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Genetic Variation in SLC30A2 and Associated Alterations in Enteric Microbiota in Preterm Infants

Necrotizing enterocolitis (NEC) is a devastating intestinal disease of preterm infants. Defects in Paneth cells (PC), which are specialized secretory cells that release antimicrobial peptides, cytokines, and zinc (Zn) to maintain enteric microbiota, are associated with NEC. We recently found that the Zn transporter ZnT2 (SLC30A2) is critical for PC function and that non‐synonymous genetic variation (GV) in SLC30A2 occurs in ~35% of the population. Here we aimed to determine if a relationship exists between GV in SLC30A2 and the composition of enteric microbiota in preterm infants. DNA and fecal samples were collected from 20 infants (mean gestational age 33 weeks). The entire coding region of SLC30A2 and fecal genomic DNA were sequenced. 74,332 sequences were retrieved and data revealed that the fecal microbial community was dominated by Enterobacteriaceae (44%). Three unknown species in the Enterobacteriaceae family strongly correlated (p<0.05) with a region of dense GV in the C‐terminus, after accounting for multiple testing via FDR correction. These species were each approximately 5‐fold more abundant in infants with GV than in those without. Recent studies highlight the importance of establishing normal microbiota after birth, especially in preterm infants. Because several members of Enterobacteriaceae are known pro‐inflammatory opportunistic pathogens, our study suggests that GV in SLC30A2 affects the establishment of normal microbiota, which could potentially increase risk for enteric infections.