Maternal Obesity and Gut Microbiota Are Associated with Fetal Brain Development

Abstract

Obesity in pregnancy induces metabolic syndrome, low-grade inflammation, altered endocrine factors, placental function, and the maternal gut microbiome. All these factors impact fetal growth and development, including brain development. The lipid metabolic transporters of the maternal-fetal-placental unit are dysregulated in obesity. Consequently, the transport of essential long-chain PUFAs for fetal brain development is disturbed. The mother's gut microbiota is vital in maintaining postnatal energy homeostasis and maternal-fetal immune competence. Obesity during pregnancy changes the gut microbiota, affecting fetal brain development. Obesity in pregnancy can induce placental and intrauterine inflammation and thus influence the neurodevelopmental outcomes of the offspring. Several epidemiological studies observed an association between maternal obesity and adverse neurodevelopment. This review discusses the effects of maternal obesity and gut microbiota on fetal neurodevelopment outcomes. In addition, the possible mechanisms of the impacts of obesity and gut microbiota on fetal brain development are discussed.

Keywords: brain development; fetal development; maternal obesity; microbiota; obesity; placenta; pregnancy.

Figure 1

Diverse adipokines, cytokines, FABP4 and metabolic stress in obese women may affect fetal brain development. In pregnancies complicated by obesity, these factors mediate crosstalk among different cell populations within adipose and travel to remote organs to regulate their function. The long-term neurodevelopmental programming is linked to inflammation and placental serotonin production and LCPUFAs supply. Red arrows indicate “upregulation” while black arrows indicate “downregulation.

Figure 2

Maternal gut microbiota is modulated by obesity, antibiotics and a high-fat diet. Gut dysbiosis can affect fetal brain development via different mechanisms. Since, at birth, the newborn is colonized by maternal and environmental microbiota, therefore maternal gut microbe also affects the neonatal gut microbe. The gut microbiota signal to the adult brain via the vagus nerve, bacterial metabolites, gut hormones, and immune signalling. More data has now emerged that these pathways are functional in the fetus and newborn. Red arrows indicate “upregulation” while black arrows indicate “downregulation.