Breast milk urea as a nitrogen source for urease positiveBifidobacterium infantis

Abstract

Human milk stimulates a health-promoting gut microbiome in infants. However, it is unclear how the microbiota salvages and processes its required nitrogen from breast milk. Human milk nitrogen sources such as urea could contribute to the composition of this early life microbiome. Urea is abundant in human milk, representing a large part of the non-protein nitrogen (NPN). We found that B. longum subsp. infantis (ATCC17930) can use urea as a main source of nitrogen for growth in synthetic medium and enzyme activity was induced by the presence of urea in the medium. We furthermore confirmed the expression of both urease protein subunits and accessory proteins of B. longum subsp. infantis through proteomics. To the same end, metagenome data were mined for urease-related genes. It was found that the breastfed infant's microbiome possessed more urease-related genes than formula fed infants (51.4:22.1; 2.3-fold increase). Bifidobacteria provided a total of 106 of urease subunit alpha alignments, found only in breastfed infants. These experiments show how an important gut commensal that colonizes the infant intestine can metabolise urea. The results presented herein further indicate how dietary nitrogen can determine bacterial metabolism in the neonate gut and shape the overall microbiome.

StrainPanDA: linked reconstruction of strain composition and gene content profiles via pangenome-based decomposition of metagenomic data

“…In addition, the urease-related gene families were only found in the gene family profile of subspecies 1. Therefore, the unique functional potential of B. longum subspecies 1 in utilizing HMO and urea 51 from breast milk could confer a fitness advantage under breastfeeding, consistent with our observations of its transient dominance at 4 months in infant gut metagenomes.…”

“…For functional interpretation of the subspecies, we grouped the gene families annotated to the same KEGG ortholog or CAZy family. To further analyze the key functions related to breastfeeding, we curated a set of KEGG orthologs from related references 51,79 . All the KEGG orthologs were further grouped into subclasses and classes based on the literature 51,79 ( Supplementary Table 7 ).…”

“…To further analyze the key functions related to breastfeeding, we curated a set of KEGG orthologs from related references 51,79 . All the KEGG orthologs were further grouped into subclasses and classes based on the literature 51,79 ( Supplementary Table 7 ). The gene family coverage was calculated as the fraction of detected genes belonging to the subclass ( Fig.…”

StrainPanDA: Linked reconstruction of strain composition and gene content profiles via pangenome‐based decomposition of metagenomic data

“…In addition, the urease-related gene families were only found in the gene family profile of subspecies 1. Therefore, the unique functional potential of B. longum subspecies 1 in utilizing HMO and urea [51] from breast milk could confer a competitive advantage under breastfeeding, consistent with our observations of its transient dominance at 4 months in infant gut metagenomes.…”

Urine Metabolomic Profile of Breast- versus Formula-Fed Neonates Using a Synbiotic-Enriched Formula

“…Urea is considered the most important source of nitrogen, and its presence in the urine metabolome of newborns is anticipated. A strong correlation of urea with the BF group was closely associated with the modification of their intestinal microbiome and the increase in commensal bacterial populations, such as Bifidobacteria [ 60 ]. Nonetheless, in the case of the FF group, the consistent intake of protein-enriched infant formula for a certain period of time (3 months in our study) normally leads to increased levels of nitrogen metabolites, such as urea and creatine, which are related to the protein degradation pathways ( Figure 5 ) [ 42 , 61 , 62 ].…”