The physiological breast-milk proteins S100A8 and S100A9 promote an eubiotic gut state in infants

Technology Description

The S100 calcium binding proteins S100A8 and S100A9, and their extracellular heterocomplex, S100A8–A9, also known as calprotectin, are expressed by lamina propria macrophages in intestinal tissues from infants at higher levels than in intestinal tissues from adults and are, additionally, found in high amounts in human breast milk. High fecal levels of S100 proteins, from 30 days to 1 year of age, were associated with higher abundance of beneficial Actinobacteria and Bifidobacteriaceae, and lower abundance of Gammaproteobacteria, particularly opportunistic Enterobacteriaceae, in the neonate’s gut microbiome. In term infants, fecal S100A8-A9 levels are significantly higher during the first 3 months of life compared with normal adult values and normalize along with weaning until the end of the first year. In preterm infants, initial fecal S100A8-A9 levels are significantly lower than in term infants but increase during the first month of life. Breast milk is one important source of fecal S100A8-A9 in newborns and essentially supplements the endogenous S100A8-A9 production by neonatal macrophages. The clinical relevance is corroborated by strong associations of neonatal fecal S100A8-A9 deficiency with dysbiosis-linked diseases like NEC, sepsis, and long-term development of obesity, which can experimentally be prevented by a single nutritional supply of S100A8 at birth.