PT  - JOURNAL ARTICLE
AU  - Elia Palladino
AU  - Tim Van Mieghem
AU  - Kristin L. Connor
TI  - 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?
AID  - 10.1101/767012
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 767012
4099  - http://biorxiv.org/content/early/2020/02/25/767012.short
4100  - http://biorxiv.org/content/early/2020/02/25/767012.full
AB  - 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 Frβ 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 abundance of select gut microbes and folate/inositol transporters, which may influence maternal micronutrient status and delivery to the fetus, impacting pregnancy/fetal outcomes.