Preterm Gut Microbiome Depending on Feeding Type: Significance of Donor Human Milk

Abstract

Preterm microbial colonization is affected by gestational age, antibiotic treatment, type of birth, but also by type of feeding. Breast milk has been acknowledged as the gold standard for human nutrition. In preterm infants breast milk has been associated with improved growth and cognitive development and a reduced risk of necrotizing enterocolitis and late onset sepsis. In the absence of their mother’s own milk (MOM), pasteurized donor human milk (DHM) could be the best available alternative due to its similarity to the former. However, little is known about the effect of DHM upon preterm microbiota and potential biological implications. Our objective was to determine the impact of DHM upon preterm gut microbiota admitted in a referral neonatal intensive care unit (NICU). A prospective observational cohort study in NICU of 69 neonates <32 weeks of gestation and with a birth weight ≤1,500 g was conducted. Neonates were classified in three groups according to feeding practices consisting in their MOM, DHM, or formula. Fecal samples were collected when full enteral feeding (defined as ≥150 cc/kg/day) was achieved. Gut microbiota composition was analyzed by 16S rRNA gene sequencing. Despite the higher variability, no differences in microbial diversity and richness were found, although feeding type significantly influenced the preterm microbiota composition and predictive functional profiles. Preterm infants fed MOM showed a significant greater presence of Bifidobacteriaceae and lower of Staphylococcaceae, Clostridiaceae, and Pasteurellaceae compared to preterm fed DHM. Formula fed microbial profile was different to those observed in preterm fed MOM. Remarkably, preterm infants fed DHM showed closer microbial profiles to preterm fed their MOM. Inferred metagenomic analyses showed higher presence of Bifidobacterium genus in mother’s milk group was related to enrichment in the Glycan biosynthesis and metabolism pathway that was not identified in the DHM or in the formula fed groups. In conclusion, DHM favors an intestinal microbiome more similar to MOM than formula despite the differences between MOM and DHM. This may have potential beneficial long-term effects on intestinal functionality, immune system, and metabolic activities.

Antibiotics and the developing intestinal microbiome, metabolome and inflammatory environment: a randomized trial of preterm infants

“…Our results confirm that feeding type also have a significant influence on gut microbiome richness, diversity and bacterial load 31–33 . Exclusive or partial feeding with mother’s own milk tended to associate with high bacterial load, which is supported by evidence that breast milk harbors maternal-originating bacteria, as well as nutritional components (prebiotics) that support bacterial proliferation in the intestinal tract 34,35 .…”

Inherited nongenetic influences on the gut microbiome and immune system

“…The World Health Organization Global Breastfeeding Collective current initiative is to promote breastfeeding within an hour of a child's birth and exclusive breastfeeding for the first 6 months of life (Grummer‐Strawn et al, ; Khan, Vesel, Bahl, & Martines, ). As this is not always possible for multiple reasons, physiological and emotional, use of donor milk through milk banks, have become a popular diet choice compared to infant formula (Chen, ; Parra‐Llorca et al, ). Although the biologically active proteins reviewed above can be destroyed during the pasteurization process (Reeves, Johnson, Vasquez, Maheshwari, & Blanco, ; Untalan, Keeney, Palkowetz, Rivera, & Goldman, ), increasingly neonatal intensive care units have begun providing donor milk in an effort to provide complete nutrition and protection to premature infants (Adhisivam et al, ).…”

“…Although the biologically active proteins reviewed above can be destroyed during the pasteurization process (Reeves, Johnson, Vasquez, Maheshwari, & Blanco, ; Untalan, Keeney, Palkowetz, Rivera, & Goldman, ), increasingly neonatal intensive care units have begun providing donor milk in an effort to provide complete nutrition and protection to premature infants (Adhisivam et al, ). Preterm infants fed donor milk had gut microbiomes that more closely resembled infants fed their mother's own milk compared with formula fed infants (Parra‐Llorca et al, ). In addition, some groups have tested the viability of “spiking” donor milk with infants' own mothers milk to inoculate the infants with a personalized microbiome (Cacho et al, ), a concept similar to a recent push to include probiotics in infant formula (Aceti et al, ; Cavallaro, Villamor‐Martínez, Filippi, Mosca, & Villamor, ; Mugambi, Musekiwa, Lombard, Young, & Blaauw, ; Rautava et al, ; Villamor‐Martínez et al, ).…”

Uncovering microbial populations in the lumen of neonatal enteral feeding tubes utilising 16s rRNA sequencing

“…Many of these effects may also be mediated through alterations in intestinal bacterial flora. Whilst MBM is beneficial, it is not always available and so alternative feeds must be utilised; with many studies demonstrating that these alternative feeds can impact microbiome development 18 19 . Feed type therefore clearly has implications for microbiome development and outcomes in preterm infants.…”