Association of maternal gut microbial metabolites with gestational diabetes mellitus: evidence from an original case-control study, meta-analysis, and Mendelian randomization.

IF 3.6 3区 医学 Q2 NUTRITION & DIETETICS
Mengxin Yao, Yue Xiao, Yanqun Sun, Bing Zhang, Yaling Ding, Qiuping Ma, Fei Liang, Zhuoqiao Yang, Wenxin Ge, Songliang Liu, Lili Xin, Jieyun Yin, Xiaoyan Zhu
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Abstract

Background: The associations of gut microbial metabolites, such as trimethylamine N-oxide (TMAO), its precursors, and phenylacetylglutamine (PAGln), with the risk of gestational diabetes mellitus (GDM) remain unclear.

Methods: Serum samples of 201 women with GDM and 201 matched controls were collected and then targeted metabolomics was performed to examine the metabolites of interest. Multivariable conditional logistic regression was applied to investigate the relationship between metabolites and GDM. Meta-analysis was performed to combine our results and four similar articles searched from online databases, and Mendelian randomization (MR) analysis was eventually conducted to explore the causalities.

Results: In the case-control study, after dichotomization and comparing the higher versus the lower group, the adjusted odds ratio and 95% confidence interval of choline and L-carnitine with GDM were 2.124 (1.186-3.803) and 0.293 (0.134-0.638), respectively; but neutral relationships between TMAO, betaine, and PAGln with GDM were observed. The following meta-analysis consistently revealed that L-carnitine was negatively associated with GDM. However, MR analyses showed no evidence of causalities.

Conclusions: Maternal levels of L-carnitine were related to the risk of GDM in both the original case-control study and meta-analysis. However, we did not observe any genetic evidence to establish a causal relationship between this metabolite and GDM.

Abstract Image

母体肠道微生物代谢物与妊娠糖尿病的关系:来自原始病例对照研究、荟萃分析和孟德尔随机分析的证据。
背景:肠道微生物代谢物(如三甲胺 N-氧化物(TMAO)及其前体和苯乙酰谷氨酰胺(PAGln))与妊娠糖尿病(GDM)风险的关系仍不清楚:收集了 201 名 GDM 妇女和 201 名匹配对照者的血清样本,然后进行了靶向代谢组学研究,以检测感兴趣的代谢物。应用多变量条件逻辑回归研究代谢物与 GDM 之间的关系。结合我们的研究结果和从在线数据库中搜索到的四篇类似文章进行了元分析,并最终进行了孟德尔随机化(MR)分析以探讨因果关系:在病例对照研究中,胆碱和左旋肉碱与 GDM 的调整几率比和 95% 置信区间分别为 2.124 (1.186-3.803) 和 0.293 (0.134-0.638),而 TMAO、甜菜碱和 PAGln 与 GDM 的关系为中性。随后的荟萃分析一致显示,左旋肉碱与 GDM 呈负相关。然而,MR 分析并未显示出因果关系:结论:在最初的病例对照研究和荟萃分析中,母体的左旋肉碱水平与 GDM 风险有关。结论:在最初的病例对照研究和荟萃分析中,母体的左旋肉碱水平与 GDM 的风险有关,但我们没有观察到任何遗传学证据表明这种代谢物与 GDM 之间存在因果关系。
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来源期刊
CiteScore
10.60
自引率
2.10%
发文量
189
审稿时长
3-6 weeks
期刊介绍: The European Journal of Clinical Nutrition (EJCN) is an international, peer-reviewed journal covering all aspects of human and clinical nutrition. The journal welcomes original research, reviews, case reports and brief communications based on clinical, metabolic and epidemiological studies that describe methodologies, mechanisms, associations and benefits of nutritional interventions for clinical disease and health promotion. Topics of interest include but are not limited to: Nutrition and Health (including climate and ecological aspects) Metabolism & Metabolomics Genomics and personalized strategies in nutrition Nutrition during the early life cycle Health issues and nutrition in the elderly Phenotyping in clinical nutrition Nutrition in acute and chronic diseases The double burden of ''malnutrition'': Under-nutrition and Obesity Prevention of Non Communicable Diseases (NCD)
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