Abstract
Human milk oligosaccharides (HMOs) enrich beneficial bifidobacteria in the infant gut microbiome which produce molecules that impact development and physiology. 2′fucosyllactose (2′FL) is a highly abundant fucosylated HMO which is utilized by Bifidobacterium longum subsp. infantis, despite limited scientific understanding of the underlying mechanism. Moreover, there is not a current consensus on whether free fucose could be metabolized when not incorporated in a larger oligosaccharide structure. Based on metabolic and genomic analyses, we hypothesize that B. infantis catabolizes both free fucose and fucosyl oligosaccharide residues to produce 1,2-propanediol (1,2-PD). Accordingly, systems-level approaches including transcriptomics and proteomics support this metabolic path. Co-fermentation of fucose and limiting lactose or glucose was found to promote significantly higher biomass and 1,2-PD concentrations than individual substrates, suggesting a synergistic effect. In addition, and during growth on 2′FL, B. infantis achieves significantly higher biomass corresponding to increased 1,2-PD. These findings support a singular fucose catabolic pathway in B. infantis that is active on both free and HMO-derived fucose and intimately linked with central metabolism. The impact of fucose and 2′FL metabolism on B. infantis physiology provides insight into the role of fucosylated HMOs in influencing host- and microbe-microbe interactions within the infant gut microbiome.
Highlights
Human milk nourishes infants and contains host-indigestible human milk oligosaccharides (HMOs) in addition to bioavailable nutrients
This study investigates B. infantis utilization of 2′FL-derived and free fucose as well as the impact of carbohydrate source and concentration on fucose metabolism
In order to understand B. infantis metabolism of free fucose and Human milk oligosaccharides (HMOs)-derived fucose, B. infantis ATCC 15697 was subjected to growth on fucose as a sole carbohydrate source and in cofermentation with other sugars
Summary
Human milk nourishes infants and contains host-indigestible human milk oligosaccharides (HMOs) in addition to bioavailable nutrients These compounds contribute to overall infant nutrition by shifting gut microbiome composition to favor beneficial microbiota that metabolize HMOs to bioactive products [1,2,3,4,5]. B. infantis lacks the full complement of the canonical pathway genes possessed by other bacteria such as Escherichia coli [12,13,14]. This catabolic pathway results in the production of 1,2-propanediol (1,2-PD) through a series of phosphorylated intermediates [15, 16]. B. infantis has been previously observed to metabolize free fucose and produces 1,2-PD in cofermentation with a low concentration of glucose [14]
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