Factors influencing microbiota development and maturation of the immune system early in life
Birth represents the biggest substantial environmental change in life as the newborn is exposed for the first time to a countless variety of microbes which colonize all body surfaces, leading to the establishment of the commensal microbiota in parallel with the immune system. Many factors shape the composition of the gut microbiota and the maturation of the newborn immune system (Fig 3). Discrepancies in the microbiota and immunity crosstalk during each developmental stage can have long-term effects on disease susceptibility.13
About this article
Birth impacts gut microbiota composition...
by Dr. Travis J. De Wolfe
The mode of delivery impacts what type of bacteria from the mother are transmitted to the neonatal intestine.14 Babies delivered via the birth canal often carry many gut bacteria that synthesize lipopolysaccharide (LPS), a major membrane component of Gram-negative bacteria that can properly train the human immune system to properly respond to microbial threats.15 In contrast, children delivered by caesarean section are predisposed to being colonized by opportunistic pathogens that circulate in hospitals.14
…As well as maturation of immune structure
These differences in initial microbial colonization can affect the subsequent maturation of the local innate lymphoid structures and alter the population of protective regulatory T cells (Treg), resulting in long-term effects on human intestinal physiology. Maturation of T cells and induction of immune factors can protect against, or in some cases, contribute to autoimmune-mediated diseases (diabetes, multiple sclerosis…) that develop later in life.15,16
FIGURE 3: Environmental factors influencing the development of the newborn microbiota and mucosal immune system.
Adapted from Kalbermatter C et al, 202113
Throughout pregnancy, microbial metabolites (originating from the maternal microbiota and diet) influence fetal immune development. At birth, microbiota colonization starts in parallel with development of the immune system. At this stage, the newborn is still dependent on maternal protection, which is ensured through breastfeeding: maternal milk contains mother-derived bacterial antigens that stimulate the maturation of the innate mucosal immune system. Regarding gut microbiota colonization, Enterococcacae, Clostridiaceae, Lactobacillaceae, Bifidobacteriaceae, Streptococcaceae dominate in the first weeks of life. The introduction of solid food in an infant’s diet leads to an increase in gut microbiota diversity, evolving to a more adult-like microbiota: the abundance of Bifidobacteriaceae decreases, while Bacteroides, Ruminococcus, and Clostridium become more prevalent. Birth mode, breast milk, solid food, and the intake of antibiotics are factors that shape the early life microbiota and the neonatal immune system.
18 Costelloe C, Metcalfe C, Lovering A, et al. Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis. BMJ. 2010 May 18;340:c2096.
25 Yang C, Mogno I, Contijoch EJ, et al. Fecal IgA Levels Are Determined by Strain-Level Differences in Bacteroides ovatus and Are Modifiable by Gut Microbiota Manipulation. Cell Host Microbe. 2020 Mar 11;27(3):467-475.e6.