Maternal gut microbiota Bifidobacterium promotes placental morphogenesis, nutrient transport and fetal growth in mice

Abstract

The gut microbiota plays a central role in regulating host metabolism. While substantial progress has been made in discerning how the microbiota influences host functions post birth and beyond, little is known about how key members of the maternal gut microbiota can influence feto-placental growth. Notably, in pregnant women, Bifidobacterium represents a key beneficial microbiota genus, with levels observed to increase across pregnancy. Here, using germ-free and specific-pathogen-free mice, we demonstrate that the bacterium Bifidobacterium breve UCC2003 modulates maternal body adaptations, placental structure and nutrient transporter capacity, with implications for fetal metabolism and growth. Maternal and placental metabolome were affected by maternal gut microbiota (i.e. acetate, formate and carnitine). Histological analysis of the placenta confirmed that Bifidobacterium modifies placental structure via changes in Igf2P0, Dlk1, Mapk1 and Mapk14 expression. Additionally, B. breve UCC2003, acting through Slc2a1 and Fatp1-4 transporters, was shown to restore fetal glycaemia and fetal growth in association with changes in the fetal hepatic transcriptome. Our work emphasizes the importance of the maternal gut microbiota on feto-placental development and sets a foundation for future research towards the use of probiotics during pregnancy.

Gut bacterial species in late trimester of pregnant sows influence the occurrence of stillborn piglet through pro-inflammation response

“…Maternal gut microbiota could affect maternal and placental metabolome (i.e. acetate, formate and carnitine), and then promote placental morphogenesis, nutrient transport and fetal growth in mice ( 18 ). We indeed observed that normal sows had significantly higher concentration of SCFAs in feces than sows giving birth to stillborn piglets.…”

“…In mice, intake of high-fat diet could result in placental hypoxia which impaired the development of the fetus ( 17 ). Bifidobacterium in maternal gut microbiota promotes placental morphogenesis, nutrient transport and fetal growth in mice ( 18 ). By far, whether the alteration of gut microbiota causes the occurrence of stillborn piglets in sows has still unknown.…”

Maternal and intrauterine influences on feto-placental growth are accompanied by sexually dimorphic changes in placental mitochondrial respiration, and metabolic signalling pathways

“…Protein abundance was determined in placental LZ samples (representative for each sex and genotype) using western blotting as previously described [1,34]. Briefly, proteins were extracted using RIPA buffer (Thermo Fisher Scientific, USA) supplemented with Mini EDTA-free protease inhibitor cocktail mix (Roche, CH).…”

Microbiome-based interventions to modulate gut ecology and the immune system

“…Immune priming begins in utero with the mother and can be linked to increased Bifidobacterium over the course of pregnancy. Supplementation of germ-free dams with Bifidobacterium breve UCC2003 is associated with transcriptional and morphological changes in the placenta and foetal compartments, including alterations of foetal liver immune pathways 208 . Other studies in humans have also indicated that maternal diet, such as fibre, and microbiome shape immune factors in cord blood, being associated with cord blood IgA 209 .…”