Editors' ChoiceINTESTINAL HOMEOSTASIS

Got Milk Antibodies?

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Science Translational Medicine  12 Mar 2014:
Vol. 6, Issue 227, pp. 227ec45
DOI: 10.1126/scitranslmed.3008862

Bookstores are bursting with manuals on how to forge healthy relationships—between husbands and wives, parents and children, boyfriends, girlfriends, or long-distance friends. But scientists have only recently begun to explore a different kind of human relationship: the one between the gut microbiome and the mammalian host immune system. Here, a healthy connection helps to sustain intestinal homeostasis for protection from infection and inflammation and maintenance of intestinal barrier function. Mom’s breast milk provides the first antibody-mediated immune protection for the gastrointestinal tracts of suckling infants in the form of secretory immunoglobulin A (SIgA), which is transported into the infant’s blood via the gut polymeric Ig receptor (pIgR). Now, Rogier et al. use genetically altered mice to evaluate the long-term effects of breast milk–derived SIgA on the development of the mammalian gut microbiome and host intestinal immunity.

Using pIgR-sufficient and pIgR-deficient mice to evaluate the effects of early exposure to passive maternal SIgA, the authors found that in pIgR-sufficient offspring, SIgA was derived exclusively from breast milk during the suckling period. After weaning, IgA produced by cells in the intestinal lamina propria was transported into the gut lumen via pIgR. Immunohistochemical analysis confirmed that this beneficial effect of breast milk–derived SIgA persisted after weaning up to adulthood. Early exposure of suckling mouse neonates to passive SIgA through breast milk defended pIgR-sufficient, but not pIgR-deficient, neonates against the invasion of opportunistic pathogens translocated from the gut to mesenteric lymph nodes. pIgR-deficient weanling mice, which did not receive passive SIgA in breast milk, displayed compromised epithelial barrier function and invasion of opportunistic aerobic bacteria in the gut lumen. Furthermore, weaned mice that had received SIgA from breast milk housed a different gut microbiota and displayed distinct intestinal epithelial cell gene expression relative to mice that did not receive maternal SIgA, which was also found to heal colonic epithelium damaged by chemically induced gastroenteritis.

These results suggest that maternal immunoglobulins improve the intestinal immune system of breast-fed infants and that this effect persists into adulthood. The new work may spur the exploration of purified oral SIgA as a biological therapy for intestinal inflammation among formula-fed infants and with SIgA-deficient young children. However, further evidence is required to establish a firm link between breastfeeding and maintenance of intestinal homeostasis during the transition from weaning to adulthood.

E. W. Rogier et al., Secretory antibodies in breast milk promote long-term intestinal homeostasis by regulating the gut microbiota and host gene expression. Proc. Natl. Acad. Sci. U.S.A. 111, 3074–3079 (2014). [Full Text]

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