Abstract
Human milk contains a high concentration of indigestible oligosaccharides, which likely mediated the coevolution of the nursing infant with its gut microbiome. Specifically, Bifidobacterium longum subsp. infantis (B. infantis) often colonizes the infant gut and utilizes these human milk oligosaccharides (HMOs) to enrich their abundance. In this study, the physiology and mechanisms underlying B. infantis utilization of two HMO isomers lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT) was investigated in addition to their carbohydrate constituents. Both LNT and LNnT utilization induced a significant shift in the ratio of secreted acetate to lactate (1.7–2.0) in contrast to the catabolism of their component carbohydrates (~1.5). Inefficient metabolism of LNnT prompts B. infantis to shunt carbon toward formic acid and ethanol secretion. The global transcriptome presents genomic features differentially expressed to catabolize these two HMO species that vary by a single glycosidic linkage. Furthermore, a measure of strain-level variation exists between B. infantis isolates. Regardless of strain, inefficient HMO metabolism induces the metabolic shift toward formic acid and ethanol production. Furthermore, bifidobacterial metabolites reduced LPS-induced inflammation in a cell culture model. Thus, differential metabolism of milk glycans potentially drives the emergent physiology of host-microbial interactions to impact infant health.
Highlights
Breastfeeding is critical for infant development and health in the absence of formula milk substitutes
In order to understand B. infantis metabolism of Human milk oligosaccharides (HMOs), the type strain ATCC 15697 was subjected to growth on purified HMO species and constituent mono- and di-saccharides
Bifidobacterium longum subsp. infantis evolved to utilize glycans secreted in human milk to generate ATP as well as provide substrates for anabolic processes
Summary
Breastfeeding is critical for infant development and health in the absence of formula milk substitutes. Bifidobacterium infantis Metabolism of Human Milk Tetrasaccharides of five monosaccharides: D-glucose (Glc), D-galactose (Gal), N-acetylglucosamine (GlcNAc), L-fucose (Fuc), and N-acetylneuraminic acid (Neu5Ac or sialic acid) with a varying degree of polymerization and branching [6,7,8,9] These oligosaccharides are not directly metabolized by the infant; commensal bifidobacteria have coevolved within the nursing infant gut to utilize HMO [10, 11]. It is likely that B. infantis catabolizes HMO-derived monosaccharides through the F6PPK pathway to generate ATP [26] This potentially links bifidobacterial physiology (i.e., flux through the F6PPK pathway) with infant nutritional and health outcomes as B. infantis benefits their developing host [27, 28]
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