RT Journal Article SR Electronic T1 Microbial community assembly and metabolite profile of the gut microbiome in extremely low birthweight infants JF bioRxiv FD Cold Spring Harbor Laboratory SP 125922 DO 10.1101/125922 A1 Stephen Wandro A1 Stephanie Osborne A1 Claudia Enriquez A1 Claudia Bixby A1 Antonio Arrieta A1 Katrine Whiteson YR 2017 UL http://biorxiv.org/content/early/2017/04/10/125922.abstract AB Background The assembly of the intestinal microbiota of extremely low birthweight (ELBW) infants has an important impact on both immediate and long term health. ELBW infants are frequently given antibiotics which are likely to perturb the assembly of the microbiota. Health complications are not uncommon for ELBW infants; they face health crises including sepsis and necrotizing enterocolitis (NEC). Microbes are thought to be involved in the pathogenesis of NEC, but the mechanisms are unclear. New understanding of the importance of human milk oligosaccharides and the establishment of a Bifidobacteria-dominated gut microbiota early in infancy suggest that all preterm infants have abnormal microbial colonization. The initial assembly of intestinal microbial communities may have significant impact on immune development and lifelong health.Results We measured the bacterial composition and metabolite profile of 32 ELBW infants by 16S rRNA gene sequencing and untargeted gas chromatography mass spectrometry of fecal samples. Infants either remained healthy, developed late-onset sepsis, or developed necrotizing enterocolitis. The bacterial compositions were similar to what has been observed in other studies of preterm infants. Fecal samples are dominated by aero-tolerant bacterial species, specifically Enterococcus, Enterobacteriaceae, and Staphylococcus. Only three ELBW infants were colonized by Bifidobacteria. Fecal samples from infants who developed NEC were not distinguishable from other infant samples based on bacterial compositions (Permanova R2 < 0.001, p = 0.99) or metabolite profiles (Permanova R2 = 0.05, p= 0.24). Instead the bacterial composition (R2 = 0.63, p < 0.001) and metabolite profile (R2 = 0.43, p < 0.001) were highly personalized for each infant. There were not significant correlations between the bacterial composition and metabolite profiles of fecal samples (Mantel test r= 0.18, p < 0.001).Conclusions Although antibiotics likely contribute to the instability of the ELBW infant intestinal microbiota, personalized signatures of bacteria and metabolites are still clearly present. Neither the bacterial composition or metabolite profile was unique in cases of disease. While bacteria certainly contribute to the profile of metabolites present in feces, in these ELBW infants, significant correlations between bacterial relative abundances as determined by 16S rRNA gene sequencing and untargeted GC-MS metabolite profiles were not detectable.