Lessons from mother: Long-term impact of antibodies in breast milk on the gut microbiota and intestinal immune system of breastfed offspring

Abstract

From birth to adulthood, the gut microbiota matures from a simple community dominated by a few major bacterial groups into a highly diverse ecosystem that provides both benefits and challenges to the host. Currently there is great interest in identifying environmental and host factors that shape the development of our gut microbiota. Breast milk is a rich source of maternal antibodies, which provide the first source of adaptive immunity in the newborn's intestinal tract. In this addendum, we summarize our recent data demonstrating that maternal antibodies in breast milk promote long-term intestinal homeostasis in suckling mice by regulating the gut microbiota and host gene expression. We also discuss important unanswered questions, future directions for research in this field, and implications for human health and disease.

Keywords: breastfeeding; gene expression; gut microbiota; inflammatory bowel disease; intestinal epithelial cells; polymeric immunoglobulin receptor; secretory IgA.

Figure 1.

Breeding scheme for generating offspring mice exposed to breast milk-derived maternal SIgA and/or endogenous SIgA derived from intestinal epithelial transport of locally synthesized IgA.

Figure 2.

Hypothetical model of the role of breast milk-derived secretory (S)IgA in the development of intestinal immunity. (A) In the presence of maternal SIgA, gut microbes are concentrated in the loose outer layer of colonic mucus (shown here in light blue), while the dense inner layer of mucus (shown here in darker blue) is relatively devoid of both SIgA and microbes. Microbial products stimulate intestinal epithelial cells and promote a healthy balance between pro- and anti-inflammatory gene expression. (B) In the absence of maternal SIgA, the composition of the gut microbiota is altered, and some microbes penetrate the mucus and epithelial barriers to invade draining mesenteric lymph nodes. Intestinal dysbiosis can persist into adult life and result in imbalanced pro-inflammatory gene expression in intestinal epithelial cells.