Impacts of Enriched Human Milk Cells on Fecal Metabolome and Gut Microbiome of Premature Infants with Stage I Necrotizing Enterocolitis: A Pilot Study

Abstract

Scope: Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in preterm infants, occurring more often in formula-fed infants than in breastfed infants. Recent animal studies have shown that cells in fresh breast milk survive in the newborns' digestive tract. However, no clinical studies have been conducted on the effects of human milk cells, and their biological roles in the infants' intestines remain unexplored. Methods and Results: Twenty premature infants are enrolled. Cells from fresh milk of their own mothers are enriched and fed to infants with Bell's Stage I NEC once a day for 7 days since the onset of NEC. Fecal samples are collected at enrollment and 2 weeks later. Fecal sphingolipids are observed to be enriched in NEC patients and positively correlated with calprotectin levels. After intervention with enriched human milk cells, inflammation-associated sphingolipids and microbiome profiles are altered and resembled those of the controls. Conclusion: These preliminary findings reveal the potential impacts of enriched human milk cells on premature infants with Bell's Stage I NEC and provide insight into the roles of fecal sphingolipid metabolism in the neonates' intestinal inflammation. However, the limited sample size of the study indicates the need for further investigation.

Dynamics and Crosstalk between Gut Microbiota, Metabolome, and Fecal Calprotectin in Very Preterm Infants: Insights into Feeding Intolerance

“…The 16S rRNA sequencing and raw data preprocessing were processed according to the standard protocols provided by Majorbio Bio-Pharm Technology Co., Ltd. (Shanghai, China), as previously described [30]. In brief, microbial genomic DNA was isolated from each fecal specimen using the E.Z.N.A.…”

Pathogen-specific alterations in intestinal microbiota precede urinary tract infections in preterm infants: a longitudinal case-control study

“…The 16S rRNA sequencing and raw data preprocessing were processed according to the standard protocols provided by Majorbio Bio-Pharm Technology Co. Ltd. (Shanghai, China), as previously described. 28 In brief, microbial genomic DNA was isolated from each fecal specimen using the E.Z.N.A. Soil DNA Kit (Omega Bio-Tek, Norcross, GA, U.S.) according to the manufacturer’s instructions.…”

Metabolomic Diversity of Human Milk Cells over the Course of Lactation—A Preliminary Study

“…The authors further suggest that although HM cells may not survive digestion, they still might be taken up by phagocytic cells or shed extracellular vesicles that can be taken up by the intestinal epithelium. At the same time, feeding interventions with cell-enriched HM in preterm infants with Bells's stage I NEC have shown to successfully normalize fecal sphingolipids and the gut microbiome profiles resembling those of healthy controls [14]. In this regard, the role of metabolites of the HM cell fraction in achieving the benefits of breastfeeding remains so far unexplored.…”