Lungs, Microbes and the Developing Neonate

Abstract

Microbes are ubiquitous on the human body and comprise approximately 90% of the cells and 99% of the genes of the human supraorganism. High-throughput sequencing technology has permitted the development of culture-independent means to identify the microbiota that are unique to the various microenvironments of the body and probably contribute some function. Although the respiratory tract interfaces with the environment, the lungs were always thought to be a sterile environment - until recently, when these techniques were applied to healthy and disease states. Further, there appears to be a complex interplay between the development of the gastrointestinal and respiratory microbiota and the regulation of immune function. The contribution of this dynamic metabolic mass to respiratory disease in the newborn is unknown. This article will review emerging data from recent human and murine studies that suggest there is a microbial influence on the development of respiratory disease, but it will also highlight many of the gaps that remain in understanding the function of the respiratory microbiome.

Neonatal gut and respiratory microbiota: coordinated development through time and space

“…The gut and respiratory tracts in infants share the same embryonic origin, with mucosal surfaces composed of columnar epithelial cells that sense the commensal microbiota and in turn shape local and systemic immunity as infants mature and as a function of PMA [24-26, 35, 37]. Changes in infant gut and respiratory microbiota that occur as a result of diet, antibiotics, therapeutics and environmental exposures in the NICU are likely to influence the microbiota at both sites [32, 38, 39].…”

“…The occurrence of these chronic lung diseases is accompanied by functional and structural changes in the intestinal mucosa and increased intestinal permeability, suggesting that interactions between these two distal sites through the gut-respiratory axis impact adult health and disease [43, 45]. These gut-respiratory interactions likely function on several levels, ranging from direct transfer of bacteria between these sites through reflux and aspiration to indirect effects from bacterial metabolic products or mucosal immune responses common to both the gut and respiratory tract [33, 35, 37, 46]. Taken together, these observations of common developmental origins for the gut and respiratory tracts as well as inflammatory diseases that affect both sites, support potential systemic mechanisms that coordinate microbiota development at these distal sites in infants.…”

The lung microbiome in neonates

“…18 Short chain fatty acids (SCFA) produced by the gut microbes can also influence the fate of respiratory conditions. 25 As demonstrated by Trompette et al 26 in their study involving mice, a higher proportion of circulating SCFA can confer a protective effect against allergic disease development. Chen et al 27 were the first ones to report an inverse relationship between Helicobacter pylori and development of childhood asthma and this finding may be explained by the hygiene hypothesis.…”

Sterile Inflammation Enhances ECM Degradation in Integrin β1 KO Embryonic Skin

“…However, how these precursors and other immune cells contribute to immune surveillance during embryonic skin development is not completely understood. Most of our understanding of fetal immune development at the body's interface with the surrounding is derived from studies of the gastrointestinal system (McElroy and Weitkamp, 2011;Warner and Hamvas, 2015).…”