Early-Life Host–Microbiome Interphase: The Key Frontier for Immune Development

Abstract

Human existence can be viewed as an “animal in a microbial world.” A healthy interaction of the human host with the microbes in and around us heavily relies on a well-functioning immune system. As development of both the microbiota and the host immune system undergo rapid changes in early life, it is not surprising that even minor alterations during this co-development can have profound consequences. Scrutiny of existing data regarding pre-, peri-, as well as early postnatal modulators of newborn microbiota indeed suggest strong associations with several immune-mediated diseases with onset far beyond the newborn period. We here summarize these data and extract overarching themes. This same effort in turn sets the stage to guide effective countermeasures, such as probiotic administration. The objective of our review is to highlight the interaction of host immune ontogeny with the developing microbiome in early life as a critical window of susceptibility for lifelong disease, as well as to identify the enormous potential to protect and promote lifelong health by specifically targeting this window of opportunity.

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

“…A central interface mediating these interactions is the intestinal lumen, which represents a unique ecological environment that is the major site for microbial‐host crosstalk. Indeed, recent studies indicate that the microbiota, and certain microbiota members, modulate transcriptional and functional intestinal epithelial cell (IEC) responses through pathological and immune‐mediated mechanisms 7,8 . A central output of these interactions is the reinforcement of the gut barrier, which is achieved through constant replenishment of cells 9 .…”

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

“…A central interface mediating these interactions is the intestinal lumen, which represents a unique ecological environment that is the major site for microbialhost crosstalk. Indeed, recent studies indicate that the microbiota, and certain microbiota members, modulate transcriptional and functional intestinal epithelial cell (IEC) responses through pathological and immune-mediated mechanisms [6,7]. A central output of these interactions is the reinforcement of the gut barrier, which is achieved through constant replenishment of cells [8].…”

Potential Elimination of Human Gut Resistome by Exploiting the Benefits of Functional Foods

“…In contrast to previous beliefs that newborns were free of bacteria, it is now a proven fact that bacteria are present in the endometrium, amniotic fluid, umbilical cord, and meconium (Amenyogbe et al, 2017), and different environmental factors, such as the delivery mode (cesarean or vaginal), feeding style (breastfeeding or formula), gestational age, administration of probiotics or prebiotics, diet, exercise, geography, genetics, and air pollution are the most pivotal determinants for gut microbiota modifications that lead to the development of a mature and healthy gut (Bezirtzoglou and Stavropoulou, 2011;Koren et al, 2013;Tanaka and Nakayama, 2017;Thursby and Juge, 2017;Angelakis and Raoult, 2018;Avelar Rodriguez et al, 2018;Ficara et al, 2018;Leoni et al, 2019). It's quite controversial whether the human placenta includes microbes.…”