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Development of the preterm infant gut microbiome: a research priority

Abstract: The very low birth weight (VLBW) infant is at great risk for marked dysbiosis of the gut microbiome due to multiple factors, including physiological immaturity and prenatal/postnatal influences that disrupt the development of a normal gut flora. However, little is known about the developmental succession of the microbiota in preterm infants as they grow and mature. This review provides a synthesis of our understanding of the normal development of the infant gut microbiome and contrasts this with dysbiotic development in the VLBW infant. The role of human milk in normal gut microbial development is emphasized, along with the role of the gut microbiome in immune development and gastroenteric health. Current research provides evidence that the gut microbiome interacts extensively with many physiological systems and metabolic processes in the developing infant. However, to the best of our knowledge, there are currently no studies prospectively mapping the gut microbiome of VLBW infants through early childhood. This knowledge gap must be filled to inform a healthcare system that can provide for the growth, health, and development of VLBW infants. The paper concludes with speculation about how the VLBW infants’ gut microbiome might function through host-microbe interactions to contribute to the sequelae of preterm birth, including its influence on growth, development, and general health of the infant host.

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Alex’s Notes: The gut microbiome is no stranger in the health and medical fields. At one point it was virtually unknown to exist, and now it seems to penetrate every aspect of our wellbeing. While everyone who is able to appreciate its complexity and importance are at an age where shifts are subtle, external factors play a far more pronounced role in shaping our symbiotic relationship while we are young. No doubt, the native microbiome in human milk could have profound influences on how we alter early gut microbiome development.

At one point, infants were through to be born sterile, although emerging evidence suggests otherwise. When born vaginally, infants are rapidly colonized by the maternal vaginal, intestinal, skin, and milk microorganisms. Conversely, C-section babies have bacterial communities more similar to those found on the skin, and may even have lower microbial diversity down the road when compared to vaginally delivered babies. Regardless, it takes roughly three years before the gut microbes resemble that of an adult human.

Why the lag time? Likely it has to do with breast milk and its HMOs (human milk oligosaccharides) that nurture both the growing infant and bacterial colonies, while more adult foods require a different diversity of microbes to handle it. Indeed, breast-fed infants have nearly twice the abundance of intestinal bacterial cells, but less diversity, than formula-fed infants. Moreover, formula-fed infants have a microbiome that more closely resembles that of infants consuming solid foods. No doubt, breast milk is a powerhouse full of pro- and prebiotic compounds that serve to populate the infant gut, which in turn interacts with the immune system to induce apoptotic stimuli, reactive oxygen synthesis, and Toll-like receptor (TLR) signaling that ultimately produces a state of controlled inflammation that helps develop the innate immune defenses and promotes pathogen recognition.

This brings me to the purpose of the current review. The authors suggest that

“The early microbiome is likely to determine the signature of the adult microbiome, based on the founder effect, whereby the original colonizing microbiota are instrumental in the successional direction of the assemblage. As a result, the initial colonizing microbiota is likely to be a critical determinant in the development of certain pediatric diseases [30]. The early microbiota produces active metabolites such as folate, butyrate, and acetate, which could epigenetically alter gut epithelium and hepatic and immune cells, a type of developmental programming which might later translate into risks for a variety of human diseases, including obesity [31].”

As such, there is a distinct lack of research looking into how preterm births may impact normal developmental pathways of the infant and its bacteria. It has been demonstrated that very low birth weight (VLBW) infants – a common side-effect of being preterm – have very different types of bacteria than full-term infants. Moreover, they often display a delay in establishing an adult microbiota, which may preempt gastrointestinal and immunological problems that effect neurodevelopment in childhood and later life.

The above is possibly a result of the common insults many preterm infants experience. The infants can be exposed to many inflammatory factors in utero (prenatal maternal illness, infections such as bacterial vaginosis and chorioamnionitis, smoking and physiological stress) and postnatally (formula feeding, invasive procedures, antibiotics and medications that alter gastrointestinal pH), and may experience extremely different microbial sources as they often go through rapid vaginal of C-section deliveries that reduce “first contact” of maternal microbes.One recent longitudinal study of two VLBW infants found that the gut microbiome was influenced by microorganisms in the NICU environment, and antibiotic-resistant microbes were colonizing these infants’ guts.

When the above is taken in consideration with the numerous studies demonstrating increased disease risk in preterm infants, the author’s conclusions are very much a call to action. Yes, we are still in the infancy of understanding the gut. However, it is becoming increasingly clear that the early infant gut microbiome is an important regulator of many developing physiologies. Thus,

“The VLBW infant is disadvantaged in many ways, including the likely development of dysbiosis of the gut microbiome. Exploration of the long-term effects of this abnormal microbial number, diversity, and succession has not yet been done and is critically needed in order to intervene both early and later in the lives of these children.”

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