The Microbiome and Preterm Birth: A Change in Paradigm with Profound Implications for Pathophysiologic Concepts and Novel Therapeutic Strategies

Abstract

Preterm birth poses a global challenge with a continuously increasing disease burden during the last decades. Advances in understanding the etiopathogenesis did not lead to a reduction of prematurely born infants so far. A balanced development of the host microbiome in early life is key for the maturation of the immune system and many other physiological functions. With the tremendous progress in new diagnostic possibilities, the contribution of microbiota changes to preterm birth and the acute and long-term sequelae of prematurity have come into the research focus. This review summarizes the latest advances in the understanding of microbiomes in the amniotic cavity and the female lower genital tract and how changes in microbiota structures contribute to preterm delivery. The exhibition of these highly vulnerable infants to the hostile environment in the neonatal intensive care unit necessarily entails the rapid colonization with a nonbalanced microbiome in a situation where the organism is still very prone and at an early stage of development. The global research efforts to decipher pathologic changes will pave the way to new pre- and postnatal therapeutic concepts.

Figure 1

Origin of microbiota in the amniotic cavity leading to preterm birth: The microbiome in the amniotic cavity has long been thought to originate exclusively from the vaginal and cervical microbiome. But microbiota from the oral cavity, gut, and even the placenta provide a substantial contribution to the microbiome in the amniotic cavity mainly via haematogenic spread.

Figure 2

Impact of gut microbiota on the acute and long-term morbidities in the preterm infant: The gut microbiota exerts a central influence on human health. In the preterm infant, their impact on NEC and nosocomial infection is well recognized. First studies hint to an important impact on somatic growth, psychomotor development, autonomic regulation, and hormonal balance. In contrast, the contribution to the other acute and long-term sequelae remains to be determined.

Figure 3

Factors determining the composition of gut microbiota in the preterm infant: The microbiome of the gastrointestinal tract of the preterm infant varies widely from that at term and is impacted by a plenty of endogenous and environmental factors and pre- and postnatal therapeutic interventions.