Carleton University (Health Sciences), Ottawa, Ontario, Canada.
Mount Sinai Hospital (Obstetrics and Gynaecology), Toronto, Ontario, Canada.
Reprod Sci. 2021 Feb;28(2):447-461. doi: 10.1007/s43032-020-00297-1. Epub 2020 Sep 4.
Maternal malnutrition and micronutrient deficiencies can alter fetal development. However, the mechanisms underlying these relationships are poorly understood. We used a systems physiology approach to investigate diet-induced effects on maternal gut microbes and folate/inositol transport in the maternal/fetal gut and placenta. Female mice were fed a control diet (CON) diet, undernourished (UN, restricted by 30% of CON intake) or a high-fat diet (HF, 60% kcals fat) during pregnancy to model normal pregnancy, fetal growth restriction or maternal metabolic dysfunction, respectively. At gestational day 18.5, we assessed circulating folate levels by microbiological assay, relative abundance of gut lactobacilli by G3PhyloChip™, and folate/inositol transporters in placenta and maternal/fetal gut by qPCR/immunohistochemistry. UN and HF-fed mothers had lower plasma folate concentrations vs. CON. Relative abundances of three lactobacilli taxa were higher in HF vs. UN and CON. HF-fed mothers had higher gut proton coupled folate transporter (Pcft) and reduced folate carrier 1 (Rfc1), and lower sodium myo-inositol co-transporter 2 (Smit2), mRNA expression vs. UN and CON. HF placentae had increased folate receptor beta (Frβ) expression vs. UN. mRNA expression of Pcft, folate receptor alpha (Frα), and Smit2 was higher in gut of HF fetuses vs. UN and CON. Transporter protein expression was not different between groups. Maternal malnutrition alters abundance of select gut microbes and folate/inositol transporters, which may influence maternal micronutrient status and delivery to the fetus, impacting pregnancy/fetal outcomes.
母体营养不良和微量营养素缺乏会改变胎儿的发育。然而，这些关系的潜在机制尚不清楚。我们使用系统生理学方法研究了饮食对母体肠道微生物和母体/胎儿肠道和胎盘中叶酸/肌醇转运的影响。在妊娠期间，雌性小鼠分别用对照饮食（CON）、低营养（UN，CON 摄入量的 30%限制）或高脂肪饮食（HF，60%卡路里脂肪）喂养，分别模拟正常妊娠、胎儿生长受限或母体代谢功能障碍。在妊娠第 18.5 天，我们通过微生物学分析评估循环叶酸水平，通过 G3PhyloChip™评估肠道乳杆菌的相对丰度，通过 qPCR/免疫组织化学评估胎盘和母体/胎儿肠道中的叶酸/肌醇转运体。与 CON 相比，UN 和 HF 喂养的母亲血浆叶酸浓度较低。HF 组三种乳杆菌的相对丰度高于 UN 和 CON。HF 喂养的母亲肠道质子偶联叶酸转运体（Pcft）和还原叶酸载体 1（Rfc1）升高，而钠肌醇共转运体 2（Smit2）降低，mRNA 表达低于 UN 和 CON。HF 胎盘与 UN 相比，叶酸受体β（Frβ）表达增加。与 UN 和 CON 相比，HF 胎儿肠道中 Pcft、叶酸受体α（Frα）和 Smit2 的 mRNA 表达更高。转运蛋白表达在各组之间没有差异。母体营养不良改变了肠道微生物和叶酸/肌醇转运体的丰度，这可能会影响母体微量营养素状况和向胎儿的传递，从而影响妊娠/胎儿结局。
