Nursing our microbiota: molecular linkages between bifidobacteria and milk oligosaccharides

Abstract

As the sole nutrition provided to infants, bioactive molecules dissolved in milk influence the development of our gut microbiota. Accordingly, human milk oligosaccharides (HMOs) are minimally digested by the infant and persist to negatively and positively regulate gut microbiota. Infant-type bifidobacteria utilize these soluble carbohydrate oligomers by convergent mechanisms. Bifidobacterium longum subsp. infantis efficiently consumes several small mass HMOs and possesses a large gene cluster and other loci dedicated to HMO metabolism. In contrast, adult-associated bifidobacteria such as the closely related B. longum subsp. longum are deficient for HMO utilization, although they retain the capacity to ferment plant oligosaccharides and constituent pentose sugars. Thus, the ability to subsist on HMO could demark infant-associated ecotypes potentially adapted to colonize the nursing infant.

Figure 1

Basic structures of human milk oligosaccharides and glycan mimetics. HMO possesses much more structural variability in monosaccharide constituents and linkages compared to fructo-oligosaccharides and galacto-oligosaccharides.

Figure 2

Percent of COG genes assigned carbohydrate processing function in Bifidobacterium and Bacteroides. The phyla Actinobacteria and Bacteroidetes have approximately equivalent percentages of carbohydrate transport and metabolism COG category G proteins, while these are enriched in member genera Bifidobacterium and Bacteroides. Bifidobacterium are enriched for transport-related COGs while Bacteroides possesses an abundance of glycosyl hydrolases.

Figure 3

Putative modes of accessing milk glycans in the infant gut by bifidobacteria. B. longum subsp. infantis captures intact HMO, while B. bifidum secretes extracellular enzymes prior to translocating lacto-N-biose degradation products. B. breve utilizes HMO monosaccharides cleaved by extracellular enzymes secreted by heterologous members of the consortium.

Figure 4

Phenotypic variation of HMO utilization in bifidobacteria. The consumption of HMO as a sole carbon source data is derived from Ref. [24], and the relative abundances were originally presented in Ref. [54]. Abbreviations: LNT, Lacto-N-tetraose-like.

Figure 5

Endo-galactanase locus in B. longum subsp. longum NCC2705 and variations in other bifidobacteria. The gene cluster is conserved in B. adolescentis ATCC15703 with the exception of the endo-galactanase. The closely related B. longum subsp. infantis ATCC15697 is missing or possesses degraded homologs of this cluster. Gene fragments are denoted in smaller text below the genes. The locus number for the fadD1 gene is listed above. Abbreviations: sbp1, solute binding protein family 1; β-gal, β-galactosidase; endo -gal, endo-galactosidase; hyp, hypothetical protein; dh, dehydrogenase; HK, histidine kinase; RR, response regulator; cin, bacteriocin; tr, transport related; fadD1, long-chain acyl-CoA synthetase; pdxS, pyridoxine biosynthesis gene; pdxT, glutamine amidotransferase; lacI, lacI family transcriptional regulator; cysN, sulfate adenylyltransferase subunit 1.