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Human milk oligosaccharide 2’-fucosyllactose and lacto-n-neo-tetraose attenuate early-weaning-induced intestinal barrier dysfunction via gut microbiota modulation in mice

ABSTRACT: Early weaning is a common practice among young mothers and is associated with an increased risk of gastrointestinal disorders. Human milk oligosaccharides (HMOs) play a critical role in maintaining gut barrier integrity and have been increasingly applied in infant formulas. However, the mechanisms of HMOs in maintaining gut function remain unclear. This study aimed to assess the effects of 2'-fucosyllactose (2'-FL) and Lacto-N-neotetraose (LNnT) in a mouse model of early weaning.

ORGANISM(S): Mus musculus

PROVIDER: GSE303393 | GEO | 2026/07/23

REPOSITORIES: GEO

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	GSE303393_1_genes_fpkm_expression.xlsx	Xlsx
	GSE303393_gene_count_matrix.xlsx	Xlsx

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Human Milk Oligosaccharide Utilization in Intestinal Bifidobacteria is Governed by Global Transcriptional Regulator NagR

Project description:Bifidobacterium longum subsp. infantis (B. infantis) is a prevalent beneficial bacterium that colonizes the human neonatal gut and is uniquely adapted to efficiently use human milk oligosaccharides (HMOs) as a carbon and energy source. Multiple studies have focused on characterizing the elements of HMO utilization machinery in B. infantis; however, the regulatory mechanisms governing the expression of these catabolic pathways remain poorly understood. A bioinformatic regulon reconstruction approach used in this study implicated NagR, a transcription factor from the ROK family, as a negative global regulator of genomic loci encoding lacto-N-biose/galacto-N-biose (LNB/GNB), lacto-N-tetraose (LNT), and lacto-N-neotetraose (LNnT) utilization pathways in B. infantis. This conjecture was corroborated by transcriptome profiling upon nagR genetic inactivation and experimental assessment of binding of recombinant NagR to predicted DNA operators. The latter approach also implicated N-acetylglucosamine (GlcNAc), a universal intermediate of LNT and LNnT catabolism, and its phosphorylated derivatives as plausible NagR effectors. Reconstruction of NagR regulons in various Bifidobacterium lineages revealed multiple regulon expansion events, suggesting evolution from a local regulator of GlcNAc catabolism in ancestral bifidobacteria to a global regulator controlling foraging of mixtures of GlcNAc-containing host-derived glycans in mammalian gut-colonizing B. infantis and Bifidobacterium bifidum.

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Strain-specific strategies of 2′-fucosyllactose, 3-fucosyllactose, and difucosyllactose assimilation by Bifidobacterium longum subsp. infantis Bi-26 and ATCC 15697

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Project description:The purpose of this project was to determine the whole transcriptome response of Bifidobacterium longum subsp. Infantis to pooled and individual human milk oligosaccharides (HMO) relative to lactose Bacterial isolates grown on lactose, pooled human milk oligosaccharides (HMO), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), 2âfucosyllactose (2âFL), 3-fucosyllactose (3FL), and 6âsialyllactose (6âSL). RNA was extracted and sequenced, in duplicate, on an Illumina HiSeq. Early, mid, and late timepoints in response to pooled HMO were additionally sequenced in duplicate.

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Project description:The purpose of this project was to determine the whole transcriptome response of Bifidobacterium bifidum SC555 to pooled and individual human milk oligosaccharides (HMO) relative to lactose Bacterial isolates grown on lactose, pooled human milk oligosaccharides (HMO), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), 2âfucosyllactose (2âFL), 3-fucosyllactose (3FL), 6âsialyllactose (6âSL) and porcine mucin (MUC). RNA was extracted and sequenced, in duplicate, on an Illumina HiSeq. Early, mid, and late timepoints in response to pooled HMO were additionally sequenced in duplicate.

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The human milk oligosaccharide 2’-fucosyllactose alleviates liver steatosis and associated gut permeability, ER stress and insulin resistance by reducing hepatic diacylglycerols in obese Ldlr-/-.Leiden mice

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2022-05-24 | GSE195862 | GEO

Bifidobacterium infantis metabolizes 2´fucosyllactose-derived and free fucose through a common catabolic pathway resulting in 1,2-propanediol secretion

Project description:Human milk oligosaccharides (HMOs) are highly diverse complex carbohydrates secreted in human milk. HMOs are indigestible by the infant and instead are metabolized by bifidobacteria in the infant gut microbiome to produce molecules that promote infant health and development. 2´fucosyllactose (2´FL) is an abundant HMO and is utilized by Bifidobacterium longum subsp. infantis, a predominant member of the infant gut microbiome. Currently, there is not a scientific consensus on how or if bifidobacteria metabolize the fucose portion of 2´FL or free fucose. This proteomic analysis was conducted in order to characterize the metabolic pathway by which B. infantis utilizes fucose.

2021-03-17 | PXD021868 | Pride

Novel Genes and Metabolite Trends in Bifidobacterium longum ssp. infantis Bi-26 Involved in Metabolism of Human Milk Oligosaccharide 2’-fucosyllactose

Project description:Human milk oligosaccharides (HMOs) function as prebiotics for beneficial bacteria in the developing gut, often dominated by Bifidobacterium spp. To understand the relationship between Bifidobacterium 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 ssp. 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 2’-FL metabolism is a complex process involving gene clusters throughout the genome producing more metabolites compared to lactose. These results provide valuable insight on the mode-of-action of 2’-FL utilization by Bifidobacterium longum ssp. infantis Bi-26.

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Bifidobacterium infantis metabolizes 2´fucosyllactose-derived and free fucose through a common catabolic pathway resulting in 1,2-propanediol secretion

Project description: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.

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