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Strain-Specific Strategies of Human Milk Oligosaccharide 2′-Fucosyllactose, 3-Fucosyllactose, and Difucosyllactose Assimilation by Bifidobacterium longum subsp. infantis Strains Bi-26 and ATCC 15697

ABSTRACT: Strain-Specific Strategies of Human Milk Oligosaccharide 2′-Fucosyllactose, 3-Fucosyllactose, and Difucosyllactose Assimilation by Bifidobacterium longum subsp. infantis Strains Bi-26 and ATCC 15697

PROVIDER: PRJNA637762 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11940507_1.fastq.gz	Fastqsanger.gz
	SRR11940507_2.fastq.gz	Fastqsanger.gz
	SRR11940508_1.fastq.gz	Fastqsanger.gz
	SRR11940508_2.fastq.gz	Fastqsanger.gz
	SRR11940509_1.fastq.gz	Fastqsanger.gz

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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

2020-06-07 | GSE151933 | GEO

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.

2019-04-23 | GSE122350 | 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) 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.

2020-10-08 | GSE159189 | GEO

Bifidobacterium longum subsp. infantis (B. infantis) strain dependent utilization of human milk oligosaccharides

Project description:Bifidobacterium longum subsp. infantis (B. infantis) colonizes the infant gut microbiome with a 43-kb gene cluster that enables human milk oligosaccharide (HMO) utilization. Although there is relative genomic homogeneity in this regard, previous observations suggest that B. infantis strains may differ in their utilization phenotype. To test this hypothesis, a panel of B. infantis strains were evaluated for their ability to utilize pooled HMOs to yield differential phenotypes including biomass accumulation, HMO consumption glycoprofile, end-product secretion, and global transcriptomes. Two strains (ATCC 15697 and UMA301) efficiently consumed several HMO isomers/anomers that exhibit degrees of polymerization (DP) ³ 4. These same strains partially consumed the smaller DP HMOs including fucosyllactose and lactodifucotetraose isomers/anomers. In contrast, UMA299 efficiently utilized fucosylated small molecular weight HMOs (DP<4), and accumulated greater biomass on purified 2´FL with significantly higher 1,2-propanediol production. This study identifies several strain-dependent features in HMO utilization phenotypes that are consistent with metabolic variation within a bifidobacterial-dominated infant-gut microbiome.

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

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

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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) 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

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

Project description:Abstract: - Non-alcoholic fatty liver disease (NAFLD) is a complex multifactorial disorder that is associated with gut dysbiosis, enhanced gut permeability, adiposity and insulin resistance. Prebiotics such as human milk oligosaccharide 2’-fucosyllactose are thought to primarily improve gut health and it is uncertain whether they would affect more distant organs. This study investigates whether 2’-fucosyllactose can alleviate NAFLD development in manifest obesity. Obese hyperinsulinemic Ldlr-/-.Leiden mice, after an 8 week run-in on HFD, were treated with 2’-fucosyllactose by oral gavage until week 28 and compared to HFD-vehicle controls. 2’-fucosyllactose did not affect food intake, body weight, total fat mass or plasma lipids. 2’-fucosyllactose altered the fecal microbiota composition which was paralleled by a suppression of HFD-induced gut permeability at t=12 weeks. 2’-fucosyllactose significantly attenuated the development of NAFLD by reducing microvesicular steatosis. These hepatoprotective effects were supported by functional transcriptome analyses showing that 2’-fucosyllactose activated ACOX1 (involved in lipid catabolism), while deactivating SREBF1 (involved in lipogenesis). Furthermore, 2’-fucosyllactose suppressed ATF4, ATF6, ERN1, and NUPR1 all of which participate in ER stress. 2’-fucosyllactose reduced fasting insulin concentrations and HOMA-IR, which was corroborated by decreased intrahepatic diacylglycerols. - In conclusion, long-term prebiotic treatment with 2’-fucosyllactose can counteract the detrimental effects of HFD on gut dysbiosis and gut permeability and attenuates the development of liver steatosis. The observed reduction in intrahepatic diacylglycerols provides a mechanistic rationale for the improvement of hyperinsulinemia and supports the use of 2’-fucosyllactose to correct dysmetabolism and insulin resistance.

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RNA sequencing of Bifidobacterium longum subsp. infantis in response to various substrates

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.

2015-10-28 | E-GEOD-58773 | biostudies-arrayexpress

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

Project description:Human milk provides essential nutrients for infant nutrition. A large proportion of human milk is composed of human milk oligosaccharides (HMOs), which are resistant to digestion by the infant. Instead, HMOs act as a bioactive and prebiotic enriching HMO-utilizing bacteria and cause systematic changes in the host. Several species of Bifidobacterium have been shown to utilize HMOs by conserved, as well as species-specific pathways, but less work has been done to study variation within species or sub-species. B. longum subsp. infantis is a prevalent species in the breast-fed infant gut and the molecular mechanisms of HMO utilization for the type strain B. longum subsp. infantis ATCC 15697 (type strain) have been well characterized. We used growth, transcriptomic, and metabolite analysis to characterize key differences in the utilization of 2'FL, 3FL and DFL (FLs) between B. longum subsp. infantis Bi-26 (Bi-26) and the type strain. Bi-26 grows faster, produces unique metabolites, and has a distinct global gene transcription response to FLs compared to the type strain. Taken together the findings demonstrate major strain specific adaptations in Bi-26 to efficient utilization of FLs.

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