Maternal microbiome's pivotal role in shaping fetal and neonatal immune systems during pregnancy

By Vijay Kumar MalesuReviewed by Benedette Cuffari, M.Sc.Dec 18 2023

In a recent review published in the journal Nature Reviews Gastroenterology and Hepatology, researchers discuss the influence of the maternal microbiome on the maternal, fetal, and early neonatal immune systems during pregnancy.

Study: The maternal gut microbiome in pregnancy: implications for the developing immune system. Image Credit: ArtFamily / Shutterstock.com

Background 

During pregnancy, significant changes in maternal immune, endocrine, and metabolic systems occur, which influences the gut, vaginal, and oral microbiota. These changes also impact placental and fetal development; however, the underlying mechanisms are not fully understood.

Numerous maternal and infant factors contribute to the establishment of the neonatal microbiome and immunity, which may impact long-term health outcomes such as non-communicable diseases, neural development, and susceptibility to infections. Additional research is needed due to the poorly understood mechanisms linking maternal microbiome changes to fetal and neonatal development, as well as the significant yet unclear influence of various maternal and infant factors on long-term health outcomes.

Interactions between the host microbiome during pregnancy

The gut microbiome undergoes significant changes during pregnancy, particularly during the later weeks of the third trimester. For example, increases in Proteobacteria and Actinobacteria, as well as reduced levels of short-chain fatty acids (SCFA) producing bacteria, have been observed, which lead to alterations in maternal obesity, inflammation, and insulin resistance.

Dietary changes can also lead to alterations in the microbial metabolites within their maternal microbiome. The maternal-mediated microbial metabolites are responsible for influencing the immunity of both the mother and the fetus.

Microbial-immune interactions during pregnancy

The interaction between the maternal and fetal immune systems at the maternal-placental interface is complex. Hofbauer cells, which are fetal macrophages, play an essential role in tissue homeostasis and immune response regulation.

Fetal T-cells, including memory T-cells, have also been identified, thus indicating early immune education in utero. Gut microbes modulate SCFAs, which leads to the control of T regulatory cells from mothers to support immune tolerance throughout pregnancy.

Fetal development involves the immune system being affected by maternal microbial metabolites. In fact, the maternal microbiota can affect offspring resistance or susceptibility to subsequent infection.

In humans, fetal intestines possess diverse metabolites involved in inflammation and neurodevelopment. The diversity of metabolites in the meconium serves as a marker of in-utero exposures and prenatal programming factors contributing to early-life gut microbiota composition.

Pregnancy complications

Pregnancy complications, particularly gestational diabetes mellitus (GDM), pre-eclampsia, and preterm birth (PTB), pose significant risks to both maternal and neonatal health. These conditions are closely associated with changes in the mother’s microbial environment that modulate immunity and metabolism; therefore, a better understanding of microbiome changes during pregnancy is crucial.

GDM

GDM, which is characterized by glucose intolerance that emerges during pregnancy, exemplifies the intricate interplay between maternal microbiome and metabolic health. This condition not only triggers inflammation but also induces substantial changes in the gut microbiome, which contribute to a cascade of metabolic and immune responses that adversely affect both the mother and fetus.

The metabolic profiles of women with GDM, as well as their neonates, exhibit significant differences as compared to those with healthy pregnancies. Thus, microbial dysbiosis in GDM may have long-term implications on the child's health that extend beyond gestation. 

Pre-eclampsia

Pre-eclampsia, which is a condition marked by high blood pressure and proteinuria, is another pregnancy complication with strong microbial underpinnings. Recent research points to significant alterations in the gut microbiome of women suffering from pre-eclampsia. These changes are not just limited to microbial composition but extend to functional aspects by affecting various metabolic pathways.

The altered microbial landscape in pre-eclampsia can lead to metabolite imbalances, some of which are microbial in origin. These disruptions may contribute to the pathophysiology of pre-eclampsia that potentially affects fetal development and increase the risk of future cardiovascular disorders. 

PTB

PTB, which is defined as childbirth occurring before 37 weeks of gestation, is closely associated with maternal microbial imbalances. Moreover, gut dysbiosis can trigger inflammatory processes within the uterus, thereby influencing maturation of the fetal immune system. This intrauterine inflammation often leads to a wide range of postnatal complications, which exemplifies the profound impact of maternal microbiota on neonatal health.

PTB is also associated with alterations in the neonate's microbiome, which further complicates the development of the infant’s immune system and increases their susceptibility to various health issues. 

Microbial-immune interactions after birth

The newborn transitions from a sterile environment to a microorganism-rich world at birth. Early microbial exposure affects immunity development, with specific microbial patterns influencing the neonatal immune system.

Breastfeeding supports this process by providing immune compounds, microorganisms, and metabolites that shape the infant's gut microbiota and immune system. The transfer of maternal antibodies through breastfeeding also provides early mucosal immune protection. The interaction of breast milk components with the infant's immune system is crucial for developing tolerance and immune regulation.

Future directions

Understanding the role of the microbiome in pregnancy outcomes and immune modulation requires further investigation. Future research should explore microbial exposure effects, long-term impacts, dietary interventions, and specific microbial products that affect immune cells. New therapies like fecal microbiota transplantation (FMT) are being explored for modulating neonatal microbiota, especially following Cesarean-section births.

The maternal microbiome plays a crucial role in fetal and neonatal immune development and is influenced by diet, environmental factors, and pregnancy complications. Understanding these complex interactions is essential for developing targeted interventions to improve maternal and child health.