543 results found
Lees HJ, Swann JR, Poucher S, et al., 2019, Obesity and Cage Environment Modulate Metabolism in the Zucker Rat: A Multiple Biological Matrix Approach to Characterizing Metabolic Phenomena., J Proteome Res, Vol: 18, Pages: 2160-2174
Obesity and its comorbidities are increasing worldwide imposing a heavy socioeconomic burden. The effects of obesity on the metabolic profiles of tissues (liver, kidney, pancreas), urine, and the systemic circulation were investigated in the Zucker rat model using 1H NMR spectroscopy coupled to multivariate statistical analysis. The metabolic profiles of the obese ( fa/ fa) animals were clearly differentiated from the two phenotypically lean phenotypes, ((+/+) and ( fa/+)) within each biological compartment studied, and across all matrices combined. No significant differences were observed between the metabolic profiles of the genotypically distinct lean strains. Obese Zucker rats were characterized by higher relative concentrations of blood lipid species, cross-compartmental amino acids (particularly BCAAs), urinary and liver metabolites relating to the TCA cycle and glucose metabolism; and lower amounts of urinary gut microbial-host cometabolites, and intermatrix metabolites associated with creatine metabolism. Further to this, the obese Zucker rat metabotype was defined by significant metabolic alterations relating to disruptions in the metabolism of choline across all compartments analyzed. The cage environment was found to have a significant effect on urinary metabolites related to gut-microbial metabolism, with additional cage-microenvironment trends also observed in liver, kidney, and pancreas. This study emphasizes the value in metabotyping multiple biological matrices simultaneously to gain a better understanding of systemic perturbations in metabolism, and also underscores the need for control or evaluation of cage environment when designing and interpreting data from metabonomic studies in animal models.
Gooderham N, Alkandari A, Ashrafian H, et al., Bariatric surgery modulates urinary levels of microRNAs involved in the regulation of renal function, Frontiers in Endocrinology, ISSN: 1664-2392
Hegade VS, Pechlivanis A, McDonald JAK, et al., 2019, Autotaxin, bile acid profile and effect of ileal bile acid transporter inhibition in primary biliary cholangitis patients with pruritus, LIVER INTERNATIONAL, Vol: 39, Pages: 967-975, ISSN: 1478-3223
Whiley L, Nye LC, Grant I, et al., 2019, Ultrahigh-Performance Liquid Chromatography Tandem Mass Spectrometry with Electrospray Ionization Quantification of Tryptophan Metabolites and Markers of Gut Health in Serum and Plasma-Application to Clinical and Epidemiology Cohorts, ANALYTICAL CHEMISTRY, Vol: 91, Pages: 5207-5216, ISSN: 0003-2700
Byrne CS, Chambers ES, Preston T, et al., 2019, Effects of Inulin Propionate Ester Incorporated into Palatable Food Products on Appetite and Resting Energy Expenditure: A Randomised Crossover Study., Nutrients, Vol: 11
Supplementation with inulin-propionate ester (IPE), which delivers propionate to the colon, suppresses ad libitum energy intake and stimulates the release of satiety hormones acutely in humans, and prevents weight gain. In order to determine whether IPE remains effective when incorporated into food products (FP), IPE needs to be added to a widely accepted food system. A bread roll and fruit smoothie were produced. Twenty-one healthy overweight and obese humans participated. Participants attended an acclimatisation visit and a control visit where they consumed un-supplemented food products (FP). Participants then consumed supplemented-FP, containing 10 g/d inulin or IPE for six days followed by a post-supplementation visit in a randomised crossover design. On study visits, supplemented-FP were consumed for the seventh time and ad libitum energy intake was assessed 420 min later. Blood samples were collected to assess hormones and metabolites. Resting energy expenditure (REE) was measured using indirect calorimetry. Taste and appearance ratings were similar between FP. Ad libitum energy intake was significantly different between treatments, due to a decreased intake following IPE-FP. These observations were not related to changes in blood hormones and metabolites. There was an increase in REE following IPE-FP. However, this effect was lost after correcting for changes in fat free mass. Our results suggest that IPE suppresses appetite and may alter REE following its incorporation into palatable food products.
Ovadia C, Perdones-Montero A, Spagou K, et al., 2019, Enhanced microbial bile acid deconjugation and impaired ileal uptake in pregnancy repress intestinal regulation of bile acid synthesis., Hepatology
Pregnancy is associated with progressive hypercholanemia, hypercholesterolemia and hypertriglyceridemia, which can result in metabolic disease in susceptible women. Gut signals modify hepatic homeostatic pathways, linking intestinal content to metabolic activity. We sought to identify whether enteric endocrine signals contribute to raised serum bile acids observed in human and murine pregnancies, by measuring fibroblast growth factor (FGF)19/15 protein and mRNA levels, and 7α-hydroxy-4-cholesten-3-one. Terminal ileal farnesoid X receptor(FXR)-mediated gene expression and apical sodium bile acid transporter (ASBT) protein concentration were measured by qPCR and western blotting. Shotgun whole genome sequencing and UPLC-MS were used to determine the cecal microbiome and metabonome. Targeted and untargeted pathway analyses were performed to predict the systemic effects of the altered metagenome and metabolite profiles. Dietary cholic acid supplementation was used to determine whether the observed alterations could be overcome by intestinal bile acids functioning as FXR agonists. Human and murine pregnancy were associated with reduced intestinal FXR signaling, with lower FGF19/15 and resultant increased hepatic bile acid synthesis. Terminal ileal ASBT protein was reduced in murine pregnancy. Cecal bile acid conjugation was reduced in pregnancy due to elevated bile salt hydrolase-producing Bacteroidetes. Cholic acid supplementation induced intestinal FXR signaling, which was not abrogated by pregnancy, with strikingly similar changes to the microbiota and metabonome as identified in pregnancy. CONCLUSION: the altered intestinal microbiota of pregnancy enhance bile acid deconjugation, reducing ileal bile acid uptake and lowering FXR induction in enterocytes. This exacerbates the effects mediated by reduced bile acid uptake transporters in pregnancy. Thus, in pregnant women and mice, there is reduced FGF19/15-mediated hepatic repression of hepatic bile acid synthesis
Chambers ES, Byrne CS, Morrison DJ, et al., 2019, Dietary supplementation with inulin-propionate ester or inulin improves insulin sensitivity in adults with overweight and obesity with distinct effects on the gut microbiota, plasma metabolome and systemic inflammatory responses: a randomised cross-over trial., Gut
OBJECTIVE: To investigate the underlying mechanisms behind changes in glucose homeostasis with delivery of propionate to the human colon by comprehensive and coordinated analysis of gut bacterial composition, plasma metabolome and immune responses. DESIGN: Twelve non-diabetic adults with overweight and obesity received 20 g/day of inulin-propionate ester (IPE), designed to selectively deliver propionate to the colon, a high-fermentable fibre control (inulin) and a low-fermentable fibre control (cellulose) in a randomised, double-blind, placebo-controlled, cross-over design. Outcome measurements of metabolic responses, inflammatory markers and gut bacterial composition were analysed at the end of each 42-day supplementation period. RESULTS: Both IPE and inulin supplementation improved insulin resistance compared with cellulose supplementation, measured by homeostatic model assessment 2 (mean±SEM 1.23±0.17 IPE vs 1.59±0.17 cellulose, p=0.001; 1.17±0.15 inulin vs 1.59±0.17 cellulose, p=0.009), with no differences between IPE and inulin (p=0.272). Fasting insulin was only associated positively with plasma tyrosine and negatively with plasma glycine following inulin supplementation. IPE supplementation decreased proinflammatory interleukin-8 levels compared with cellulose, while inulin had no impact on the systemic inflammatory markers studied. Inulin promoted changes in gut bacterial populations at the class level (increased Actinobacteria and decreased Clostridia) and order level (decreased Clostridiales) compared with cellulose, with small differences at the species level observed between IPE and cellulose. CONCLUSION: These data demonstrate a distinctive physiological impact of raising colonic propionate delivery in humans, as improvements in insulin sensitivity promoted by IPE and inulin were accompanied with different effects on the plasma metabolome, gut bacterial populations and markers of systemic in
McPhail MJW, Trovato F, Triantafyllou E, et al., 2019, Autotaxin mediates lipid dysregulation in acute-on-chronic liver failure, promoting persistence of systemic inflammation via lysophosphatidic acid-mediated monocyte activation, International Liver Congress, Publisher: ELSEVIER SCIENCE BV, Pages: E91-E92, ISSN: 0168-8278
Tyson LD, Atkinson S, Pechlivanis A, et al., 2019, PS-174-Serum bile acid profiles distinguish severe alcoholic hepatitis from decompensated alcohol-related cirrhosis, Publisher: Elsevier BV, Pages: e108-e108, ISSN: 0168-8278
Alsaleh M, Barbera TA, Reeves HL, et al., Characterisation of urinary metabolic profiles of cholangiocarcinoma in a United Kingdom population, Hepatic Medicine : Evidence and Research, ISSN: 1179-1535
Background Outside South-East Asia, most cases of cholangiocarcinoma have an obscure aetiology. There is often diagnostic uncertainty. Metabolomics using ultraperformance liquid chromatography mass spectrometry (UPLC-MS) offers the portent to distinguish disease-specific metabolic signatures. We aimed to define such a urinary metabolic signature in a patient cohort with sporadic cholangiocarcinoma and investigate whether there were characteristic differences from those in patients with hepatocellular carcinoma, metastatic secondary liver cancer, pancreatic and ovarian cancer.Methods Spot urine specimens were obtained from 211 subjects in seven participating centres across the UK. Samples were collected from healthy controls and from patients with benign hepatic disease (gallstone, biliary strictures, sphincter of Oddi dysfunction and viral hepatitis) and patients with malignant conditions (hepatocellular carcinoma, pancreatic cancer, ovarian cancer and metastatic cancer in the liver). The spectral metabolite proﬁles were generated using a UPLC-MS detector and data were analysed using multivariate and univariate statistical analyses.Results The greatest class differences were seen between the metabolic proﬁles of disease-free controls compared to individuals with cholangiocarcinoma with altered acylcarnitine, bile acid and purine levels. Individuals with benign strictures showed comparable urine proﬁles to patients with malignant bile duct lesions. The metabolic signatures of patients with bile duct tumours were distinguishable from patients with hepatocellular and ovarian tumours, but no difference was observed between CCA cases and patients with pancreatic cancer or hepatic secondary metastases.Conclusion Cholangiocarcinoma causes subtle but detectable changes in the urine metabolic proﬁles. The ﬁndings point towards potential applications of metabonomics in early tumour detection. However, it is key to utilize both global and targeted metabonomics in a larger co
Tzoulaki I, Karaman I, Dehghan A, et al., Serum metabolic signatures of coronary and carotid atherosclerosis and subsequent cardiovascular disease, European Heart Journal, ISSN: 1522-9645
Aims: To characterise serum metabolic signatures associated with atherosclerosis in the coronary or carotid arteries and subsequently their association with incident cardiovascular disease (CVD). Methods and Results: We used untargeted one-dimensional (1D) serum metabolic profiling by proton (1H) nuclear magnetic resonance (NMR) spectroscopy among 3,867 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), with replication among 3,569 participants from the Rotterdam and LOLIPOP Studies. Atherosclerosis was assessed by coronary artery calcium (CAC) and carotid intima-media thickness (IMT). We used multivariable linear regression to evaluate associations between NMR features and atherosclerosis accounting for multiplicity of comparisons. We then examined associations between metabolites associated with atherosclerosis and incident CVD available in MESA and Rotterdam and explored molecular networks through bioinformatics analyses. Overall, 30 NMR measured metabolites were associated with CAC and/or IMT, P =1.3x10-14 to 6.5x10-6 (discovery), P =4.2x10-14 to 4.4x10-2 (replication). These associations were substantially attenuated after adjustment for conventional cardiovascular risk factors. Metabolites associated with atherosclerosis revealed disturbances in lipid and carbohydrate metabolism, branched-chain and aromatic amino acid metabolism, as well as oxidative stress and inflammatory pathways. Analyses of incident CVD events showed inverse associations with creatine, creatinine and phenylalanine, and direct associations with mannose, acetaminophen-glucuronide and lactate as well as apolipoprotein B (P <0.05). Conclusion: Metabolites associated with atherosclerosis were largely consistent between the two vascular beds (coronary and carotid arteries) and predominantly tag pathways that overlap with the known cardiovascular risk factors. We present an integrated systems network that highlights a series of inter-connected pathways underlying atherosclero
Mullish BH, McDonald JAK, Pechlivanis A, et al., 2019, Microbial bile salt hydrolases mediate the efficacy of faecal microbiota transplant in the treatment of recurrent Clostridioides difficile infection., Gut
OBJECTIVE: Faecal microbiota transplant (FMT) effectively treats recurrent Clostridioides difficile infection (rCDI), but its mechanisms of action remain poorly defined. Certain bile acids affect C. difficile germination or vegetative growth. We hypothesised that loss of gut microbiota-derived bile salt hydrolases (BSHs) predisposes to CDI by perturbing gut bile metabolism, and that BSH restitution is a key mediator of FMT's efficacy in treating the condition. DESIGN: Using stool collected from patients and donors pre-FMT/post-FMT for rCDI, we performed 16S rRNA gene sequencing, ultra performance liquid chromatography mass spectrometry (UPLC-MS) bile acid profiling, BSH activity measurement, and qPCR of bsh/baiCD genes involved in bile metabolism. Human data were validated in C. difficile batch cultures and a C57BL/6 mouse model of rCDI. RESULTS: From metataxonomics, pre-FMT stool demonstrated a reduced proportion of BSH-producing bacterial species compared with donors/post-FMT. Pre-FMT stool was enriched in taurocholic acid (TCA, a potent C. difficile germinant); TCA levels negatively correlated with key bacterial genera containing BSH-producing organisms. Post-FMT samples demonstrated recovered BSH activity and bsh/baiCD gene copy number compared with pretreatment (p<0.05). In batch cultures, supernatant from engineered bsh-expressing E. coli and naturally BSH-producing organisms (Bacteroides ovatus, Collinsella aerofaciens, Bacteroides vulgatus and Blautia obeum) reduced TCA-mediated C. difficile germination relative to culture supernatant of wild-type (BSH-negative) E. coli. C. difficile total viable counts were ~70% reduced in an rCDI mouse model after administration of E. coli expressing highly active BSH relative to mice administered BSH-negative E. coli (p<0.05). CONCLUSION: Restoration of gut BSH functionality contributes to the efficacy of FMT in treating rCDI.
Boulange CL, Rood IM, Posma JM, et al., 2019, NMR and MS urinary metabolic phenotyping in kidney diseases is fit-for-purpose in the presence of a protease inhibitor, MOLECULAR OMICS, Vol: 15, Pages: 39-49
Posma JM, 2019, Multivariate Statistical Methods for Metabolic Phenotyping, The Handbook of Metabolic Phenotyping, Publisher: Elsevier, Pages: 261-308, ISBN: 9780128122938
Adesina-Georgiadis KN, Gray N, Plumb RS, et al., 2018, The metabolic fate and effects of 2-Bromophenol in male Sprague-Dawley rats., Xenobiotica, Pages: 1-8
1. The metabolic fate and urinary excretion of 2-bromophenol, a phenolic metabolite of bromobenzene, was investigated in male Sprague-Dawley rats following single intraperitoneal doses at either 0, 100, or 200 mg/kg. 2. Urine was collected for seven days and samples analysed using 1 H NMR spectroscopy, inductively coupled plasma (ICP)MS, and UPLC-MS. 3. 1 H NMR spectroscopy of the urine samples showed that, at these doses, 2-bromophenol had little effect on endogenous metabolite profiles, supporting histopathology and clinical chemistry data, which showed no changes associated with the administration of 2-bromophenol in this study. 4. The use of ICP-MS provided a means for the selective detection and quantification of bromine-containing species and showed that between 15 and 30% of the dose was excreted via the urine over 7 days of the study for both the 100 and 200 mg doses, respectively. 5. The bulk of the excretion of Br-containing material had occurred by 8 h post administration. UPLC-MS of urine revealed a number of metabolites of 2-bromophenol, with 2-bromophenol glucuronide and 2-bromophenol sulphate identified as the major species. A number of minor hydroxylated metabolites were also detected as their glucuronide, sulphate, or O-methyl conjugates. There was no evidence for the production of reactive metabolites.
Gibson R, Lau C-H, Loo RL, et al., American Heart Association's Epidemiology and Prevention/Lifestyle and Cardiometabolic Health 2019 Scientific Sessions, American Heart Association EpiLifestyle
Izzi-Engbeaya C, Comninos AN, Clarke SA, et al., 2018, The effects of kisspeptin on beta-cell function, serum metabolites and appetite in humans, DIABETES OBESITY & METABOLISM, Vol: 20, Pages: 2800-2810, ISSN: 1462-8902
McDonald JAK, Mullish BH, Pechlivanis A, et al., 2018, Inhibiting Growth of Clostridioides difficile by Restoring Valerate, Produced by the Intestinal Microbiota, GASTROENTEROLOGY, Vol: 155, Pages: 1495-+, ISSN: 0016-5085
Jimenez B, Holmes E, Heude C, et al., 2018, Quantitative Lipoprotein Subclass and Low Molecular Weight Metabolite Analysis in Human Serum and Plasma by H-1 NMR Spectroscopy in a Multilaboratory Trial, ANALYTICAL CHEMISTRY, Vol: 90, Pages: 11962-11971, ISSN: 0003-2700
Antcliffe DB, Wolfer AM, O'Dea KP, et al., 2018, Profiling inflammatory markers in patients with pneumonia on intensive care, SCIENTIFIC REPORTS, Vol: 8, ISSN: 2045-2322
Chekmeneva E, Correia GDS, Gomez-Romero M, et al., 2018, Ultra-Performance Liquid Chromatography High-Resolution Mass Spectrometry and Direct Infusion-High-Resolution Mass Spectrometry for Combined Exploratory and Targeted Metabolic Profiling of Human Urine, JOURNAL OF PROTEOME RESEARCH, Vol: 17, Pages: 3492-3502, ISSN: 1535-3893
Puthucheary ZA, Astin R, Mcphail MJW, et al., 2018, Metabolic phenotype of skeletal muscle in early critical illness, THORAX, Vol: 73, Pages: 926-935, ISSN: 0040-6376
Hoyles L, Fernandez-Real J-M, Federici M, et al., 2018, Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women (vol 24, pg 1070, 2018), NATURE MEDICINE, Vol: 24, Pages: 1628-1628, ISSN: 1078-8956
Byrne CS, Preston T, Brignardello J, et al., 2018, The effect of L-rhamnose on intestinal transit time, short chain fatty acids and appetite regulation: a pilot human study using combined (CO2)-C-13/H-2 breath tests, JOURNAL OF BREATH RESEARCH, Vol: 12, ISSN: 1752-7155
Liu Z, Xia B, Saric J, et al., 2018, Effects of Vancomycin and Ciprofloxacin on the NMRI Mouse Metabolism, JOURNAL OF PROTEOME RESEARCH, Vol: 17, Pages: 3565-3573, ISSN: 1535-3893
Abellona MRU, Mark P, Ladep N, et al., 2018, Elucidating Serum and Urinary Hepatocellular Carcinoma Diagnostic Biomarker Panels: Insight from the United Kingdom and West Africa, Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) / Liver Meeting, Publisher: WILEY, Pages: 37A-38A, ISSN: 0270-9139
Hoyles L, Fernandez-Real J-M, Federici M, et al., 2018, Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women, NATURE MEDICINE, Vol: 24, Pages: 1070-+, ISSN: 1078-8956
Patiny L, Zasso M, Kostro D, et al., 2018, The C6H6 NMR repository: An integral solution to control the flow of your data from the magnet to the public, MAGNETIC RESONANCE IN CHEMISTRY, Vol: 56, Pages: 520-528, ISSN: 0749-1581
McDonald JAK, Kimhofer T, West K, et al., Role of the gut microbiota in autism spectrum disorder, ISME17, Publisher: Nature Publishing Group
McDonald JAK, Mullish BH, Pechlivanis A, et al., 2018, 0503 - A novel route for controlling Clostridioides difficile growth via bile acid and short chain fatty acid modulation, ISME17
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