Mother’s Milk: A Purposeful Contribution to the Development of the Infant Microbiota and Immunity

The mammalian gastrointestinal tract harbors a complex ecosystem consisting of countless bacteria in homeostasis with the host immune system. Shaped by evolution, this partnership has potential for symbiotic benefit. However, the identities of bacterial molecules mediating symbiosis remain undefined. Here we show that, during colonization of animals with the ubiquitous gut microorganism Bacteroides fragilis, a bacterial polysaccharide (PSA) directs the cellular and physical maturation of the developing immune system. Comparison with germ-free animals reveals that the immunomodulatory activities of PSA during B. fragilis colonization include correcting systemic T cell deficiencies and T(H)1/T(H)2 imbalances and directing lymphoid organogenesis. A PSA mutant of B. fragilis does not restore these immunologic functions. PSA presented by intestinal dendritic cells activates CD4+ T cells and elicits appropriate cytokine production. These findings provide a molecular basis for host-bacterial symbiosis and reveal the archetypal molecule of commensal bacteria that mediates development of the host immune system.

The evidence that breastfeeding improves cognitive development is based almost entirely on observational studies and is thus prone to confounding by subtle behavioral differences in the breastfeeding mother's behavior or her interaction with the infant. To assess whether prolonged and exclusive breastfeeding improves children's cognitive ability at age 6.5 years. Cluster-randomized trial, with enrollment from June 17, 1996, to December 31, 1997, and follow-up from December 21, 2002, to April 27, 2005. Thirty-one Belarussian maternity hospitals and their affiliated polyclinics. A total of 17,046 healthy breastfeeding infants were enrolled, of whom 13,889 (81.5%) were followed up at age 6.5 years. Breastfeeding promotion intervention modeled on the Baby-Friendly Hospital Initiative by the World Health Organization and UNICEF. Subtest and IQ scores on the Wechsler Abbreviated Scales of Intelligence, and teacher evaluations of academic performance in reading, writing, mathematics, and other subjects. The experimental intervention led to a large increase in exclusive breastfeeding at age 3 months (43.3% for the experimental group vs 6.4% for the control group; P < .001) and a significantly higher prevalence of any breastfeeding at all ages up to and including 12 months. The experimental group had higher means on all of the Wechsler Abbreviated Scales of Intelligence measures, with cluster-adjusted mean differences (95% confidence intervals) of +7.5 (+0.8 to +14.3) for verbal IQ, +2.9 (-3.3 to +9.1) for performance IQ, and +5.9 (-1.0 to +12.8) for full-scale IQ. Teachers' academic ratings were significantly higher in the experimental group for both reading and writing. These results, based on the largest randomized trial ever conducted in the area of human lactation, provide strong evidence that prolonged and exclusive breastfeeding improves children's cognitive development. isrctn.org Identifier: ISRCTN37687716.