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The HMO 2’-fucosyllactose alone and in combination with resistant starch increase circulating short-chain fatty acid in lean men and in men with prediabetes and obesity

ABSTRACT: The effects of 2’-fucosyllactose on acetate production

PROVIDER: PRJEB57807 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR11668500_1.fastq.gz	Fastqsanger.gz
	ERR11668500_2.fastq.gz	Fastqsanger.gz
	ERR11668501_1.fastq.gz	Fastqsanger.gz
	ERR11668501_2.fastq.gz	Fastqsanger.gz
	ERR11668502_1.fastq.gz	Fastqsanger.gz

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2'-fucosyllactose alone or combined with resistant starch increases circulating short-chain fatty acids in lean men and men with prediabetes and obesity.

Project description:BackgroundInfusion of short-chain fatty acids (SCFA) to the distal colon beneficially affects human substrate and energy metabolism. Here, we hypothesized that the combination of 2'-fucosyllactose (2'-FL) with resistant starch (RS) increases distal colonic SCFA production and improves metabolic parameters.MethodsIn this randomized, crossover study, 10 lean (BMI 20-24.9 kg/m2) and nine men with prediabetes and overweight/obesity (BMI 25-35 kg/m2) were supplemented with either 2'-FL, 2'-FL+RS, or placebo one day before a clinical investigation day (CID). During the CID, blood samples were collected after a overnight fast and after intake of a liquid high-fat mixed meal to determine plasma SCFA (primary outcomes). Secondary outcomes were fasting and postprandial plasma insulin, glucose, free fatty acid (FFA), glucagon-like peptide-1, and peptide YY concentrations. In addition, fecal SCFA and microbiota composition, energy expenditure and substrate oxidation (indirect calorimetry), and breath hydrogen excretion were determined.ResultsIn lean men, supplementation with 2'-FL increased postprandial plasma acetate (P = 0.017) and fasting H2 excretion (P = 0.041) compared to placebo. Postprandial plasma butyrate concentration increased after 2'-FL and 2'-FL+RS as compared to placebo (P < 0.05) in lean men and men with prediabetes and overweight/obesity. Additionally, 2'-FL+RS decreased fasting and postprandial plasma FFA concentrations compared to placebo (P < 0.05) in lean men.ConclusionSupplementation of 2'-FL with/without RS the day before investigation increased systemic butyrate concentrations in lean men as well as in men with prediabetes and obesity, while acetate only increased in lean men. The combination of 2'-FL with RS showed a putatively beneficial metabolic effect by lowering plasma FFA in lean men, indicating a phenotype-specific effect.Clinical trial registrationnr. NCT04795804.

| S-EPMC10388544 | biostudies-literature

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

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.

2022-05-24 | GSE195862 | GEO

Bifidobacterium kashiwanohense expresses fucosidases necessary for fucosyllactose utilisation as an adaptation to the infant gut environment

Project description:Bifidobacteria dominate the composition of the neonatal gut microbiota in the first number of weeks following birth. A number of species in particular are found with a significantly higher frequency in the microbiome of breastfed infants, owing to their ability to rely on Human Milk Oligosacchraides (HMOs) as their sole carbohydrate substrate; namely B. bifidum, B. longum spp. infantis and B. breve. Bifidobacterium kashiwanohense is a species that has been isolated previously only from the faeces of infants, but extremely infrequently at that. Relatively little is currently known about the species itself, let alone the metabolic pathways that allow it to successfully establish a population in the infant gut. We have isolated a novel strain of B. kashiwanohense from the faeces of a breastfed infant on the basis of its ability to utilise the HMO component fucosyllactose as its sole carbohydrate source. In this study, we read and annotate the full genome sequence of this novel strain, and use the data obtained to direct our further experimental analysis of fucosyllactose metabolism in B. kashiwanohense. Using transcriptomic and growth analysis results, we identify the genes responsible for B. kashiwanohense to utilise fucosyllactose, and employ a combination of cloning, in vitro hydrolysis assays, and further, recombinant transcriptomic and growth assays to elucidate the pathway for fucosyllactose metabolism in B. kashiwanohense, as well as revealing insight into fucosyllactose and fucose metabolism in Bifidobacteria as whole.

2019-11-12 | GSE107439 | 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

Short-Term Cooling Increases Plasma ANGPTL3 and ANGPTL8 in Young Healthy Lean Men but Not in Middle-Aged Men with Overweight and Prediabetes.

Project description:Angiopoietin-like proteins (ANGPTLs) regulate triglyceride (TG)-rich lipoprotein distribution via inhibiting TG hydrolysis by lipoprotein lipase in metabolic tissues. Brown adipose tissue combusts TG-derived fatty acids to enhance thermogenesis during cold exposure. It has been shown that cold exposure regulates ANGPTL4, but its effects on ANGPTL3 and ANGPTL8 in humans have not been elucidated. We therefore investigated the effect of short-term cooling on plasma ANGPTL3 and ANGPTL8, besides ANGPTL4. Twenty-four young, healthy, lean men and 20 middle-aged men with overweight and prediabetes were subjected to 2 h of mild cooling just above their individual shivering threshold. Before and after short-term cooling, plasma ANGPTL3, ANGPTL4, and ANGPTL8 were determined by ELISA. In young, healthy, lean men, short-term cooling increased plasma ANGPTL3 (+16%, p < 0.05), ANGPTL4 (+15%, p < 0.05), and ANGPTL8 levels (+28%, p < 0.001). In middle-aged men with overweight and prediabetes, short-term cooling only significantly increased plasma ANGPTL4 levels (+15%, p < 0.05), but not ANGPTL3 (230 ± 9 vs. 251 ± 13 ng/mL, p = 0.051) or ANGPTL8 (2.2 ± 0.5 vs. 2.3 ± 0.5 μg/mL, p = 0.46). We show that short-term cooling increases plasma ANGPTL4 levels in men, regardless of age and metabolic status, but only overtly increases ANGPTL3 and ANGPTL8 levels in young, healthy, lean men.

| S-EPMC6723119 | biostudies-literature

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

Project description: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

| PRJNA637762 | ENA

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

Dietary Oligofructose Alone or in Combination with 2'-Fucosyllactose Differentially Improves Recognition Memory and Hippocampal mRNA Expression.

Project description:Mounting evidence suggests that dietary oligosaccharides promote brain development. This study assessed the capacity of oligofructose (OF) alone or in combination with 2'-fucosyllactose (2'-FL) to alter recognition memory, structural brain development, and hippocampal gene expression. Beginning on postnatal day (PND) 2, male pigs received one of three milk replacers formulated to contain OF, OF + 2'-FL, or no oligosaccharides (CON). Pigs were tested on the novel object recognition task using delays of 1 or 48 h at PND 22. At PND 32-33, magnetic resonance imaging (MRI) procedures were used to assess structural brain development and hippocampal tissue was collected for analysis of mRNA expression. Pigs that consumed the OF diet demonstrated increased recognition memory after a 1 h delay, whereas those consuming diets containing OF + 2'-FL displayed increased recognition memory after a 48 h delay. Pigs fed OF or OF + 2'-FL exhibited a larger relative volume of the olfactory bulbs compared with CON pigs. Provision of OF or OF + 2'-FL altered gene expression related to dopaminergic, GABAergic, cholinergic, cell adhesion, and chromatin remodeling processes. Collectively, these data indicate that dietary OF and OF + 2'-FL differentially improve cognitive performance and affect olfactory bulb structural development and hippocampal gene expression.

| S-EPMC7400822 | biostudies-literature

The human milk oligosaccharide 2’-fucosyllactose protects against high-fat diet induced obesity by changing intestinal mucus production, composition and degradation linked to changes in gut microbiota and fecal proteome profiles in mice

Project description:The aim of this study was to decipher the mechanisms by which the major human milk oligosaccharide (HMO), 2’-fucosyllactose (2’FL), can affect body weight and fat mass gain upon high-fat diet (HFD) feeding in mice. In particular, we wanted to elucidate whether 2’FL metabolic effects are linked with changes in intestinal mucus production and secretion, mucin glycosylation and degradation, as well as with the modulation of the gut microbiota, fecal proteome and endocannabinoid (eCB) system.

2025-05-06 | PXD049406 | Pride

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