Explore the vast range of titles available.

Yeast mannan (YM) is an indigestible water-soluble polysaccharide of the yeast cell wall. In vitro fecal fermentation studies showed that YM could exhibit a notable prebiotic effect. The aim of this randomized, double-blind, placebo-controlled study was to assess the efficacy of YM intake on the intestinal environment and skin condition. One hundred and ten healthy female subjects aged 30–49 years were supplemented with YM or placebo for eight weeks. Skin dryness was set as the primary endpoint. No side effects were observed during the study. Microbiota analyses revealed that YM intake selectively increased the relative abundance of Bacteroides thetaiotaomicron and Bacteroides ovatus compared to that by placebo. Feces and urine analyses showed that YM intake lowered the concentration of fecal p-cresol, indole, and skatole, and elevated urinal equol levels compared to those in placebo. Furthermore, YM supplementation ameliorated subjective skin dryness. This study suggests that YM intake could promote beneficial Bacteroides and improve the intestinal environment and skin condition.

Microbial exopolysaccharides from extreme environments are increasingly becoming valuable candidates for drug development. In this study, four fractions named XL-1, XMRS-1, XL-1-D, and XMRS-1-D were isolated and purified from the hadal bacterium Psychrobacter pulmonis by column chromatography. The structural features of these fractions were characterized by molecular weight, monosaccharide composition, Fourier transform infrared (FTIR) spectrum, amino acid analysis and NMR. The results showed that XL-1 and XMRS-1 were mainly composed of mannose, glucose, and glucosamine, while XL-1-D and XMRS-1-D were mainly composed of mannose. In vitro bioactivity assays demonstrated that all four fractions significantly enhanced RAW264.7 macrophage proliferation and phagocytosis, stimulated nitric oxide (NO) and reactive oxygen species (ROS) production, and induced the secretion of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and the expression of inducible nitric oxide synthase (iNOS) mRNA. Moreover, plate cloning tests, cell scratch tests, and apoptosis assays, along with RT-qPCR analysis, demonstrated that the four fractions significantly inhibited A549 cells’ proliferation. Specifically, XMRS-1 and XMRS-1-D upregulated Bax, Caspase-3, Caspase-8, and Caspase-9, while downregulating Bcl-2, suggesting transcriptional activation of apoptosis-related pathways. These results offered a reference for the further development and utilization of this hadal bacterium in the future.

(1) Background: Alterations in the structural composition of the human gut microbiota have been identified in various disease entities along with exciting mechanistic clues by reductionist gnotobiotic modeling. Improving health by beneficially modulating an altered microbiota is a promising treatment approach. Prebiotics, substrates selectively used by host microorganisms conferring a health benefit, are broadly used for dietary and clinical interventions. Herein, we sought to investigate the microbiota-modelling effects of the soluble fiber, partially hydrolyzed guar gum (PHGG). (2) Methods: We performed a 9 week clinical trial in 20 healthy volunteers that included three weeks of a lead-in period, followed by three weeks of an intervention phase, wherein study subjects received 5 g PHGG up to three times per day, and concluding with a three-week washout period. A stool diary was kept on a daily basis, and clinical data along with serum/plasma and stool samples were collected on a weekly basis. PHGG-induced alterations of the gut microbiota were studied by 16S metagenomics of the V1–V3 and V3–V4 regions. To gain functional insight, we further studied stool metabolites using nuclear magnetic resonance (NMR) spectroscopy. (3) Results: In healthy subjects, PHGG had significant effects on stool frequency and consistency. These effects were paralleled by changes in α- (species evenness) and β-diversity (Bray–Curtis distances), along with increasing abundances of metabolites including butyrate, acetate and various amino acids. On a taxonomic level, PHGG intake was associated with a bloom in Ruminococcus, Fusicatenibacter, Faecalibacterium and Bacteroides and a reduction in Roseburia, Lachnospiracea and Blautia. The majority of effects disappeared after stopping the prebiotic and most effects tended to be more pronounced in male participants. (4) Conclusions: Herein, we describe novel aspects of the prebiotic PHGG on compositional and functional properties of the healthy human microbiota.

Partially hydrolyzed guar gum (PHGG) is a water-soluble dietary fiber and is used in solid and liquid food to regulate gut function. The aim of this study was to investigate effects of PHGG on bowel movements (stool form and frequency), plasma bile acids, quality of life, and gut microbiota of healthy volunteers with a tendency toward diarrhea, i.e., irritable bowel syndrome diarrhea (IBS-D)-like symptoms. A randomized, double-blind, placebo-controlled, and parallel trial was performed on 44 healthy volunteers (22 males, 22 females, 41.9 ± 6.3 years old (average ± SD)) with minimum 7 bowel movements every week, wherein above 50% of their stool was between the Bristol stool scale (BSS) value of 5 and 6. Intake of the PHGG for 3 months significantly improved stool form, evaluated using BSS, and had no effects on stool frequency. BSS was significantly normalized in the group consuming the PHGG compared with the placebo. Comprehensive fecal microbiome analysis by the 16S rRNA-sequence method detected significant changes in the ratio of some bacteria, such as an increase of Bifidobacterium (p < 0.05) in the PHGG group. Our results suggest that intake of PHGG improves human stool form via regulating intestinal microbiota.

Hemicellulose is a complex group of heterogeneous polymers and represents one of the major sources of renewable organic matter. Mannan is one of the major constituent groups of hemicellulose in the wall of higher plants. It comprises linear or branched polymers derived from sugars such as d-mannose, d-galactose, and d-glucose. The principal component of softwood hemicellulose is glucomannan. Structural studies revealed that the galactosyl side chain hydrogen interacts to the mannan backbone intramolecularly and provides structural stability. Differences in the distribution of d-galactosyl units along the mannan structure are found in galactomannans from different sources. Acetyl groups were identified and distributed irregularly in glucomannan. Some of the mannosyl units of galactoglucomannan are partially substituted by O-acetyl groups. Some unusual structures are found in the mannan family from seaweed, showing a complex system of sulfated structure. Endohydrolases and exohydrolases are involved in the breakdown of the mannan backbone to oligosaccharides or fermentable sugars. The main-chain mannan-degrading enzymes include β-mannanase, β-glucosidase, and β-mannosidase. Additional enzymes such as acetyl mannan esterase and α-galactosidase are required to remove side-chain substituents that are attached at various points on mannan, creating more sites for subsequent enzymatic hydrolysis. Mannan-degrading enzymes have found applications in the pharmaceutical, food, feed, and pulp and paper industries. This review reports the structure of mannans and some biochemical properties and applications of mannan-degrading enzymes.

Targeting antigens to dendritic cell receptors has recently become a popular approach to inducing effective immune responses against cancer antigens. Almost 20 years ago, however, we demonstrated that targeting the mannose receptor on macrophages and dendritic cells leads to strong cellular immune responses. We conducted numerous human clinical trials demonstrating the effectiveness of oxidized mannan-MUC1 (M-FP) in MUC1 adenocarcinoma patients. In one trial, the 5-8-year follow-up of breast cancer patients vaccinated with M-FP was published previously; we now report here the 12-15-year follow-up. Details regarding the preparation of the vaccine, inclusion and exclusion criteria, immunotherapy and follow-up schedule, were published previously. The follow-up at 12-15 years showed that the recurrence rate in patients receiving placebo was 60% (nine of 15). In those receiving immunotherapy (M-FP), the rate was 12.5% (two of 16). The time of recurrence in the placebo group ranged from 7 to 180 months (mean: 65.8 months) and in the two patients of the vaccine group, the recurrence appeared at 95 and 141 months (mean: 118 months) after surgery. These findings are statistically significant (p = 0.02 for survival and p = 0.009 for percentage of patients cancer-free). All patients injected with M-FP showed no evidence of toxic effects or signs of autoimmunity during the 12-15-year follow-up. The preliminary evidence indicates that M-FP is beneficial in the overall survival of early-stage breast cancer patients. This long-term clinical follow-up of patients strongly supports the necessity for a large Phase III study of direct M-FP injection in early-stage breast cancer patients, to evaluate immunotherapy as an adjuvant treatment for breast cancer.

Yeasts, which have been a component of the human diet for at least 7,000 years, possess an elaborate cell wall α-mannan. The influence of yeast mannan on the ecology of the human microbiota is unknown. Here we show that yeast α-mannan is a viable food source for the Gram-negative bacterium Bacteroides thetaiotaomicron , a dominant member of the microbiota. Detailed biochemical analysis and targeted gene disruption studies support a model whereby limited cleavage of α-mannan on the surface generates large oligosaccharides that are subsequently depolymerized to mannose by the action of periplasmic enzymes. Co-culturing studies showed that metabolism of yeast mannan by B. thetaiotaomicron presents a ‘selfish’ model for the catabolism of this difficult to breakdown polysaccharide. Genomic comparison with B. thetaiotaomicron in conjunction with cell culture studies show that a cohort of highly successful members of the microbiota has evolved to consume sterically-restricted yeast glycans, an adaptation that may reflect the incorporation of eukaryotic microorganisms into the human diet. Mannan, a component of yeast cell walls, is shown to be a viable food source for Bacteroides thetaiotamicron , a dominant member of the gut microbiota, which catabolizes the mannan ‘selfishly’—countering the general assumption that multiple members of the gut microbiota take a role in, and benefit from, polysaccharide catabolism. A gut microbe with a taste for yeast Harry Gilbert and colleagues show that Bacteroides thetaiotaomicron , a dominant member of the human gut microbiota, can utilize α-mannose-containing complex carbohydrates derived from both host glycoproteins and yeast-derived dietary polysaccharides as a viable food source. The authors identify the genetic loci that encode the machinery that allows B. thetaiotamicron to metabolize α-mannan via large oligosaccharides that are subsequently depolymerized to mannose by the action of periplasmic enzymes. Co-culturing studies reveal a 'selfish' model for α-mannan catabolism, which runs counter to the general assumption that multiple members of the gut microbiota take a role in, and benefit from, polysaccharide catabolism. This study provides insight into how the evolution of glycan degradation in the human gut microbiota mirrors dietary changes during the course of human evolution, as yeast α-mannan has become a ubiquitous dietary component of our diet only since the acquisition of the modern human diet.

Switching macrophages from a pro-tumor type to an anti-tumor state is a promising strategy for cancer immunotherapy. Existing agents, many derived from bacterial components, have safety or specificity concerns. Here, we postulate that the structures of the bacterial signals can be mimicked by using non-toxic biomolecules of simple design. Based on bioactivity screening, we devise a glucomannan polysaccharide with acetyl modification at a degree of 1.8 (acGM-1.8), which specifically activates toll-like receptor 2 (TLR2) signaling and consequently induces macrophages into an anti-tumor phenotype. For acGM-1.8, the degree of acetyl modification, glucomannan pattern, and acetylation-induced assembly are three crucial factors for its bioactivity. In mice, intratumoral injection of acGM-1.8 suppresses the growth of two tumor models, and this polysaccharide demonstrates higher safety than four classical TLR agonists. In summary, we report the design of a new, safe, and specific TLR2 agonist that can generate macrophages with strong anti-tumor potential in mice. Turning tumour promoting macrophages into an anti-tumour phenotype is an attractive therapeutic strategy. Here, the authors develop a polysaccharide-based structure that mimicks pathogen-associated molecular patterns and, by activating the toll-like receptors on macrophage surface, promotes a safe anti-tumour immune response in mouse models.

A diet rich in fibre seems to protect against the metabolic syndrome (MetS), but there is scarce information about the role of fibre intake in patients with the MetS and diabetes. The aim of the present study was to evaluate the effects of soluble fibre from partially hydrolysed guar gum (PHGG) on the MetS and cardiovascular risk factors in patients with type 2 diabetes. In the present randomised controlled clinical trial, forty-four patients with type 2 diabetes (males 38·6 %, age 62 (sd 9) years, diabetes duration 14·2 (sd 9·6) years) and the MetS underwent clinical, laboratory and dietary evaluations at baseline, 4 and 6 weeks. All patients followed their usual diet and the intervention group (n 23) received an additional 10 g/d of PHGG. In the intervention group, waist circumference (WC), glycated Hb (HbA1c), 24 h urinary albumin excretion (UAE) and serum trans-fatty acids (FA) were reduced in comparison with baseline after 4 and 6 weeks: WC 103·5 (sd 9·5) to 102·1 (sd 10) to 102·3 (sd 9·7) cm; HbA1c 6·88 (sd 0·99) to 6·64 (sd 0·94) to 6·57 (sd 0·84) %; 24 h UAE 6·8 (interquartile range 3·0–17·5) to 4·5 (interquartile range 3·0–10·5) to 6·2 (interquartile range 3·0–9·5) mg; trans-FA 71 (interquartile range 46–137) to 67 (interquartile range 48–98) to 57 (interquartile range 30–110) mg/l (P< 0·05 for all). The only change in the control group was weight reduction: 77·0 (sd 13·5) to 76·2 (sd 13·3) to 76·1 (sd 13·4) kg (P= 0·005). Other MetS components (blood pressure, TAG, HDL-cholesterol, fasting plasma glucose), total and LDL-cholesterol, C-reactive protein and endothelin-1 did not change in either group. In patients with type 2 diabetes and the MetS, the addition of PHGG to the usual diet improved cardiovascular and metabolic profiles by reducing WC, HbA1c, UAE and trans-FA.