S100A12 and hBD2 Correlate with the Composition of the Fecal Microflora in ELBW Infants and Expansion of E. coli Is Associated with NEC

OBJECTIVE To describe the development of the gut microbiota in extremely low birth weight (ELBW) infants with and without necrotizing enterocolitis (NEC) between April 2008 and December 2009, fecal microflora was prospectively analyzed in fecal samples of all ELBW infants using real-time PCR assays. In addition, fecal inflammatory were measured. RESULTS Fecal microflora established early in ELBW infants and microbiota composition remained stable over the first 28 days of life except for the prevalence of C. difficile which decreased with decreasing antibiotic use. Infants who subsequently developed NEC had an increase of total bacterial count (9.8-fold) 24 h prior to clinical symptoms mainly due to the expansion of E. coli species (21.6-fold), whereas microbiota composition did not differ from healthy ELBW infants five days before onset of NEC. Importantly, S100A12 and hBD2 positively correlated with the total and E. coli bacterial CFU/g feces (r (2) 0.4 and 0.64, resp.). CONCLUSIONS In summary, we found evidence for a disturbed homeostasis between the intestinal microbiome and host immunity in ELBW infants with NEC. Moreover, S100A12 and hBD2 correlate with the fecal microbiota thus linking the intestinal innate immune response to the bacterial colonization thus possibly providing a diagnostic tool in the future.