Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington, United States of America.
Department of Medicinal Chemistry, School of Pharmacy, University of Washington, Seattle, Washington, United States of America.
PLoS One. 2021 Mar 12;16(3):e0248351. doi: 10.1371/journal.pone.0248351. eCollection 2021.
Pregnancy is associated with metabolic changes to accommodate the mother and her growing fetus. The microbiome has been shown to modulate host metabolism of endogenous and exogenous substances. However, the combined effects of pregnancy and the microbiome on host metabolism have not been investigated. The objective of this study was to investigate how the microbiome affects overall hepatic metabolic processes during pregnancy. We assessed these changes within 4 groups of C57BL/6 mice: conventional non-pregnant, conventional pregnant, germ-free non-pregnant, and germ-free pregnant mice. We performed RNA-seq analysis on liver tissues and LC-MS/MS analysis of the plasma to assess the effects of pregnancy and the microbiome on hepatic transcriptome and untargeted plasma metabolome to describe metabolic changes as results of both pregnancy and lack of microbiome. By integrating transcriptomics and metabolomics data, we identified eight metabolic pathways that were significantly enriched for differentially expressed genes associated with pregnancy in both conventional and germ-free mice. Notably, of the eight pathways, 4 pathways (retinol metabolism, arachidonic acid metabolism, linoleic acid metabolism, and steroid hormone biosynthesis) which are all critical for normal pregnancy and fetal development were affected by the germ-free status in pregnant mice, but not at all in non-pregnant mice, indicating that the alterations in these four pathways caused by the lack of microbiome are unique for pregnancy. These results provide novel insight into the role of the microbiome in modulating host metabolic processes critical for maternal health and fetal development during pregnancy.
妊娠与代谢变化有关，以适应母亲及其不断成长的胎儿。微生物组已被证明可以调节宿主内源性和外源性物质的代谢。然而，妊娠和微生物组对宿主代谢的综合影响尚未得到研究。本研究的目的是研究微生物组如何在妊娠期间影响整体肝脏代谢过程。我们评估了 4 组 C57BL/6 小鼠的变化：常规未妊娠、常规妊娠、无菌未妊娠和无菌妊娠小鼠。我们对肝组织进行 RNA-seq 分析，并对血浆进行 LC-MS/MS 分析，以评估妊娠和微生物组对肝转录组和非靶向血浆代谢组的影响，以描述妊娠和缺乏微生物组的代谢变化。通过整合转录组学和代谢组学数据，我们确定了 8 条代谢途径，这些途径在常规和无菌小鼠的妊娠相关差异表达基因中显著富集。值得注意的是，在这 8 条途径中，4 条途径（视黄醇代谢、花生四烯酸代谢、亚油酸代谢和类固醇激素生物合成）对正常妊娠和胎儿发育至关重要，这些途径在妊娠无菌小鼠中受到影响，但在非妊娠小鼠中根本不受影响，这表明由于缺乏微生物组而导致的这四条途径的改变是妊娠所特有的。这些结果为微生物组在调节宿主代谢过程中的作用提供了新的见解，这些代谢过程对妊娠期间母婴健康和胎儿发育至关重要。
