Microbiome and multiomics of the developing intestine: Nutritional and environmental perturbations

Antenatal origins of the perinatal microbiome

The development of the neonatal microbiome, immunity, and metabolic homeostasis may be influenced by antenatal factors such as maternal modifiers or maternal determinants. ^, Maternal microbial colonization has been shown to affect neonatal microbial colonization and development of neonatal immunity. Animal studies have demonstrated the effects of maternal microbiota on infants’ transcription profiles, including those involved in innate immunity (antibacterial peptides), inflammation, and metabolism of microbial molecules. Maternal Immunoglobulin A (IgA) in breast milk binds to infant intestinal bacteria (especially Enterobacteriaceae , a family of bacteria under the phylum Proteobacteria ) and may play a protective role against necrotizing enterocolitis (NEC). Maternal obesity and a high-fat diet during pregnancy may have an effect on the neonate’s immune system, affect neonatal microbial colonization, and predispose the neonate to metabolic disease later in life. The hypothesized mechanisms for this effect may be that the maternal metabolic derangement affects the infant’s liver and other end organs through altered metabolite production, altered gut barrier integrity, and hematopoietic immune cells. Maternal programming of the fetal immune system may be effected by maternal antibodies, inflammatory mediators, micronutrients, microbial products, and maternal cells.

Prior to birth, the maternal and fetal ecosystems may play a role in the timing of delivery. Specific microbiome communities or specific organisms that predispose to preterm births have not been identified. However, perturbations of the maternal microbiome, including the vaginal, gastrointestinal, amniotic fluid, and placental microbiomes, have been reported in preterm birth. Inflammation and the presence of microbial DNA (or microbiome) in the amniotic fluid have been associated with preterm delivery. The presence of a placental microbiome or intrauterine microbiome in normal pregnancies not complicated by chorioamnionitis or preterm rupture of membranes is a matter of debate. Aagaard and colleagues, in a population-based cohort of placental specimens collected under sterile conditions from 320 subjects, reported a unique placental microbiome niche composed of nonpathogenic commensal microbiota from the Firmicutes , Tenericutes , Proteobacteria , Bacteroidetes , and Fusobacteria phyla. In aggregate, the placental microbiome profiles were most like the maternal oral microbiome. The placental microbiome was associated with a remote history of antenatal infection such as urinary tract infection in the first trimester, as well as with preterm birth. Other investigators have questioned the presence of the placental microbiome in normal pregnancies and attributed results to environmental contamination of samples. Analyses of microbiota from first-pass meconium indicate the possibility of in utero colonization of the fetal gastrointestinal system. ^{, ,} Intrapartum antibiotic prophylaxis causes perturbations in the infant gut microbiome in both vaginal and caesarean section deliveries that may last up to a year, especially in those who are not breastfed.