Programmed and environmental determinants driving neonatal mucosal immune development

Intergenerational protective anti-gut commensal immunoglobulin G originates in early life

“…The gut microbiota is dynamic in early life and impacts immune development on multiple levels. Thus, controlling immune exposure to the gut commensal bacteria is complex, and manipulating early-life intestinal commensals could have multiple off-target effects given the central role of the microbiota in normal immune development ( 16 ). We therefore complemented these studies with a time-limited pre-weaning exposure of dietary ovalbumin (OVA), which is transferred from mothers to their pups via breastmilk ( 16 , 24 ) to confirm that IgGs specific for luminal antigens can be generated during early life and persist into adulthood.…”

“…Thus, controlling immune exposure to the gut commensal bacteria is complex, and manipulating early-life intestinal commensals could have multiple off-target effects given the central role of the microbiota in normal immune development ( 16 ). We therefore complemented these studies with a time-limited pre-weaning exposure of dietary ovalbumin (OVA), which is transferred from mothers to their pups via breastmilk ( 16 , 24 ) to confirm that IgGs specific for luminal antigens can be generated during early life and persist into adulthood. Early-life exposure to dietary OVA induces long-lasting OVA-specific T regulatory cells (Tregs) originating in the colon, similar to gut bacteria-specific Tregs generated at this time in life ( 24 ).…”

“…In early life, the immune system and gut microbiota co-develop and are co-dependent. The “neonatal window of opportunity” ( 16 ) is a choreographed series of events, which includes the delivery to the immune compartment of microbial antigens through goblet cell–associated antigen passages (GAPs) ( 17 ). In mice prior to day of life (DOL) 10, colonic GAP formation is inhibited by high levels of epidermal growth factor (EGF) in the breastmilk.…”

Probiotics induce intestinal IgA secretion in weanling mice potentially through promoting intestinal APRIL expression and modulating the gut microbiota composition

“…1,2 Initially, infants rely on passive immunity provided by maternal IgA through breast milk; however, this protective effect of maternal IgA diminishes upon weaning, necessitating the active production of IgA in infants to maintain intestinal protection. 3 Although the production of intestinal IgA increases significantly after weaning, human infants do not reach adult IgA levels until the age of 2–3 years. 4,5 The low expression of intestinal IgA levels greatly increases the susceptibility to intestinal infections, and intervention in mice effectively enhances IgA expression in the jejunal or ileal mucosa and strengthens their resistance to intestinal infections after weaning.…”

Early-life exposures to specific commensal microbes prevent type 1 diabetes

“…Indeed, disruption of the microbiota, specifically around weaning, leads to profound susceptibility to immune dysfunction later in life ( 14 ). In humans, early-life perturbations of key host-microbe interactions are associated with an increased risk of diseases such as allergy, asthma, psoriasis, obesity, and inflammatory bowel disease ( 9, 10, 27 ). Epidemiologic and experimental studies suggest that the same is true for T1D ( 28–31 ).…”