The influence of maternal malnutrition on folate and inositol production and transport in the placenta and gut − a mechanism for fetal growth restriction and fetal disorders?
Maternal malnutrition and micronutrient deficiencies can alter fetal development. However, the mechanisms underlying these relationships are poorly understood. A systems-approach was used to investigate the effects of malnutrition 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. 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 abundance of three lactobacilli taxa were higher in HF vs. UN and CON. HF-fed mothers had higher gut Pcft and Rfc1 , and lower Smit2 , mRNA expression vs. UN and CON. HF placentae had increased Fr β expression vs. UN. mRNA expression of Pcft , 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 select gut microbes and folate/inositol transporters, which may influence maternal micronutrient status and delivery to the fetus, impacting pregnancy and fetal outcomes.