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Potential roles of 1,5-anhydro-D-fructose in modulating gut microbiome in mice.

ABSTRACT: The gut microbiota has tremendous potential to affect the host's health, in part by synthesizing vitamins and generating nutrients from food that is otherwise indigestible by the host. 1,5-Anhydro-D-fructose (1,5-AF) is a monosaccharide with a wide range of bioactive potentials, including anti-oxidant, anti-inflammatory, and anti-microbial effects. Based on its potential benefits and minimal toxicity, it is anticipated that 1,5-AF will be used as a dietary supplement to support general health. However, the effects of 1,5-AF on the gut microbiota are yet to be clarified. Here, using an unbiased metagenomic approach, we profiled the bacterial taxa and functional genes in the caecal microbiota of mice fed a diet containing either 2% 1,5-AF or a reference sweetener. Supplementation with 1,5-AF altered the composition of the gut microbiota, enriching the proportion of Faecalibacterium prausnitzii. 1,5-AF also altered the metabolomic profile of the gut microbiota, enriching genes associated with nicotinamide adenine dinucleotide biosynthesis. These findings support the potential benefits of 1,5-AF, but further studies are required to clarify the impact of 1,5-AF on health and disease.

SUBMITTER: Ito T

PROVIDER: S-EPMC8490373 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Catabolism of 1,5-anhydro-D-fructose in Sinorhizobium morelense S-30.7.5: discovery, characterization, and overexpression of a new 1,5-anhydro-D-fructose reductase and its application in sugar analysis and rare sugar synthesis.

Project description:The bacterium Sinorhizobium morelense S-30.7.5 was isolated by a microbial screening using the sugar 1,5-anhydro-D-fructose (AF) as the sole carbon source. This strain metabolized AF by a novel pathway involving its reduction to 1,5-anhydro-D-mannitol (AM) and the further conversion of AM to D-mannose by C-1 oxygenation. Growth studies showed that the AF metabolizing capability is not confined to S. morelense S-30.7.5 but is a more common feature among the Rhizobiaceae. The AF reducing enzyme was purified and characterized as a new NADPH-dependent monomeric reductase (AFR, EC 1.1.1.-) of 35.1 kDa. It catalyzed the stereoselective reduction of AF to AM and also the conversion of a number of 2-keto aldoses (osones) to the corresponding manno-configurated aldoses. In contrast, common aldoses and ketoses, as well as nonsugar aldehydes and ketones, were not reduced. A database search using the N-terminal AFR sequence retrieved a putative 35-kDa oxidoreductase encoded by the open reading frame Smc04400 localized on the chromosome of Sinorhizobium meliloti 1021. Based on sequence information for this locus, the afr gene was cloned from S. morelense S-30.7.5 and overexpressed in Escherichia coli. In addition to the oxidoreductase of S. meliloti 1021, AFR showed high sequence similarities to putative oxidoreductases of Mesorhizobium loti, Brucella suis, and B. melitensis but not to any oxidoreductase with known functions. AFR could be assigned to the GFO/IDH/MocA family on the basis of highly conserved common structural features. His6-tagged AFR was used to demonstrate the utility of this enzyme for AF analysis and synthesis of AM, as well as related derivatives.

| S-EPMC1392929 | biostudies-literature

1,5-Anhydro-D-fructose Protects against Rotenone-Induced Neuronal Damage In Vitro through Mitochondrial Biogenesis.

Project description:Mitochondrial functional abnormalities or quantitative decreases are considered to be one of the most plausible pathogenic mechanisms of Parkinson's disease (PD). Thus, mitochondrial complex inhibitors are often used for the development of experimental PD. In this study, we used rotenone to create in vitro cell models of PD, then used these models to investigate the effects of 1,5-anhydro-D-fructose (1,5-AF), a monosaccharide with protective effects against a range of cytotoxic substances. Subsequently, we investigated the possible mechanisms of these protective effects in PC12 cells. The protection of 1,5-AF against rotenone-induced cytotoxicity was confirmed by increased cell viability and longer dendritic lengths in PC12 and primary neuronal cells. Furthermore, in rotenone-treated PC12 cells, 1,5-AF upregulated peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) expression and enhanced its deacetylation, while increasing AMP-activated protein kinase (AMPK) phosphorylation. 1,5-AF treatment also increased mitochondrial activity in these cells. Moreover, PGC-1α silencing inhibited the cytoprotective and mitochondrial biogenic effects of 1,5-AF in PC12 cells. Therefore, 1,5-AF may activate PGC-1α through AMPK activation, thus leading to mitochondrial biogenic and cytoprotective effects. Together, our results suggest that 1,5-AF has therapeutic potential for development as a treatment for PD.

| S-EPMC8466044 | biostudies-literature

1,5-Anhydro-D-Fructose Exhibits Satiety Effects via the Activation of Oxytocin Neurons in the Paraventricular Nucleus.

Project description:1,5-Anhydro-D-fructose (1,5-AF) is a bioactive monosaccharide that is produced by the glycogenolysis in mammalians and is metabolized to 1,5-anhydro-D-glucitol (1,5-AG). 1,5-AG is used as a marker of glycemic control in diabetes patients. 1,5-AF has a variety of physiological activities, but its effects on energy metabolism, including feeding behavior, are unclarified. The present study examined whether 1,5-AF possesses the effect of satiety. Peroral administration of 1,5-AF, and not of 1,5-AG, suppressed daily food intake. Intracerebroventricular (ICV) administration of 1,5-AF also suppressed feeding. To investigate the neurons targeted by 1,5-AF, we investigated c-Fos expression in the hypothalamus and brain stem. ICV injection of 1,5-AF significantly increased c-Fos positive oxytocin neurons and mRNA expression of oxytocin in the paraventricular nucleus (PVN). Moreover, 1,5-AF increased cytosolic Ca2+ concentration of oxytocin neurons in the PVN. Furthermore, the satiety effect of 1,5-AF was abolished in oxytocin knockout mice. These findings reveal that 1,5-AF activates PVN oxytocin neurons to suppress feeding, indicating its potential as the energy storage monitoring messenger to the hypothalamus for integrative regulation of energy metabolism.

| S-EPMC10179633 | biostudies-literature

The structure of substrate-free 1,5-anhydro-D-fructose reductase from Sinorhizobium meliloti 1021 reveals an open enzyme conformation.

Project description:1,5-Anhydro-D-fructose (1,5-AF) is an interesting building block for enantioselective and stereoselective organic synthesis. Enzymes acting on this compound are potential targets for structure-based protein/enzyme design to extend the repertoire of catalytic modifications of this and related building blocks. Recombinant 1,5-anhydro-D-fructose reductase (AFR) from Sinorhizobium meliloti 1021 was produced in Escherichia coli, purified using a fused 6×His affinity tag and crystallized in complex with the cofactor NADP(H) using the hanging-drop technique. Its structure was determined to 1.93 Å resolution using molecular replacement. The structure displays an empty substrate-binding site and can be interpreted as an open conformation reflecting the enzyme state shortly after the release of product, presumably with bound oxidized cofactor NADP?. Docking simulations indicated that amino-acid residues Lys94, His151, Trp162, Arg163, Asp176 and His180 are involved in substrate binding, catalysis or product release. The side chain of Lys94 seems to have the ability to function as a molecular switch. The crystal structure helps to characterize the interface relevant for dimer formation as observed in solution. The crystal structure is compared with the structure of the homologue from S. morelense, which was solved in a closed conformation and for which dimer formation in solution could not be verified but seems to be likely based on the presented studies of S. meliloti AFR.

| S-EPMC3729156 | biostudies-literature

Role of the Gut Microbiome in Modulating Arthritis Progression in Mice.

Project description:Genetics alone cannot explain most cases of rheumatoid arthritis (RA). Thus, investigating environmental factors such as the gut microbiota may provide new insights into the initiation and progression of RA. In this study, we performed 16S rRNA sequencing to characterise the gut microbiota of DBA1 mice that did or did not develop arthritis after induction with collagen. We found that divergence in the distribution of microbiota after induction was pronounced and significant. Mice susceptible to collagen-induced arthritis (CIA) showed enriched operational taxonomic units (OTUs) affiliated with the genus Lactobacillus as the dominant genus prior to arthritis onset. With disease development, the abundance of OTUs affiliated with the families Bacteroidaceae, Lachnospiraceae, and S24-7 increased significantly in CIA-susceptible mice. Notably, germ-free mice conventionalized with the microbiota from CIA-susceptible mice showed a higher frequency of arthritis induction than those conventionalized with the microbiota from CIA-resistant mice. Consistently, the concentration of the cytokine interleukin-17 in serum and the proportions of CD8+T cells and Th17 lymphocytes in the spleen were significantly higher in the former group, whereas the abundances of dendritic cells, B cells, and Treg cells in the spleen were significantly lower. Our results suggest that the gut microbiome influences arthritis susceptibility.

| S-EPMC4969881 | biostudies-literature

Fiber supplementation protects from antibiotic-induced gut microbiome dysbiosis by modulating gut redox potential.

Project description:Antibiotic-induced gut dysbiosis (AID) is a frequent and serious side effect of antibiotic use and mitigating this dysbiosis is a critical therapeutic target. We propose that the host diet can modulate the chemical environment of the gut resulting in changes to the structure and function of the microbiome during antibiotic treatment. Gut dysbiosis is typically characterized by increases in aerobic respiratory bacterial metabolism, redox potential, and abundance of Proteobacteria. In this study, we explore dietary fiber supplements as potential modulators of the chemical environment in the gut to reduce this pattern of dysbiosis. Using defined-diets and whole-genome sequencing of female murine microbiomes during diet modulation and antibiotic treatment, we find that fiber prebiotics significantly reduced the impact of antibiotic treatment on microbiome composition and function. We observe reduced abundance of aerobic bacteria as well as metabolic pathways associated with oxidative metabolism. These metatranscriptomic results are corroborated by chemical measurements of eH and pH suggesting that fiber dampens the dysbiotic effects of antibiotics. This work indicates that fiber may act as a potential therapeutic for AID by modulating bacterial metabolism in the gut to prevent an increase in redox potential and protect commensal microbes during antibiotic treatment.

| S-EPMC10449846 | biostudies-literature

Liver Transcriptome and Gut Microbiome Analysis Reveals the Effects of High Fructose Corn Syrup in Mice.

Project description:High fructose corn syrup (HFCS) is a viscous mixture of glucose and fructose that is used primarily as a food additive. This article explored the effect of HFCS on lipid metabolism-expressed genes and the mouse gut microbiome. In total, ten 3-week-old male C57BL/6J mice were randomly divided into two groups, including the control group, given purified water (Group C) and 30% HFCS in water (Group H) for 16 weeks. Liver and colonic content were collected for transcriptome sequencing and 16S rRNA gene sequencing, respectively. HFCS significantly increased body weight, epididymal, perirenal fat weight in mice (p < 0.05), and the proportion of lipid droplets in liver tissue. The expression of the ELOVL fatty acid elongase 3 (Elovl3) gene was reduced, while Stearoyl-Coenzyme A desaturase 1 (Scd1), peroxisome proliferator activated receptor gamma (Pparg), fatty acid desaturase 2 (Fads2), acyl-CoA thioesterase 2 (Acot2), acyl-CoA thioesterase 2 (Acot3), acyl-CoA thioesterase 4 (Acot4), and fatty acid binding protein 2 (Fabp2) was increased in Group H. Compared with Group C, the abundance of Firmicutes was decreased in Group H, while the abundance of Bacteroidetes was increased, and the ratio of Firmicutes/Bacteroidetes was obviously decreased. At the genus level, the relative abundance of Bifidobacterium, Lactobacillus, Faecalibaculum, Erysipelatoclostridium, and Parasutterella was increased in Group H, whereas that of Staphylococcus, Peptococcus, Parabacteroides, Donghicola, and Turicibacter was reduced in Group H. Pparg, Acot2, Acot3, and Scd1 were positively correlated with Erysipelatoclostridium and negatively correlated with Parabacteroides, Staphylococcus, and Turicibacter. Bifidobacterium was negatively correlated with Elovl3. Overall, HFCS affects body lipid metabolism by affecting the expression of lipid metabolism genes in the liver through the gut microbiome.

| S-EPMC9280673 | biostudies-literature

Gut microbiome in modulating immune checkpoint inhibitors.

Project description:Gut microbiome has been increasingly recognized for its influence on a diverse array of human diseases including cancer, and may also influence the outcome of cancer therapies. A prime example is seen in immunotherapy, for which gut microbes determine the therapeutic responses associated with immune checkpoint inhibitors (ICIs) in preclinical models and patient cohorts. This evidence hints that inter-individual variations in the gut microbiota may account for the significant heterogeneity in immunotherapeutic responses to ICIs. Understanding the functional role of gut microbiome in regulating not only mucosal but also systemic immunity and cancer is critical to move forward in this era of precision medicine. What's more, microbiota can be modified via several different strategies that are essential for the efforts in expanding immunotherapy efficacy. This review summarizes latest knowledge about the interactions between microbiome, host immunity and cancer, and strategies to modulate the microbiome with implications to be translated into clinic. FUNDING: This study was supported by National Key R&D Program of China (No. 2020YFA0509200/2020YFA0509203), RGC Theme-based Res Scheme Hong Kong (T21-705/20-N).

| S-EPMC9297075 | biostudies-literature

COffee and Metabolites Modulating the Gut MicrobiomE in Colorectal caNCER

Project description:This is research study is assessing the effects of 6-g daily use of freeze-dried instant coffee on liver fat and fibrosis and the gut microbiome and metabolome in patients who have completed routine treatment (including surgery, chemotherapy and radiotherapy) for stage I-III colorectal cancer.

| 5568 | ecrin-mdr-crc

Development of Novel Low-Molecular-Mass Oil-gelling Agents: Synthesis and Physical Properties of 1,5-Anhydro-D-glucitol and 1,5-Anhydro-D-mannitol Protected with Saturated Linear Fatty Acids.

Project description:We have developed a novel low-molecular-mass oil-gelling agent that is electrically neutral, has no nitrogen atoms and consists only of cyclic sugar alcohols and saturated linear fatty acids. The cyclic sugar alcohols were 1,5-anhydro-D-glucitol (1,5-AG) and 1,5-anhydro-D-mannitol (1,5-AM) derived from starch via 1,5-anhydro-D-fructose. Various saturated linear fatty acids with 10 to 18 and 22 carbon atoms were introduced into all the hydroxy groups of 1,5-AG. Various saturated linear fatty acids with 13 to 18 and 22 carbon atoms were introduced into all the hydroxy groups of 1,5-AM. Initially, the gelling ability increased as the carbon number increased, but the gelling ability decreased as the carbon number increased beyond 17 carbons. This trend was similar for both 1,5-AG and 1,5-AM. A comparison of 1,5-AG and 1,5-AM derivatives revealed that 1,5-AG derivatives had greater gelling abilities for different kinds of oils at the same fatty acid length. Further, it was confirmed by SEM observations that a three-dimensional fibrous structure was formed, and this network structure formed the gel and held the oil. Here, we report the synthesis and characteristics of a novel low-molecular-weight gelling agent and its gelation mechanism.

| S-EPMC8373582 | biostudies-literature

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