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肠道微生物组在妊娠期间的生态变化及其向血脂异常的进展。

Ecological change of the gut microbiota during pregnancy and progression to dyslipidemia.

机构信息

State Key Laboratory of Reproductive Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.

Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.

出版信息

NPJ Biofilms Microbiomes. 2023 Apr 3;9(1):14. doi: 10.1038/s41522-023-00383-7.

Abstract

The composition of the gut microbiome was previously found to be associated with clinical responses to dyslipidemia, but there is limited consensus on the dynamic change of the gut microbiota during pregnancy and the specific microbiome characteristics linked to dyslipidemia in pregnant women. We collected fecal samples from 513 pregnant women at multiple time points during pregnancy in a prospective cohort. Taxonomic composition and functional annotations were determined by 16S rRNA amplicon sequencing and shotgun metagenomic sequencing. The predictive potential of gut microbiota on the risk of dyslipidemia was determined. The gut microbiome underwent dynamic changes during pregnancy, with significantly lower alpha diversity observed in dyslipidemic patients compared to their healthy counterparts. Several genera, including Bacteroides, Paraprevotella, Alistipes, Christensenellaceae R7 group, Clostridia UCG-014, and UCG-002 were negatively associated with lipid profiles and dyslipidemia. Further metagenomic analysis recognized a common set of pathways involved in gastrointestinal inflammation, where disease-specific microbes played an important role. Machine learning analysis confirmed the link between the microbiome and its progression to dyslipidemia, with a micro-averaged AUC of 0.824 (95% CI: 0.782-0.855) combined with blood biochemical data. Overall, the human gut microbiome, including Alistipes and Bacteroides, was associated with the lipid profile and maternal dyslipidemia during pregnancy by perturbing inflammatory functional pathways. Gut microbiota combined with blood biochemical data at the mid-pregnancy stage could predict the risk of dyslipidemia in late pregnancy. Therefore, the gut microbiota may represent a potential noninvasive diagnostic and therapeutic strategy for preventing dyslipidemia in pregnancy.

摘要

肠道微生物组的组成先前被发现与血脂异常的临床反应有关,但对于怀孕期间肠道微生物群的动态变化以及与孕妇血脂异常相关的特定微生物组特征,目前还没有达成共识。我们在一个前瞻性队列中,在怀孕期间的多个时间点收集了 513 名孕妇的粪便样本。通过 16S rRNA 扩增子测序和 shotgun 宏基因组测序来确定分类组成和功能注释。确定了肠道微生物群对血脂异常风险的预测潜力。肠道微生物组在怀孕期间发生动态变化,与健康对照组相比,血脂异常患者的 alpha 多样性显著降低。一些属,包括拟杆菌属、副拟杆菌属、Alistipes 属、Christensenellaceae R7 群、梭菌 UCG-014 和 UCG-002,与脂质谱和血脂异常呈负相关。进一步的宏基因组分析识别出一组共同涉及胃肠道炎症的途径,其中疾病特异性微生物发挥了重要作用。机器学习分析证实了微生物组与其向血脂异常进展之间的联系,结合血液生化数据,微生物平均 AUC 为 0.824(95%CI:0.782-0.855)。总的来说,人类肠道微生物组,包括 Alistipes 和 Bacteroides,通过扰乱炎症功能途径,与怀孕期间的脂质谱和母体血脂异常有关。在妊娠中期结合血液生化数据的肠道微生物组可以预测妊娠晚期血脂异常的风险。因此,肠道微生物组可能代表一种潜在的非侵入性诊断和治疗策略,用于预防妊娠期间的血脂异常。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d2b/10070613/22243ec789a6/41522_2023_383_Fig1_HTML.jpg

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