THE PRETERM INFANT GUT MICROBIOME, HUMAN MILK VOLUME AND IMMUNOBIOLOGY, AND GROWTH

Abstract

We conducted a study of gut microbiome in very low birth weight (VLBW) infants along with measures of milk feedings (type and volume) and milk sIgA, cytokines and chemokines for six weeks after admission in 78 infants. Stools were collected weekly, and human milk collected daily and pooled weekly for a panel of immune markers. Mothers of these infants gave informed consent and the study was approved by the university IRB. Mean levels of sIgA, EGF, MIP1α, IP10, MCP1, IL‐8, IL‐4, IL‐6, IL‐10 and TNFα were measured each week for six weeks by MagPix.4.2. Stool DNA was extracted using MoBio kits, the V3–V4 region of the 16S rRNA gene was amplified and then sequenced on an Illumina MiSeq.These infants had a mean gestation age at birth of 28 weeks, 3 days, and a mean birth weight of 1078 Gms. The mean time to full enteral feeding was 12 days, and they were fed mothers own milk (MOM), donor milk or preterm infant formula in varying amounts. The infant stool demonstrated marked dysbosis over time, with a dominance of Gram negative Gammaproteobacteria. Mean levels of sIgA, EGF, MIP1α, IP10, MCP1, IL‐8, IL‐4, IL‐6, IL‐10 and TNFα were measured each week for six weeks. Data reported here are mean Shannon diversity, and mean number of operational taxonomic units (OTUs) over the first six weeks of admission to the NICU, the ratio of human milk volumes to total feed volumes, the mean concentrations of milk immune markers over the 6 weeks of measurement, and the relationship between growth and the microbiome in these infants.Shannon diversity significantly increased with increasing corrected gestational age (cGA) (Multiple R2: 0.09221, p= 1.28e‐08). Adjusting for cGA during the NICU stay, the alpha diversity also showed weak but significant correlations with overall rate of weight gain (Multiple R2: 0.144, p=0.00208) and total ratio of mother's own milk (Multiple R2: 0.1097, p = 0.024918).Over the 6 weeks of admission, the mean number of fecal OTUs was correlated with mean milk IL‐4 (pg/ml) (r=.25, p=.03), but no other milk immune markers. The time to enteral feeding was inversely correlated to the number of OTUs (r=‐.24, p=.036). Lower diversity was observed in infants with lower gestational age (t=.31, p=.006), sepsis (t=2.43, p=.017), and days on oxygen (r=.23, p=.04).This is the first study to show that growth of VLBWs may be influenced by the microbiome in these early weeks of life. There were few relationships between specific immune markers and gut microbiome, but the amount of MOM an infant receives may partially ameliorate the dysbiosis.Future studies are planned to investigate the growth/nutrition/microbiome relationship in VLBWs as they grow and develop into early school age.Support or Funding InformationNIH R01NR15546This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.