Disrupted Maturation of the Microbiota and Metabolome among Extremely Preterm Infants with Postnatal Growth Failure

Growth failure during infancy is a major global problem that has adverse effects on long-term health and neurodevelopment. Preterm infants are disproportionately affected by growth failure and its effects. Herein we found that extremely preterm infants with postnatal growth failure have disrupted maturation of the intestinal microbiota, characterized by persistently low diversity, dominance of pathogenic bacteria within the Enterobacteriaceae family, and a paucity of strictly anaerobic taxa including Veillonella relative to infants with appropriate postnatal growth. Metabolomic profiling of infants with growth failure demonstrated elevated serum acylcarnitines, fatty acids, and other byproducts of lipolysis and fatty acid oxidation. Machine learning algorithms for normal maturation of the microbiota and metabolome among infants with appropriate growth revealed a pattern of delayed maturation of the microbiota and metabolome among infants with growth failure. Collectively, we identified novel microbial and metabolic features of growth failure in preterm infants and potentially modifiable targets for intervention

Hormonal Determinants of Growth and Weight Gain in the Human Fetus and Preterm Infant

The factors controlling linear growth and weight gain in the human fetus and newborn infant are poorly understood. We review here the changes in linear growth, weight gain, lean body mass, and fat mass during mid- and late gestation and the early postnatal period in the context of changes in the secretion and action of maternal, placental, fetal, and neonatal hormones, growth factors, and adipocytokines. We assess the effects of hormonal determinants on placental nutrient delivery and the impact of preterm delivery on hormone expression and postnatal growth and metabolic function. We then discuss the effects of various maternal disorders and nutritional and pharmacologic interventions on fetal and perinatal hormone and growth factor production, growth, and fat deposition and consider important unresolved questions in the field

Additional file 1: of Early-life skin microbiota in hospitalized preterm and full-term infants

Table S1. Raw sequencing reads, OTUs, and genera per sample by sample type. (DOCX 13 kb

Additional file 2: of Early-life skin microbiota in hospitalized preterm and full-term infants

Figure S1. Contaminant OTUs identified in extraction control samples. A. Relative abundance of bacterial taxa in extraction control samples. B. OTUs with greater than 1% relative abundance in extraction controls. These OTUs were excluded from subsequent analyses as they were presumed to be contaminants, except the highlighted Staphylococcus OTU that was found to be the dominant Staphylococcus OTU in the biological samples. C. Relative abundance of the contaminant OTUs (in aggregate) that were excluded from subsequent analyses within each sample site. The contaminant OTUs contributed to a minority of the total OTU abundance in each of the sample sites. OTU = operational taxonomic unit. (PPTX 264 kb

Additional file 5: of Early-life skin microbiota in hospitalized preterm and full-term infants

Figure S3. Skin and oral microbiota of twin pairs. A. Characteristics of the five twin pairs that were included in the study are shown, including the gestational age (preterm or full-term), the postnatal age (in days) at the time of sample collection, and the percentage of oral and skin OTUs that were shared between the infants in each twin pair. The relative abundance of the top bacterial genera within the skin and oral microbiomes are shown for the individual infants (Twin A, Twin B) within each twin pair (Twin Pairs 1–5). B. Principal coordinates analysis of samples from the twins based on generalized UniFrac distances. The twin pairs (1–5) are grouped by color. (PPTX 363 kb

Additional file 8: of Early-life skin microbiota in hospitalized preterm and full-term infants

Figure S4. The environmental microbiota of preterm and full-term infants. A. Relative abundance of the top genera in the hospital environment. B. Generalized UniFrac distances between infant body sites and their corresponding environmental samples. Median distances were lower among preterm infants. *p < 0.05. (PPTX 118 kb

Additional file 4: of Early-life skin microbiota in hospitalized preterm and full-term infants

Figure S2. Principal coordinates analysis (PCoA) of samples across body sites. PCoA of infant samples excluding contaminant OTUs (A, B) or including contaminant OTUs (C, D). Similar relationships between body sites are seen using generalized UniFrac distances (A, C) and Bray-Curtis distances (B, D). In panel C, the first and second axes are rotated to keep the orientation of samples consistent with the other panels, but it should be noted that the vertical axis accounts for the majority of the variation between samples in this panel. (PPTX 717 kb

Additional file 6: of Early-life skin microbiota in hospitalized preterm and full-term infants

Table S3. Bacterial taxa with differences in abundance between body sites. (DOCX 12 kb

Additional file 3: of Early-life skin microbiota in hospitalized preterm and full-term infants

Table S2. Diagnoses and morbidities among infants admitted to the neonatal intensive care unit. (DOCX 12 kb