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Gut Nov 2022In Europe, IBS is commonly treated with musculotropic spasmolytics (eg, otilonium bromide, OB). In tertiary care, a low fermentable oligosaccharides, disaccharides,... (Randomized Controlled Trial)
Randomized Controlled Trial
Diet or medication in primary care patients with IBS: the DOMINO study - a randomised trial supported by the Belgian Health Care Knowledge Centre (KCE Trials Programme) and the Rome Foundation Research Institute.
BACKGROUND
In Europe, IBS is commonly treated with musculotropic spasmolytics (eg, otilonium bromide, OB). In tertiary care, a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet provides significant improvement. Yet, dietary treatment remains to be explored in primary care. We evaluated the effect of a smartphone FODMAP-lowering diet application versus OB on symptoms in primary care IBS.
METHODS
IBS patients, recruited by primary care physicians, were randomised to 8 weeks of OB (40 mg three times a day) or diet and followed for 24 weeks. We compared IBS Symptom Severity Score and the proportion of responders (improvement ≥50 points) in all patients and the subgroup fulfilling Rome IV criteria (Rome+). We also evaluated treatment efficacy, quality of life, anxiety, depression, somatic symptom severity (Patient Health Questionnaire (PHQ15, PHQ9)) and treatment adherence and analysed predictors of response.
RESULTS
459 primary care IBS patients (41±15 years, 76% female, 70% Rome+) were randomised. The responder rate after 8 weeks was significantly higher with diet compared with OB (71% (155/218) vs 61% (133/217), p=0.03) and more pronounced in Rome+ (77% (118/153) vs 62% (98/158), p=0.004). Patients allocated to diet (199/212) were 94% adherent compared with 73% with OB (148/202) (p<0.001). The significantly higher response rate with diet was already observed after 4 weeks (62% (132/213) vs 51% (110/215), p=0.02) and a high symptom response persisted during follow-up. Predictors of response were female gender (OR=2.08, p=0.04) for diet and PHQ15 (OR=1.10, p=0.02) for OB.
CONCLUSION
In primary care IBS patients, a FODMAP-lowering diet application was superior to a spasmolytic agent in improving IBS symptoms. A FODMAP-lowering diet should be considered the first-line treatment for IBS in primary care.
TRIAL REGISTRATION NUMBER
NCT04270487.
Topics: Academies and Institutes; Belgium; Delivery of Health Care; Diet; Disaccharides; Female; Fermentation; Humans; Irritable Bowel Syndrome; Male; Monosaccharides; Oligosaccharides; Parasympatholytics; Primary Health Care; Quality of Life; Rome
PubMed: 35483886
DOI: 10.1136/gutjnl-2021-325821 -
Biomolecules May 2020Trehalose is a natural disaccharide synthesized in various life forms, but not found in vertebrates. An increasing body of evidence demonstrates exceptional... (Review)
Review
Trehalose is a natural disaccharide synthesized in various life forms, but not found in vertebrates. An increasing body of evidence demonstrates exceptional bioprotective characteristics of trehalose. This review discusses the scientific findings on potential functions of trehalose in oxidative stress, protein clearance, and inflammation, with an emphasis on animal models and clinical trials in ophthalmology. The main objective is to help understand the beneficial effects of trehalose in clinical trials and practice, especially in patients suffering from ocular surface disease. The discussion is supplemented with an overview of patents for the use of trehalose in dry eye and with prospects for the 2020s.
Topics: Animals; Antioxidants; Clinical Trials as Topic; Cornea; Corneal Diseases; Dry Eye Syndromes; Humans; Trehalose
PubMed: 32466265
DOI: 10.3390/biom10050809 -
Carbohydrate Research Nov 2023Thio sugars are carbohydrate derivatives in which one or more oxygen atoms have been replaced with sulfur. Thio sugars are effective inhibitors of glycosylases, have... (Review)
Review
Thio sugars are carbohydrate derivatives in which one or more oxygen atoms have been replaced with sulfur. Thio sugars are effective inhibitors of glycosylases, have considerable therapeutic potential, and are used as drugs in the treatment of diabetes and infectious diseases. The development of this branch of carbohydrate chemistry would not be possible without the development of novel methods for its synthesis and the analysis of their biochemical properties. In this Review Article, we summarize our findings on the biological properties of a collection of thio sugars and their derivatives synthesized by the Witczak and Bielski team using their original methods based on the Michael addition of sugar thiols to levoglucosenone.
Topics: Disaccharides; Thiosugars
PubMed: 37708795
DOI: 10.1016/j.carres.2023.108934 -
Nutrients Mar 2023Trehalose is a naturally occurring, non-reducing disaccharide comprising two covalently-linked glucose molecules. It possesses unique physiochemical properties, which... (Review)
Review
Trehalose is a naturally occurring, non-reducing disaccharide comprising two covalently-linked glucose molecules. It possesses unique physiochemical properties, which account for multiple biological roles in a variety of prokaryotic and eukaryotic organisms. In the past few decades, intensive research on trehalose has uncovered its functions, and extended its uses as a sweetener and stabilizer in the food, medical, pharmaceutical, and cosmetic industries. Further, increased dietary trehalose consumption has sparked research on how trehalose affects the gut microbiome. In addition to its role as a dietary sugar, trehalose has gained attention for its ability to modulate glucose homeostasis, and potentially as a therapeutic agent for diabetes. This review discusses the bioactive effects of dietary trehalose, highlighting its promise in future industrial and scientific contributions.
Topics: Humans; Trehalose; Diabetes Mellitus; Excipients; Nutrients; Glucose
PubMed: 36986123
DOI: 10.3390/nu15061393 -
Analytical Chemistry Oct 2020The inherent structural complexity and diversity of glycans pose a major analytical challenge to their structural analysis. Radical chemistry has gained considerable...
The inherent structural complexity and diversity of glycans pose a major analytical challenge to their structural analysis. Radical chemistry has gained considerable momentum in the field of mass spectrometric biomolecule analysis, including proteomics, glycomics, and lipidomics. Herein, seven isomeric disaccharides and two isomeric tetrasaccharides with subtle structural differences are distinguished rapidly and accurately via one-step radical-induced dissociation. The free-radical-activated glycan-sequencing reagent (FRAGS) selectively conjugates to the unique reducing terminus of glycans in which a localized nascent free radical is generated upon collisional activation and simultaneously induces glycan fragmentation. Higher-energy collisional dissociation (HCD) and collision-induced dissociation (CID) are employed to provide complementary structural information for the identification and discrimination of glycan isomers by providing different fragmentation pathways to generate informative, structurally significant product ions. Furthermore, multiple-stage tandem mass spectrometry (MS CID) provides supplementary and valuable structural information through the generation of characteristic parent-structure-dependent fragment ions.
Topics: Chromatography, High Pressure Liquid; Disaccharides; Free Radicals; Isomerism; Polysaccharides; Tandem Mass Spectrometry
PubMed: 32935980
DOI: 10.1021/acs.analchem.0c02213 -
Molecules (Basel, Switzerland) Nov 2019lectin (CNL) is present in fruiting bodies of clouded agaric along with several similar isolectins that are all small and stable proteins. It is a beta-trefoil type... (Review)
Review
lectin (CNL) is present in fruiting bodies of clouded agaric along with several similar isolectins that are all small and stable proteins. It is a beta-trefoil type lectin forming homodimers that are essential for its functionality. It binds specifically ,'-diacetyllactosediamine (GalNAcβ1-4GlcNAc, LacDiNac) and human blood group A determinant-containing glycan epitopes. Its most probable function is to defend fruiting bodies against predators and parasites. In addition, an endogenous regulatory function is possible for CNL, as indicated by its interaction with fungal protease inhibitors sharing the beta-trefoil fold. CNL is toxic to insects, nematodes and amoebae, as well as to leukemic T-cell lines. Bivalent carbohydrate binding is essential for the toxicity of CNL, against both invertebrates and cancer-derived cell lines. In addition, CNL exhibits potent immunostimulation of human dendritic cells, resulting in a strong T helper cell type 1 response. Based on its unique characteristics, CNL is a promising candidate for applications in human and veterinary medicine as well as in agriculture, for plant protection.
Topics: Agaricales; Animals; Fungal Proteins; Lactose; Lectins
PubMed: 31756927
DOI: 10.3390/molecules24234204 -
Clinical Nutrition (Edinburgh, Scotland) Nov 2022Ketogenic medium-chain fatty acids (MCFAs) with profound health benefits are commonly found in dairy products, palm kernel oil and coconut oil. We hypothesize that... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
Ketogenic medium-chain fatty acids (MCFAs) with profound health benefits are commonly found in dairy products, palm kernel oil and coconut oil. We hypothesize that magnesium (Mg) supplementation leads to enhanced gut microbial production of MCFAs and, in turn, increased circulating MCFAs levels.
METHODS
We tested this hypothesis in the Personalized Prevention of Colorectal Cancer Trial (PPCCT) (NCT01105169), a double-blind 2 × 2 factorial randomized controlled trial enrolling 240 participants. Six 24-h dietary recalls were performed for all participants at the baseline and during the intervention period. Based on the baseline 24-h dietary recalls, the Mg treatment used a personalized dose of Mg supplementation that would reduce the calcium (Ca): Mg intake ratio to around 2.3. We measured plasma MCFAs, sugars, ketone bodies and tricarboxylic acid cycle (TCA cycle) metabolites using the Metabolon's global Precision Metabolomics™ LC-MS platform. Whole-genome shotgun metagenomics (WGS) sequencing was performed to assess microbiota in stool samples, rectal swabs, and rectal biopsies.
RESULTS
Personalized Mg treatment (mean dose 205.58 mg/day with a range from 77.25 to 389.55 mg/day) significantly increased the plasma levels of C7:0, C8:0, and combined C7:0 and C8:0 by 18.45%, 25.28%, and 24.20%, respectively, compared to 14.15%, 10.12%, and 12.62% decreases in the placebo arm. The effects remain significant after adjusting for age, sex, race and baseline level (P = 0.0126, P = 0.0162, and P = 0.0031, respectively) and FDR correction at 0.05 (q = 0.0324 for both C7:0 and C8:0). Mg treatment significantly reduced the plasma level of sucrose compared to the placebo arm (P = 0.0036 for multivariable-adjusted and P = 0.0216 for additional FDR correction model) whereas alterations in daily intakes of sucrose, fructose, glucose, maltose and C8:0 from baseline to the end of trial did not differ between two arms. Mediation analysis showed that combined C7:0 and C8:0 partially mediated the effects of Mg treatment on total and individual ketone bodies (P for indirect effect = 0.0045, 0.0043, and 0.03, respectively). The changes in plasma levels of C7:0 and C8:0 were significantly and positively correlated with the alterations in stool microbiome α diversity (r = 0.51, p = 0.0023 and r = 0.34, p = 0.0497, respectively) as well as in stool abundance for the signatures of MCFAs-related microbiota with acyl-ACP thioesterase gene producing C7:0 (r = 0.46, p = 0.0067) and C8:0 (r = 0.49, p = 0.003), respectively, following Mg treatment.
CONCLUSIONS
Optimizing Ca:Mg intake ratios to around 2.3 through 12-week personalized Mg supplementation leads to increased circulating levels of MCFAs (i.e. C7:0 and C8:0), which is attributed to enhanced production from gut microbial fermentation and, maybe, sucrose consumption.
Topics: Humans; Gastrointestinal Microbiome; Coconut Oil; Calcium; Maltose; Magnesium; Fatty Acids; Ketone Bodies; Sucrose; Fructose; Glucose
PubMed: 36223712
DOI: 10.1016/j.clnu.2022.08.031 -
Sensors (Basel, Switzerland) Dec 2022Sucrose is a primary metabolite in plants, a source of energy, a source of carbon atoms for growth and development, and a regulator of biochemical processes. Most of the... (Review)
Review
Sucrose is a primary metabolite in plants, a source of energy, a source of carbon atoms for growth and development, and a regulator of biochemical processes. Most of the traditional analytical chemistry methods for sucrose quantification in plants require sample treatment (with consequent tissue destruction) and complex facilities, that do not allow real-time sucrose quantification at ultra-low concentrations (nM to pM range) under in vivo conditions, limiting our understanding of sucrose roles in plant physiology across different plant tissues and cellular compartments. Some of the above-mentioned problems may be circumvented with the use of bio-compatible ligands for molecular recognition of sucrose. Nevertheless, problems such as the signal-noise ratio, stability, and selectivity are some of the main challenges limiting the use of molecular recognition methods for the in vivo quantification of sucrose. In this review, we provide a critical analysis of the existing analytical chemistry tools, biosensors, and synthetic ligands, for sucrose quantification and discuss the most promising paths to improve upon its limits of detection. Our goal is to highlight the criteria design need for real-time, in vivo, highly sensitive and selective sucrose sensing capabilities to enable further our understanding of living organisms, the development of new plant breeding strategies for increased crop productivity and sustainability, and ultimately to contribute to the overarching need for food security.
Topics: Sucrose; Carbon; Chemistry, Analytic; Crop Production; Recognition, Psychology
PubMed: 36502213
DOI: 10.3390/s22239511 -
Neurotherapeutics : the Journal of the... Mar 2023Spinal and bulbar muscular atrophy (SBMA) is characterized by motor neuron (MN) degeneration that leads to slowly progressive muscle weakness. It is considered a...
Spinal and bulbar muscular atrophy (SBMA) is characterized by motor neuron (MN) degeneration that leads to slowly progressive muscle weakness. It is considered a neuromuscular disease since muscle has a primary role in disease onset and progression. SBMA is caused by a CAG triplet repeat expansion in the androgen receptor (AR) gene. The translated poly-glutamine (polyQ) tract confers a toxic gain of function to the mutant AR altering its folding, causing its aggregation into intracellular inclusions, and impairing the autophagic flux. In an in vitro SBMA neuronal model, we previously showed that the antiandrogen bicalutamide and trehalose, a natural disaccharide stimulating autophagy, block ARpolyQ activation, reduce its nuclear translocation and toxicity and facilitate the autophagic degradation of cytoplasmic AR aggregates. Here, in a knock-in SBMA mouse model (KI AR113Q), we show that bicalutamide and trehalose ameliorated SBMA pathology. Bicalutamide reversed the formation of the AR insoluble forms in KI AR113Q muscle, preventing autophagic flux blockage. We demonstrated that apoptosis is activated in KI AR113Q muscle, and that both compounds prevented its activation. We detected a decrease of mtDNA and an increase of OXPHOS enzymes, already at early symptomatic stages; these alterations were reverted by trehalose. Overall, bicalutamide and/or trehalose led to a partial recovery of muscle morphology and function, and improved SBMA mouse motor behavior, inducing an extension of their survival. Thus, bicalutamide and trehalose, by counteracting ARpolyQ toxicity in skeletal muscle, are valuable candidates for future clinical trials in SBMA patients.
Topics: Mice; Animals; Bulbo-Spinal Atrophy, X-Linked; Trehalose; Receptors, Androgen; Muscular Atrophy, Spinal; Anilides; Mice, Transgenic
PubMed: 36717478
DOI: 10.1007/s13311-023-01343-x -
Gastroenterology Aug 2021Oral monosaccharides and disaccharides are used to measure in vivo human gut permeability through urinary excretion. (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Oral monosaccharides and disaccharides are used to measure in vivo human gut permeability through urinary excretion.
AIMS
The aims were as follows: (1) to obtain normative data on small intestinal and colonic permeability; (2) to assess variance on standard 16 g fiber diet performed twice; (3) to determine whether dietary fiber influences gut permeability measurements; and (4) to present pilot data using 2 selected probes in patients with diarrhea-predominant irritable bowel syndrome (IBS-D).
METHODS
Sixty healthy female and male adults, age 18-70 years, participated in 3 randomized studies (2 studies on 16.25 g and 1 study on 32.5 g fiber) in otherwise standardized diets. At each test, the following sugars were ingested: C-mannitol, C-mannitol, rhamnose (monosaccharides), sucralose, and lactulose (disaccharides). Standardized meals were administered from 24 hours before and during 24 hours post-sugars with 3 urine collections: 0-2, 2-8, and 8-24 hours. Sugars were measured using high-performance liquid chromatography-tandem mass spectrometry. Eighteen patients with IBS-D underwent 24-hour excretion studies after oral C-mannitol and lactulose.
RESULTS
Baseline sugars (>3-fold above lower limits of quantitation) were identified in the 3 studies: C-mannitol in all participants; sucralose in 4-8, and rhamnose in 1-3. Median excretions/24 h (percentage of administered dose) for C-mannitol, rhamnose, lactulose, and sucralose were ∼30%, ∼15%, 0.32%, and 2.3%, respectively. C-mannitol and rhamnose reflected mainly small intestinal permeability. Intraindividual saccharide excretions were consistent, with minor differences with 16.25 g vs 32.5 g fiber diets. Median interindividual coefficient of variation was 76.5% (10-90 percentile: 34.6-111.0). There were no significant effects of sex, age, or body mass index on permeability measurements in health. C-mannitol measurements are feasible in IBS-D.
CONCLUSIONS
Baseline C-mannitol excretion precludes its use; C-mannitol is the preferred probe for small intestinal permeability.
Topics: Administration, Oral; Adult; Aged; Biomarkers; Chromatography, High Pressure Liquid; Colon; Cross-Over Studies; Diagnostic Techniques, Digestive System; Diarrhea; Dietary Fiber; Disaccharides; Female; Healthy Volunteers; Humans; Intestinal Mucosa; Intestine, Small; Irritable Bowel Syndrome; Male; Middle Aged; Monosaccharides; Permeability; Pilot Projects; Predictive Value of Tests; Renal Elimination; Reproducibility of Results; Tandem Mass Spectrometry; Urinalysis
PubMed: 33865841
DOI: 10.1053/j.gastro.2021.04.020