Effect of donor human milk on host-gut microbiota and metabolic interactions in preterm infants

Abstract

Background & aims: Human milk is the gold standard for infant nutrition. Preterm infants whose mothers are unable to provide sufficient own mother's milk (OMM), receive pasteurized donor human milk (DHM). We studied metabolic signatures of OMM and DHM and their effect on the interplay of the developing microbiota and infant's metabolism. Methods: Metabolic fingerprinting of OMM and DHM as well as infant's urine was performed using liquid chromatographyemass spectrometry and the infant's stool microbiota was analyzed by 16S rRNA sequencing. Results: Significant differences in the galactose and starch and sucrose metabolism pathways when comparing OMM and DHM, and alterations of the steroid hormone synthesis and pyrimidine metabolism pathways in urine were observed depending on the type of feeding. Differences in the gut-microbiota composition were also identified. Conclusion:The composition of DHM differs from OMM and feeding of DHM has a significant impact on the metabolic phenotype and microbiota of preterm infants. Our data help to understand the origin of the observed changes generating new hypothesis: i) steroid hormones present in HM have a significant influence in the activity of the steroid hormone biosynthesis pathway in preterm infants; ii) the pyrimidine metabolism is modulated in preterm infants by the activity of gut-microbiota. Short-and longterm implications of the observed changes for preterm infants need to be assessed in further studies.

More evidence: Mothers’ own milk is personalized medicine for very low birthweight infants

“…The finding that high MOM intake was associated with significantly better outcomes joins two recent observational cohort studies of EHM-fed VLBW infants, 2 , 3 which compared health outcomes for predominantly MOM-fed versus predominantly PDHM-fed infants. Taken together, the three studies found that predominantly MOM-fed infants had better clinical outcomes, 1 , 3 healthier microbiome colonization 1 , 2 , 3 including potential modulation of the negative impact of antibiotic exposure, 1 , 3 and improved metabolic/metabolomic profiles 2 than primarily PDHM-fed infants. Furthermore, predominantly PDHM-fed infants had slower and/or impaired growth, 1 , 3 including higher rates of head circumference measures below the third percentile, 3 higher rates of bronchopulmonary dysplasia 3 , and altered pyrimidine and steroid pathways.…”

“…Furthermore, predominantly PDHM-fed infants had slower and/or impaired growth, 1 , 3 including higher rates of head circumference measures below the third percentile, 3 higher rates of bronchopulmonary dysplasia 3 , and altered pyrimidine and steroid pathways. 2 Although these studies were limited by relatively small sample sizes and observational designs, the convergence of findings adds to clinical concerns that high-dose PDHM may be an inadequate long-term supplement for low-dose MOM in VLBW infants. These findings have important implications for future research, clinical quality improvement initiatives, and efforts to prioritize the availability of MOM in the NICU.…”

“… 6 PDHM involves the reduction and/or eradication of MOM-borne digestive enzymes, MOM microbiota, and alterations in metabolic components and pathways. 1 , 2 , 3 , 6 Additionally, mothers who deliver preterm produce MOM that is higher in multiple bioactive components than PDHM from mothers of term infants, especially during the early weeks post-birth. 6 Many of these personalized medicine components target growth and may have a programming effect including growth factors, adipokines, micro RNAs, oligosaccharides, the MOM microbiome, the gut metabolome, and others.…”

From Intrauterine to Extrauterine Life—The Role of Endogenous and Exogenous Factors in the Regulation of the Intestinal Microbiota Community and Gut Maturation in Early Life

“…Preterm infants fed MOM show a significantly greater presence of Bifidobacteriaceae and a lower presence of Staphylococcaceae, Clostridiaceae, and Pasteurellaceae, compared to preterm infants fed DHM (67). Piñeiro-Ramos et al showed significant differences in the galactose, starch and sucrose metabolism pathways when comparing MOM and DHM, as well as differences in the gut microbiota composition (68). Moreover, it was shown that the protective effect of DHM is not complete probably due to destruction of the enzymes and immune molecules during pasteurization process (69,70).…”

When a Neonate Is Born, So Is a Microbiota

“…Throughout one’s life, microbiota can be influenced and modified by various factors, including maternal health [ 10 , 11 , 12 ], pregnancy complications, peripartum antibiotic administration [ 13 ], mode and place of delivery [ 14 ] and breastfeeding [ 11 , 15 , 16 , 17 , 18 , 19 , 20 ].…”