Abstract
Human milk oligosaccharides (HMOs) function as prebiotics for beneficial bacteria in the developing gut, often dominated by Bifidobacterium spp. To understand the relationship between bifidobacteria utilizing HMOs and how the metabolites that are produced could affect the host, we analyzed the metabolism of HMO 2′-fucosyllactose (2′-FL) in Bifidobacterium longum subsp. infantis Bi-26. RNA-seq and metabolite analysis (NMR/GCMS) was performed on samples at early (A600 = 0.25), mid-log (0.5–0.7) and late-log phases (1.0–2.0) of growth. Transcriptomic analysis revealed many gene clusters including three novel ABC-type sugar transport clusters to be upregulated in Bi-26 involved in processing of 2′-FL along with metabolism of its monomers glucose, fucose and galactose. Metabolite data confirmed the production of formate, acetate, 1,2-propanediol, lactate and cleaving of fucose from 2′-FL. The formation of acetate, formate, and lactate showed how the cell uses metabolites during fermentation to produce higher levels of ATP (mid-log compared to other stages) or generate cofactors to balance redox. We concluded that 2′-FL metabolism is a complex process involving multiple gene clusters, that produce a more diverse metabolite profile compared to lactose. These results provide valuable insight on the mode-of-action of 2′-FL utilization by Bifidobacterium longum subsp. infantis Bi-26.
Highlights
A large proportion of ingested human milk oligosaccharides (HMOs) reach the large intestine in an intact form and act as prebiotics by providing a metabolic substrate for the growth and activity of potentially beneficial gut bacteria, such as Bifidobacterium species[1,2,3]
The assembly resulted in a weighted median contig statistic (N50) score of 143,137 with the smallest number of contigs whose length sum produces N50 (L50) score of 6
The genome contains the necessary enzymes to breakdown 2′-FL into its monomers along with the Leloir pathway, fucose, and central metabolism genes to potentially process the monomers into 1,2-propanediol (1,2-PD), lactate and acetate as described in Supplementary Table 2 17,18
Summary
A large proportion of ingested human milk oligosaccharides (HMOs) reach the large intestine in an intact form and act as prebiotics by providing a metabolic substrate for the growth and activity of potentially beneficial gut bacteria, such as Bifidobacterium species[1,2,3]. HMOs are the third most abundant solid component in human milk after lactose and lipids[7]. They consist of more than 200 structurally diverse carbohydrate polymers that are composed of five monomers: D-glucose, D-galactose, N-acetylglucosamine, L-fucose and N-acetylneuraminic acid (sialic acid). Pathways of HMO metabolism have previously been explored genomically and by comparative transcriptomics in infant-associated Bifidobacterium species[14,15,16]. Through transcriptomic and metabolite analysis we can better understand the utilization of 2′-FL by B. longum subsp. infantis Bi-26 strain, and demonstrate the potential synergistic function of this HMO-probiotic combination
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