Differential Effects of Mother\u27s Own Milk, Donor Human Milk and Formula Feeding on the Fecal Microbiota of Preterm Infants During Their Stay in the Neonatal Intensive Care Unit

Objectives: Preterm infants (PTI) are at risk for many complications including growth retardation, and co-morbidities, such as necrotizing enterocolitis. Microbiome composition is influenced by diet and other environmental factors or medical treatments. The use of mother\u27s own milk (MOM) or donor human milk (DHM) is recommended over preterm formula (PF). However, when there is insufficient human milk (HM), PF is used. The objective of this study was to evaluate how each type of feed (MOM, DHM and PF) affects PTI gut microbiota composition during the infant\u27s Neonatal Intensive Care Unit (NICU) stay. Methods: This cohort study followed PTI from birth until discharge from the NICU. Medical records, weekly weight and daily feed volume were recorded. Stool samples (n = 551) were collected from the infant\u27s diaper. Total DNA was extracted to assess microbiome composition, V3-V4 regions of 16S rRNA gene were amplified and sequenced using Illumina HiSeq and data were analyzed in Qiime2. Results: PTI (n = 97; 63% female) were enrolled with mean gestational age (GA) of 29 ± 2.45 weeks, birth weight of 1.27 ± 0.43 kg, and 78% delivered by C-section. Infants were discharged at 37 ± 2.06 weeks corrected GA (cGA) weighing 2.69 ± 0.57 kg. At birth, PTI from black mothers (27%) had higher (P \u3c 0.05) microbiota diversity (observed OTUs) than other ethnicities. No differences in microbiota were found for sex or mode of delivery in the first 14d postpartum. PF was not fed prior to 34 weeks cGA. Over time, microbiota beta diversity differentiated by cGA and type of feeding. In HM-fed PTI, when \u3e 50% MOM was consumed, the abundance of Clostridium, Enterococcus, and Staphylococcus was higher (P \u3c 0.05) than DHM. When \u3e 50% DHM was fed, Bifidobacteium, Paeniclostridium, Staphylococcus and Veillonela increased (P \u3c 0.05) compared to \u3e 50% MOM. In PTI fed both HM and PF, in those consuming \u3e 33% PF, the abundance of Clostridium difficile was higher and Staphylococcuslower than either MOM or DHM (P \u3c 0.05). Conclusions: The development of fecal microbiota of PTI was modulated by cGA, such that abundance and diversity increased over time. The fecal microbiota was differently modified by consumption of human milk, either MOM or DHM, versus PF. Ongoing studies are investigating the effect of milk fortifiers and other NICU environmental factors on the gut microbiota