Sex-specific gut microbiome profiles among preterm infants during the neonatal intensive care hospitalization.

Objectives: The gut microbiota among preterm infants is shaped by sex and feeding types. However, sex-specific weekly patterns of gut microbiome profiles among preterm infants during their neonatal intensive care unit (NICU) hospitalization remain unclear. This study aimed to investigate the effect of sex on the weekly development of preterm neonatal gut microbiota in the first 4 weeks of NICU hospitalization.

Methods: This secondary data analysis included 28 preterm neonates with 261 stool samples collected from January 2014 to February 2015 in the Northeastern United States. The 16S rRNA V4 gene regions of the stool samples were sequenced and aligned against the SILVA 132 database by using Mothur 1.42.3. The sex-specific weekly diversity indexes and relative abundance of bacterial taxonomic composition were generated by Mothur and analyzed by R packages. Sex-specific weekly compositional patterns of the gut microbiome and predicted metabolic functions of gut microbiome profiles were compared, respectively.

Results: In each week of the NICU hospitalization, preterm females and males had significantly distinguished β-diversity indices and compositions of gut microbiota. Both females and males had significantly enriched , a protection feature, in stool samples collected in the third week compared with those in the second week. The predicted metabolic pathways were significantly different between females and males in the second, third, and fourth week of the NICU hospitalization. Both females and males had significantly abundant pathways. Males consistently had more abundance of "lipopolysaccharide biosynthesis" than females in the second, third, and fourth week. Males also had a significant abundance of "membrane and intracellular structural molecules" and "glycan biosynthesis and metabolism" in the second and third week.

Conclusions: Sex shaped the weekly patterns of preterm neonatal gut microbiome profiles during the first 4 weeks of the NICU hospitalization. Further clinical interventions should consider the distinct gut microbiota compositions and predicted functional profiles between female and male preterm neonates.