Maternal influences on fetal microbial colonization and immune development

Abstract

While critical for normal development, the exact timing of establishment of the intestinal microbiome is unknown. For example, although preterm labor and birth have been associated with bacterial colonization of the amniotic cavity and fetal membranes for many years, the prevailing dogma of a sterile intrauterine environment during normal term pregnancies has been challenged more recently. While found to be a key contributor of evolution in the animal kingdom, maternal transmission of commensal bacteria may also constitute a critical process during healthy pregnancies in humans with yet unclear developmental importance. Metagenomic sequencing has elucidated a rich placental microbiome in normal term pregnancies likely providing important metabolic and immune contributions to the growing fetus. Conversely, an altered microbial composition during pregnancy may produce aberrant metabolites impairing fetal brain development and life-long neurological outcomes. Here we review the current understanding of microbial colonization at the feto-maternal interface and explain how normal gut colonization drives a balanced neonatal mucosal immune system, while dysbiosis contributes to aberrant immune function early in life and beyond. We discuss how maternal genetics, diet, medications, and probiotics inform the fetal microbiome in preparation for perinatal and postnatal bacterial colonization.

Figure 1

Maternal influences on fetal microbial colonization and immune development. Maternal-fetal transmission of microbes is an evolutionary preserved phenomenon in the animal kingdom and likely an important mechanism for the development of a balanced immune system in the human fetus (,–71). (a) Maternal-fetal bacterial transfer is poorly understood and multiple mechanisms have been proposed (,–44,72). (b) Fetal and maternal host immunogenetic factors play a role in assemblage of the fetal and neonatal microbiome. Specific genes of interest are listed in Table 1 and reviewed by Spor et al. (73). (c) Ascending infection and ensuing chorioamnionitis have a major impact on the uterine environment and subsequent fetal development, including the intestinal microbiome (5,24). (d) Delivery mode (–65) and diet (68,74) strongly influence early life microbial colonization. Other life events, especially introduction of antibiotics and solid food, are associated with major shifts in the microbiota composition (75). Despite taxonomic variation, the functionality of the newborn intestinal microbiota converges towards his/her mother’s microbiome, supporting the early and sustained role of the maternal environment on health (76).