiponectin levels (P < 0.001) and lower levels of triglycerides (P < 0.001), HbA1c (P = 0.04), and C-peptide (P = 0.04). The LA-accociated microbiota mediated the relationship between LA and C-peptide (P = 0.01). Additionally, the inverse association between LA and GDM was modified by Bilophila (P for interaction = 0.03), with a stronger association observed in participants with lower Bilophila levels in early pregnancy. Metagenomic analyses further showed that the LA-associated pathway (D-galacturonate degradation I) and its key enzyme (EC 4.2.1.7) were associated with metabolic traits.

CONCLUSIONS

Our study provides evidence for an inverse causal association between plasma LA levels during pregnancy and GDM risk, which is both mediated and modified by gut microbiota.

摘要

背景

据报道，循环亚油酸（LA）水平与多种代谢结果相关。然而，LA及其与肠道微生物群在妊娠期糖尿病（GDM）中的相互作用仍不清楚。本研究旨在探讨孕期循环LA水平与GDM风险之间的纵向关联，以及肠道微生物群的潜在作用。

方法

在中国成都正在进行的同济-华西-双流出生队列中开展了一项巢式病例对照研究。在妊娠早期和中期收集了807名参与者的血液和粪便样本。在妊娠中期根据国际糖尿病与妊娠研究组协会标准诊断GDM。使用气相色谱-质谱法测量血浆LA水平，并通过16S rRNA基因测序和鸟枪法宏基因组测序分析肠道微生物群。利用IEU OpenGWAS数据库和芬兰基因组联盟的数据进行了两样本孟德尔随机化研究。

结果

在妊娠早期（趋势P=0.002）和中期（趋势P=0.02），血浆LA水平升高均与GDM风险降低相关。同样，孟德尔随机化分析显示，LA每增加一个单位，GDM风险降低16%（比值比：0.84，95%置信区间：0.72，0.95）。在妊娠早期，较高的血浆LA水平与较高的脂联素水平（P<0.001）以及较低的甘油三酯水平（P<0.001）、糖化血红蛋白（HbA1c）水平（P=0.04）和C肽水平（P=0.04）相关。与LA相关的微生物群介导了LA与C肽之间的关系（P=0.01）。此外，LA与GDM之间的负相关关系受到嗜胆菌属的影响（交互作用P=0.03），在妊娠早期嗜胆菌属水平较低的参与者中观察到更强的相关性。宏基因组分析进一步表明，与LA相关的途径（D-半乳糖醛酸降解I）及其关键酶（EC 4.2.1.7）与代谢特征相关。