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. 2024 Sep 17;5(9):101708.
doi: 10.1016/j.xcrm.2024.101708. Epub 2024 Aug 30.

Human milk microbiota, oligosaccharide profiles, and infant gut microbiome in preterm infants diagnosed with necrotizing enterocolitis

Andrea C Masi  1 , Lauren C Beck  1 , John D Perry  2 , Claire L Granger  3 , Alice Hiorns  1 , Gregory R Young  4 , Lars Bode  5 , Nicholas D Embleton  6 , Janet E Berrington  7 , Christopher J Stewart  8
Affiliations

Human milk microbiota, oligosaccharide profiles, and infant gut microbiome in preterm infants diagnosed with necrotizing enterocolitis

Andrea C Masi et al. Cell Rep Med. .

Abstract

Necrotizing enterocolitis (NEC) is a severe intestinal disease of very preterm infants with mother's own milk (MOM) providing protection, but the contribution of the MOM microbiota to NEC risk has not been explored. Here, we analyze MOM of 110 preterm infants (48 NEC, 62 control) in a cross-sectional study. Breast milk contains viable bacteria, but there is no significant difference in MOM microbiota between NEC and controls. Integrative analysis between MOM microbiota, human milk oligosaccharides (HMOs), and the infant gut microbiota shows positive correlations only between Acinetobacter in the infant gut and Acinetobacter and Staphylococcus in MOM. This study suggests that NEC protection from MOM is not modulated through the MOM microbiota. Thus, "'restoring" the MOM microbiota in donor human milk is unlikely to reduce NEC, and emphasis should instead focus on increasing fresh maternal human milk intake and researching different therapies for NEC prevention.

Keywords: gut microbiome; infant microbiome; microbiota; milk microbiome; multi-omics; necrotizing enterocolitis; preterm infant.

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Conflict of interest statement

Declaration of interests L.B. is the UC San Diego Chair of Collaborative Human Milk Research, endowed by the Family Larsson-Rosenquist Foundation (FLRF), Switzerland. L.B. is a co-inventor on patent applications related to the use of HMOs in preventing NEC and other inflammatory diseases. N.D.E. and J.E.B. report grants to their institutions from Prolacta Bioscience US and Danone Early Life Nutrition. N.D.E. declares lecture honoraria donated to charity from Nestlé Nutrition Institute. C.J.S. declares lecture honoraria from Nestlé Nutrition Institute.

Figures

None
Graphical abstract
Figure 1
Figure 1
Cross-sectional overview of the MOM microbiota in preterm infants (A) Boxplots showing the alpha diversity based on observed OTUs (operational taxonomic unit; richness) and Shannon diversity. Boxplots showing the relative abundance of phyla (B) and the top 10 most abundant genera (C); square-root scaling was applied to the y axis. (D) Boxplot of the total bacterial load; log10 scaling was applied to the y axis. A total 110 preterm infants were included.
Figure 2
Figure 2
Analysis of mother’s own milk microbiota from preterm infants who were diagnosed with NEC and matched controls (A) Boxplots showing the alpha diversity based on observed OTUs (richness) and Shannon diversity. p values were calculated by applying the Mann-Whitney test and adjusted using the false discovery rate (FDR) algorithm. (B–D) (B) NMDS plot of weighted Bray-Curtis dissimilarity. p value based on permutational analysis of variance (PERMANOVA). Boxplots showing the relative abundance of phyla (C) and the top 10 most abundant genera (D); square-root scaling was applied to the y axis. (E) Boxplot of the total bacterial load; log10 scaling was applied to the y axis; p = 0.33. p values were calculated by applying the Mann-Whitney test and adjusted using the FDR algorithm. Adjusted p values in (C) and (D) were all >0.05. A total of 62 control and 48 NEC infants were included. See also Figures S1–S3.
Figure 3
Figure 3
Correlation plots between the relative abundance of genera in the infant gut and mother’s own milk (A) Regression plot of MOM Staphylococcus relative abundance (RelAb) and infant Acinetobacter RelAb, p < 0.01. (B) MOM Acinetobacter RelAb and infant Acinetobacter RelAb, p < 0.01. (C) MOM Acinetobacter RelAb and MOM Staphylococcus RelAb, p < 0.001. For each panel, square-root scaling was applied to the y axis. R and p values were calculated by Spearman correlation analysis, and all p values were adjusted using the FDR algorithm. A total of 54 preterm infants were included.
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