Publications
742 results found
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: 1495-1507.e15, ISSN: 0016-5085
Background & AimsFecal microbiota transplantation (FMT) is effective for treating recurrent Clostridioides difficile infection (CDI), but there are concerns about its long-term safety. Understanding the mechanisms of the effects of FMT could help us design safer, targeted therapies. We aimed to identify microbial metabolites that are important for C difficile growth.MethodsWe used a CDI chemostat model as a tool to study the effects of FMT in vitro. The following analyses were performed: C difficile plate counts, 16S rRNA gene sequencing, 1H-NMR spectroscopy, and UPLC mass spectrometry bile acid profiling. FMT mixtures were prepared using fresh fecal samples provided by donors enrolled in an FMT program in the United Kingdom. Results from chemostat experiments were validated using human stool samples, C difficile batch cultures, and C57BL/6 mice with CDI. Human stool samples were collected from 16 patients with recurrent CDI and healthy donors (n=5) participating in an FMT trial in Canada.ResultsIn the CDI chemostat model, clindamycin decreased valerate and deoxycholic acid concentrations and increased C difficile total viable counts (TVC) and valerate precursors, taurocholic acid, and succinate concentrations. After we stopped adding clindamycin, levels of bile acids and succinate recovered, whereas levels of valerate and valerate precursors did not. In the CDI chemostat model, FMT increased valerate concentrations and decreased C difficile TVC (94% reduction), spore counts (86% reduction), and valerate precursor concentrations—concentrations of bile acids were unchanged. In stool samples from patients with CDI, valerate was depleted before FMT, but restored after FMT. C difficile batch cultures confirmed that valerate decreased vegetative growth, and that taurocholic acid is required for germination but had no effect on vegetative growth. C difficile TVC were decreased by 95% in mice with CDI given glycerol trivalerate compared to phosphate-buffered sali
Jimenez B, Holmes E, Heude C, et al., 2018, Quantitative lipoprotein subclass and low molecular weight metabolite analysis in human serum and plasma by 1H NMR spectroscopy in a multilaboratory trial, Analytical Chemistry, Vol: 90, Pages: 11962-11971, ISSN: 0003-2700
We report an extensive 600 MHz NMR trial of a quantitative lipoprotein and small molecule measurements in human blood serum and plasma. Five centers with eleven 600 MHz NMR spectrometers were used to analyze 98 samples including: 20 QCs, 37 commercially sourced, paired serum and plasma samples and 2 National Institute of Science and Technology, NIST, reference material 1951c replicates. Samples were analyzed using rigorous protocols for sample preparation and experimental acquisition. A commercial lipoprotein subclass analysis was used to quantify 105 lipoprotein subclasses and 24 low molecular weight metabolites from the nuclear magnetic resonance, NMR, spectra. For all spectrometers, the instrument specific variance in measuring internal quality controls, QCs, was lower than the percentage described by the National Cholesterol Education Program, NCEP, criteria for lipid testing (triglycerides<2.7%, cholesterol<2.8%; LDL-cholesterol<2.8%; HDL-cholesterol<2.3%), showing exceptional reproducibility for direct quantitation of lipoproteins in both matrices. The average RSD for the 105 lipoprotein parameters in the 11 instruments was 4.6% and 3.9% for the two NIST samples while it was 38% and 40% for the 37 commercially sourced plasmas and sera, respectively, showing negligible analytical compared to biological variation. The coefficient of variance, CV, obtained for the quantification of the small molecules across the 11 spectrometers was below 15% for 20 out of the 24 metabolites analyzed. This study provides further evidence of the suitability of NMR for high-throughput lipoprotein subcomponent analysis and small molecule quantitation with the exceptional reproducibility required for clinical and other regulatory settings.
Byrne CS, Preston T, Brignardello J, et al., 2018, The effect of L-rhamnose on gastrointestinal transit rates, short chain fatty acids and appetite regulation, Summer Meeting, Publisher: Cambridge University Press, Pages: E155-E155, ISSN: 0029-6651
Chekmeneva E, Dos Santos Correia G, 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
The application of metabolic phenotyping to epidemiological studies involving thousands of biofluid samples presents a challenge for the selection of analytical platforms that meet the requirements of high-throughput precision analysis and cost-effectiveness. Here, direct infusion nanoelectrospray (DI-nESI)- was compared to an ultra-performance (UPLC)-high resolution mass spectrometry (HRMS) method for metabolic profiling of an exemplary set of 132 human urine samples from a large epidemiological cohort. Both methods were developed and optimised to allow simultaneous collection of high resolution urinary metabolic profiles and quantitative data for a selected panel of 35 metabolites. The total run time for measuring the sample set in both polarities by UPLC-HRMS was of 5 days compared to 9 hours by DI-nESI-HRMS. To compare the classification ability of the two MS methods we performed exploratory analysis of the full-scan HRMS profiles to detect sex-related differences in biochemical composition. Although metabolite identification is less specific in DI-nESI-HRMS, the significant features responsible for discrimination between sexes were mostly the same in both MS-based platforms. Using the quantitative data we showed that 10 metabolites have strong correlation (Pearson’s r > 0.9 and Passing-Bablok regression slope 0.8-1.3) and good agreement assessed by Bland-Altman plots between UPLC-HRMS and DI-nESI-HRMS and thus, can be measured using a cheaper and less sample- and time-consuming method. Only five metabolites showed weak correlation (Pearson’s r< 0.4) and poor agreement due to the overestimation of the results by DI-nESI-HRMS, and the rest of metabolites showed acceptable correlation between the two methods.
Antcliffe D, Wolfer A, O'Dea K, et al., 2018, Profiling inflammatory markers in patients with pneumonia on intensive care, Scientific Reports, Vol: 8, ISSN: 2045-2322
Clinical investigations lack predictive value when diagnosing pneumonia, especially when patients are ventilated and develop ventilator associated pneumonia (VAP). New tools to aid diagnosis are important to improve outcomes. This pilot study examines the potential for a panel of inflammatory mediators to aid in the diagnosis. Forty-four ventilated patients, 17 with pneumonia and 27 with brain injuries, eight of whom developed VAP, were recruited. 51 inflammatory mediators, including cytokines and oxylipins, were measured in patients’ serum using flow cytometry and mass spectrometry. The mediators could separate patients admitted to ICU with pneumonia compared to brain injury with an area under the receiver operating characteristic curve (AUROC) 0.75 (0.61–0.90). Changes in inflammatory mediators were similar in both groups over the course of ICU stay with 5,6-dihydroxyeicosatrienoic and 8,9-dihydroxyeicosatrienoic acids increasing over time and interleukin-6 decreasing. However, brain injured patients who developed VAP maintained inflammatory profiles similar to those at admission. A multivariate model containing 5,6-dihydroxyeicosatrienoic acid, 8,9-dihydroxyeicosatrienoic acid, intercellular adhesion molecule-1, interleukin-6, and interleukin-8, could differentiate patients with VAP from brain injured patients without infection (AUROC 0.94 (0.80–1.00)). The use of a selected group of markers showed promise to aid the diagnosis of VAP especially when combined with clinical data.
Hoyles L, Fernandez-Real J-M, Federici M, et al., 2018, Publisher Correction: Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women, Nature Medicine, Vol: 24, Pages: 1628-1628, ISSN: 1078-8956
In the version of this article originally published, the received date was missing. It should have been listed as 2 January 2018. The error has been corrected in the HTML and PDF versions of this article.
Byrne C, 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 13CO2 / H2 breath tests, Journal of Breath Research, Vol: 12, ISSN: 1752-7155
Background: The appetite-regulating effects of non-digestible carbohydrates (NDC) have in part previously been attributed to their effects on intestinal transit rates as well as microbial production of short chain fatty acids (SCFA). Increased colonic production of the SCFA propionate has been shown to reduce energy intake and stimulate gut hormone secretion acutely in humans. Objective: We investigated the effect of the propiogenic NDC, L-rhamnose, on gastrointestinal transit times using a combined 13CO2/H2 breath test. We hypothesised that L-rhamnose would increase plasma propionate leading to a reduction in appetite, independent of changes in gastrointestinal transit times.Design: We used a dual 13C-octanoic acid/lactose 13C-ureide breath test combined with breath H2 to measure intestinal transit times following the consumption of 25g/d L-rhamnose, compared with inulin and cellulose, in 10 healthy humans in a randomised cross-over design pilot study. Gastric emptying (GE) and oro-caecal transit times (OCTT) were derived from the breath 13C data and compared with breath H2. Plasma SCFA and peptide YY (PYY) were also measured alongside subjective measures of appetite. Results: L-rhamnose significantly slowed GE rates (by 19.5min) but there was no difference in OCTT between treatments. However, breath H2 indicated fermentation of L-rhamnose before it reached the caecum. OCTT was highly correlated with breath H2 for inulin but not for L-rhamnose or cellulose. L-rhamnose consumption significantly increased plasma propionate and PYY but did not significantly reduce subjective appetite measures. Conclusions: The NDCs tested had a minimal effect on intestinal transit time. Our data suggest that L-rhamnose is partially fermented in the small intestine and that breath H2 reflects the site of gastrointestinal fermentation and is only a reliable marker of OCTT for certain NDCs (e.g. inulin). Future studies should focus on investigating the appetite-suppressing potential of L
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
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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
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- Citations: 95
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
The reduction in gut microbiota diversity is associated with a range of human diseases. Overuse of antibiotics has been associated with a diminished gut-microbial diversity in humans and may promote microbiota-associated negative effects to physical health, such as the metabolic syndrome-cluster of diseases and mental illnesses. There is a pressing need to deepen the understanding of the effects of antibiotics at the biochemical level. The current study investigated metabolic effects of two widely prescribed antibiotics–vancomycin and ciprofloxacin–on biofluids and brain tissue samples of NMRI female mice using a 1H nuclear magnetic resonance (NMR) spectroscopy-based metabolic profiling approach. While both antibiotics significantly affected the host metabolic signatures of urine and feces, only ciprofloxacin induced metabolic changes in plasma. Metabolic perturbations were pronounced 1 day post-treatment, reverting back to baseline at day 20 post-treatment. Both antibiotics induced changes in the choline metabolism, host-microbial cometabolites, short chain fatty acid production, and protein/purine degradation. The metabolic profiles of brain tissue aqueous extracts did not show any antibiotics-related changes by day 20 post-treatment. The data suggest that the metabolic disruptions in biofluids caused by antibiotics are reversed by day 20 post-treatment when compared to the pre-treatment profiles.
Walsh K, Calder N, Olupot-Olupot P, et al., 2018, Modifying Intestinal Integrity and Micro Biome in Severe Malnutrition with Legume-Based Feeds (MIMBLE 2.0): protocol for a phase II refined feed and intervention trial [version 1; referees: 2 approved], Wellcome Open Research, Vol: 3, Pages: 95-95, ISSN: 2398-502X
Background: Changes in intestinal mucosal integrity and gut microbial balance occur in severe acute malnutrition (SAM), resulting in treatment failure and adverse clinical outcomes (gram-negative sepsis, diarrhoea and high case-fatality). Transient lactose intolerance, due to loss of intestinal brush border lactase, also complicates SAM, thus milk based feeds may not be optimal for nutritional rehabilitation. Since the gut epithelial barrier can be supported by short chain fatty acids, derived from microbiota fermentation by particular fermentable carbohydrates, we postulated that an energy-dense nutritional feed comprising of legume-based fermentable carbohydrates, incorporated with lactose-free versions of standard World Health Organization (WHO) F75/F100 nutritional feeds will enhance epithelial barrier function in malnourished children, reduce and promote resolution of diarrhoea and improve overall outcome. Methods: We will investigate in an open-label trial in 160 Ugandan children with SAM, defined by mid-upper arm circumference <11.5cm and/or presence of kwashiorkor. Children will be randomised to a lactose-free, chickpea-enriched feed containing 2 kcal/ml, provided in quantities to match usual energy provision (experimental) or WHO standard treatment F75 (0.75 kcal/ml) and F100 (1 kcal/ml) feeds on a 1:1 basis, conducted at Mbale Regional Referral Hospital nutritional rehabilitation unit. The primary outcomes are change in MUAC at day 90 and survival to day 90. Secondary outcomes include: i) moderate to good weight gain (>5 g/kg/day), ii) de novo development of diarrhoea (>3 loose stools/day), iii) time to diarrhoea resolution (if >3 loose stools/day), and iv) time to oedema resolution (if kwashiorkor) and change in intestinal biomarkers (faecal calprotectin). Discussion: We hypothesize that, if introduced early in the management of malnutrition, such lactose-free, fermentable carbohydrate-based feeds, could safely and cheaply improve global outco
Walsh K, Calder N, Olupot-Olupot P, et al., 2018, Modifying Intestinal Integrity and MicroBiome in Severe Malnutrition with Legume-Based Feeds (MIMBLE 2.0): protocol for a phase II refined feed and intervention trial, Wellcome Open Research, Vol: 3, ISSN: 2398-502X
Background: Changes in intestinal mucosal integrity and gut microbial balance occur in severe acute malnutrition (SAM), resulting in treatment failure and adverse clinical outcomes (gram-negative sepsis, diarrhoea and high case-fatality). Transient lactose intolerance, due to loss of intestinal brush border lactase, also complicates SAM, thus milk based feeds may not be optimal for nutritional rehabilitation. Since the gut epithelial barrier can be supported by short chain fatty acids, derived from microbiota fermentation by particular fermentable carbohydrates, we postulated that an energy-dense nutritional feed comprising of legume-based fermentable carbohydrates, incorporated with lactose-free versions of standard World Health Organization (WHO) F75/F100 nutritional feeds will enhance epithelial barrier function in malnourished children, reduce and promote resolution of diarrhoea and improve overall outcome. Methods: We will investigate in an open-label trial in 160 Ugandan children with SAM, defined by mid-upper arm circumference <11.5cm and/or presence of kwashiorkor. Children will be randomised to a lactose-free, chickpea-enriched feed containing 2 kcal/ml, provided in quantities to match usual energy provision (experimental) or WHO standard treatment F75 (0.75 kcal/ml) and F100 (1 kcal/ml) feeds on a 1:1 basis, conducted at Mbale Regional Referral Hospital nutritional rehabilitation unit. The primary outcomes are change in MUAC at day 90 and survival to day 90. Secondary outcomes include: i) moderate to good weight gain (>5 g/kg/day), ii) de novo development of diarrhoea (>3 loose stools/day), iii) time to diarrhoea resolution (if >3 loose stools/day), and iv) time to oedema resolution (if kwashiorkor) and change in intestinal biomarkers (faecal calprotectin). Discussion: We hypothesize that, if introduced early in the management of malnutrition, such lactose-free, fermentable carbohydrate-based feeds, could safely and cheaply improve global outco
Posma JM, 2018, Multivariate statistical methods for metabolic phenotyping, The Handbook of Metabolic Phenotyping, Editors: Lindon, Holmes, Nicholson, Publisher: Elsevier
The nature of metabolic phenotyping data, where typically more variables are measured than samples are available, requires careful application of statistical methods in order to be able to make meaningful inferences from the data. This Chapter describes different aspects of the multivariate modelling of this type of data, including data transformations and partitioning, unsupervised algorithms for dimension reduction, supervised algorithms for classification, clustering and regression, metrics and methods for obtaining unbiased prediction error estimates of predictive models and statistical spectroscopy tools used for biomarker identification. It focusses on describing methods routinely applied in the field as well as discussing methods that, as computational advancements are made, are poised to become more widely applied to metabolic phenotyping data.
Hoyles L, Fernández-Real JM, Federici M, et al., 2018, Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women, Nature Medicine, Vol: 24, Pages: 1-17, ISSN: 1078-8956
Hepatic steatosis is a multifactorial condition that is often observed in obese patients and is a prelude to non-alcoholic fatty liver disease. Here, we combine shotgun sequencing of fecal metagenomes with molecular phenomics (hepatic transcriptome and plasma and urine metabolomes) in two well-characterized cohorts of morbidly obese women recruited to the FLORINASH study. We reveal molecular networks linking the gut microbiome and the host phenome to hepatic steatosis. Patients with steatosis have low microbial gene richness and increased genetic potential for the processing of dietary lipids and endotoxin biosynthesis (notably from Proteobacteria), hepatic inflammation and dysregulation of aromatic and branched-chain amino acid metabolism. We demonstrated that fecal microbiota transplants and chronic treatment with phenylacetic acid, a microbial product of aromatic amino acid metabolism, successfully trigger steatosis and branched-chain amino acid metabolism. Molecular phenomic signatures were predictive (area under the curve = 87%) and consistent with the gut microbiome having an effect on the steatosis phenome (>75% shared variation) and, therefore, actionable via microbiome-based therapies.
Seow WJ, Shu X-O, Nicholson J, et al., 2018, Prospective study of untargeted urinary metabolomics and risk of lung cancer among female never-smokers in Shanghai, China, Annual Meeting of the American-Association-for-Cancer-Research (AACR), Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
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Qureshi M, Kaluarachchi M, Vorkas P, et al., 2018, Metabolic Profiling of High-Risk Carotid Atherosclerosis, Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS), Publisher: MOSBY-ELSEVIER, Pages: E236-E236, ISSN: 0741-5214
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
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- Citations: 13
Alkandari A, Ashrafian H, Sathyapalan T, et al., 2018, Improved physiology and metabolic flux after Roux-en-Y gastric bypass is associated with temporal changes in the circulating microRNAome: a longitudinal study in humans., BMC Obesity, Vol: 5, ISSN: 2052-9538
BackgroundThe global pandemic of obesity and the metabolic syndrome are leading causes of mortality and morbidity. Bariatric surgery leads to sustained weight loss and improves obesity-associated morbidity including remission of type 2 diabetes. MicroRNAs are small, endogenous RNAs that regulate gene expression post-transcriptionally, controlling most of the human transcriptome and contributing to the regulation of systemic metabolism. This preliminary, longitudinal, repeat sampling study, in which subjects acted as their own control, aimed to assess the temporal effect of bariatric surgery on circulating microRNA expression profiles.MethodsWe used Exiqon’s optimized circulating microRNA panel (comprising 179 validated miRNAs) and miRCURY locked nucleic acid plasma/serum Polymerase Chain Reaction (PCR) to assess circulating microRNA expression. The microRNAome was determined for Roux-en-Y gastric bypass (RYGB) patients examined preoperatively and at 1 month, 3 months, 6 months, 9 months and 12 months postoperatively. Data was analysed using multivariate and univariate statistics.ResultsCompared to the preoperative circulating microRNA expression profile, RYGB altered the circulating microRNAome in a time dependent manner and the expression of 48 circulating microRNAs were significantly different. Importantly, these latter microRNAs are associated with pathways involved in regulation and rescue from metabolic dysfunction and correlated with BMI, the percentage of excess weight loss and fasting blood glucose levels.ConclusionsThe results of this pilot study show that RYGB fundamentally alters microRNA expression in circulation with a time-dependent progressive departure in profile from the preoperative baseline and indicate that microRNAs are potentially novel biomarkers for the benefits of bariatric surgery.
McDonald JAK, Kimhofer T, West K, et al., 2018, Role of the gut microbiota in autism spectrum disorder, ISME17, Publisher: Nature Publishing Group
McDonald JAK, Mullish BH, Pechlivanis A, et al., 2018, A novel route for controlling Clostridioides difficile growth via bile acid and short chain fatty acid modulation, ISME17
Cronin O, Barton W, Skuse P, et al., 2018, A prospective metagenomic and metabolomic analysis of the impact of exercise and/or whey protein supplementation on the gut microbiome of sedentary adults, mSystems, Vol: 3, ISSN: 2379-5077
Many components of modern living exert influence on the resident intestinal microbiota of humans with resultant impact on host health. For example, exercise-associated changes in the diversity, composition, and functional profiles of microbial populations in the gut have been described in cross-sectional studies of habitual athletes. However, this relationship is also affected by changes in diet, such as changes in dietary and supplementary protein consumption, that coincide with exercise. To determine whether increasing physical activity and/or increased protein intake modulates gut microbial composition and function, we prospectively challenged healthy but sedentary adults with a short-term exercise regime, with and without concurrent daily whey protein consumption. Metagenomics- and metabolomics-based assessments demonstrated modest changes in gut microbial composition and function following increases in physical activity. Significant changes in the diversity of the gut virome were evident in participants receiving daily whey protein supplementation. Results indicate that improved body composition with exercise is not dependent on major changes in the diversity of microbial populations in the gut. The diverse microbial characteristics previously observed in long-term habitual athletes may be a later response to exercise and fitness improvement. IMPORTANCE The gut microbiota of humans is a critical component of functional development and subsequent health. It is important to understand the lifestyle and dietary factors that affect the gut microbiome and what impact these factors may have. Animal studies suggest that exercise can directly affect the gut microbiota, and elite athletes demonstrate unique beneficial and diverse gut microbiome characteristics. These characteristics are associated with levels of protein consumption and levels of physical activity. The results of this study show that increasing the fitness levels of physically inactive humans leads to mo
McDonald JAK, Mullish BH, Pechlivanis A, et al., 2018, 24 - A novel route to controlling Clostridioides Difficile growth via short chain fatty acid and bile acid modulation, Digestive Diseases Week, Publisher: Elsevier, Pages: S8-S8, ISSN: 0016-5085
Sung Y, Spagou K, Kafeza M, et al., 2018, Deep vein thrombosis exhibits characteristic serum and vein wall metabolic phenotypes in the inferior vena cava ligation mouse model, European Journal of Vascular and Endovascular Surgery, Vol: 55, Pages: 703-713, ISSN: 1078-5884
Deep vein thrombosis (DVT) is a major health problem, responsible for significant morbidity and mortality, and imposes a heavy economic burden to healthcare systems (1). Although most events resolve without complication through spontaneous lysis and recanalization, DVT can be complicated with life-threatening pulmonary embolism (2), while approximately one third of DVT patients develop post-thrombotic syndrome with swelling, pain, skin changes and/or venous ulceration (3).Treatment with anticoagulation prevents further thrombus extension, protects from pulmonary embolism and reduces the risk of chronic lower limb complications. Importantly, unnecessary treatment can result in bleeding. Therefore, accurate and reliable DVT diagnosis is essential. Currently, diagnosis relies on subjective clinical examination and ultrasound imaging (4). A number of biological markers have been investigated with variable results. D-dimer, the most widely used biomarker, is sensitive but lacks specificity (5, 6). Ongoing research efforts target the utility of alternative blood diagnostic biomarkers able to accurately diagnose DVT, guide length and type of treatment, and potentially identify patients who may benefit from more aggressive therapies than standard anticoagulation. New molecular technologies and methods have entered the scientific arena, offering the opportunity to revisit this important clinical need. Metabolic profiling has emerged as a new approach to investigate complex metabolic disease and enable precision medicine. Metabolomics is the comprehensive and systematic identification of the small molecules present in differential abundance in biofluids and are affected by various factors such as diet, lifestyle, genetics, disease, environmental factors and medications. Metabolic profiling approaches to characterizing the metabolome can be either targeted or untargeted. In targeted approaches specific metabolites, representative of suspected biological pathways, are analysed
Powles ST, Hicks LC, Chong LW, et al., 2018, EFFECT OF BOWEL PURGATIVES ON URINARY METABOLIC PROFILING ASSOCIATED WITH THE FAECAL MICROBIOME, Annual Meeting of the American-Society-for-Gastrointestinal-Endoscopy / Digestive Disease Week (DDW) / 59th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract (SSAT), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S860-S860, ISSN: 0016-5085
Misra R, Sarafian M, Pechlivanis A, et al., 2018, SOUTH ASIAN ETHNICITY DRIVES DIFFERENCES IN MICROBIAL AND METABOLIC PROFILING IN A NEWLY DIAGNOSED ULCERATIVE COLITIS COHORT, Annual Meeting of the American-Society-for-Gastrointestinal-Endoscopy / Digestive Disease Week, Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S33-S34, ISSN: 0016-5085
Abellona U, Mark DP, Oleribe O, et al., 2018, Towards elucidating a universal panel of diagnostic biomarkers for early hepatocellular carcinoma, International Liver Congress (ILC), Publisher: ELSEVIER SCIENCE BV, Pages: S433-S433, ISSN: 0168-8278
Nguyen VI, Cordero P, Li J, et al., 2018, The effect of intragastric balloon therapy on the intestinal microbiome in obese patients with non-alcoholic fatty liver disease, and correlations with anthropometric indices, nutritional factors, and serum immunological markers, International Liver Congress (ILC), Publisher: ELSEVIER SCIENCE BV, Pages: S59-S59, ISSN: 0168-8278
Barton W, Penney NC, Cronin O, et al., 2018, The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level, Gut, Vol: 67, Pages: 625-633, ISSN: 0017-5749
OBJECTIVE: It is evident that the gut microbiota and factors that influence its composition and activity effect human metabolic, immunological and developmental processes. We previously reported that extreme physical activity with associated dietary adaptations, such as that pursued by professional athletes, is associated with changes in faecal microbial diversity and composition relative to that of individuals with a more sedentary lifestyle. Here we address the impact of these factors on the functionality/metabolic activity of the microbiota which reveals even greater separation between exercise and a more sedentary state. DESIGN: Metabolic phenotyping and functional metagenomic analysis of the gut microbiome of professional international rugby union players (n=40) and controls (n=46) was carried out and results were correlated with lifestyle parameters and clinical measurements (eg, dietary habit and serum creatine kinase, respectively). RESULTS: Athletes had relative increases in pathways (eg, amino acid and antibiotic biosynthesis and carbohydrate metabolism) and faecal metabolites (eg, microbial produced short-chain fatty acids (SCFAs) acetate, propionate and butyrate) associated with enhanced muscle turnover (fitness) and overall health when compared with control groups. CONCLUSIONS: Differences in faecal microbiota between athletes and sedentary controls show even greater separation at the metagenomic and metabolomic than at compositional levels and provide added insight into the diet-exercise-gut microbiota paradigm.
Loo RL, Zou X, Appel LJ, et al., 2018, Characterization of metabolic responses to healthy diets and association with blood pressure: application to the Optimal Macronutrient Intake Trial for Heart Health (OmniHeart), a randomized controlled study, AMERICAN JOURNAL OF CLINICAL NUTRITION, Vol: 107, Pages: 323-334, ISSN: 0002-9165
BackgroundInterindividual variation in the response to diet is common, but the underlying mechanism for such variation is unclear.ObjectiveThe objective of this study was to use a metabolic profiling approach to identify a panel of urinary metabolites representing individuals demonstrating typical (homogeneous) metabolic responses to healthy diets, and subsequently to define the association of these metabolites with improvement of risk factors for cardiovascular diseases (CVDs).Design24-h urine samples from 158 participants with pre-hypertension and stage 1 hypertension, collected at baseline and following the consumption of a carbohydrate-rich, a protein-rich, and a monounsaturated fat–rich healthy diet (6 wk/diet) in a randomized, crossover study, were analyzed by proton (1H) nuclear magnetic resonance (NMR) spectroscopy. Urinary metabolite profiles were interrogated to identify typical and variable responses to each diet. We quantified the differences in absolute excretion of metabolites, distinguishing between dietary comparisons within the typical response groups, and established their associations with CVD risk factors using linear regression.ResultsGlobally all 3 diets induced a similar pattern of change in the urinary metabolic profiles for the majority of participants (60.1%). Diet-dependent metabolic variation was not significantly associated with total cholesterol or low-density lipoprotein (LDL) cholesterol concentration. However, blood pressure (BP) was found to be significantly associated with 6 urinary metabolites reflecting dietary intake [proline-betaine (inverse), carnitine (direct)], gut microbial co-metabolites [hippurate (direct), 4-cresyl sulfate (inverse), phenylacetylglutamine (inverse)], and tryptophan metabolism [N-methyl-2-pyridone-5-carboxamide (inverse)]. A dampened clinical response was observed in some individuals with variable metabolic responses, which could be attributed to nonadherence to diet (≤25.3%), variation in gut mi
Posma JM, Garcia Perez I, Ebbels TMD, et al., 2018, Optimized phenotypic biomarker discovery and confounder elimination via covariate-adjusted projection to latent structures from metabolic spectroscopy data, Journal of Proteome Research, Vol: 17, Pages: 1586-1595, ISSN: 1535-3893
Metabolism is altered by genetics, diet, disease status, environment and many other factors. Modelling either one of these is often done without considering the effects of the other covariates. Attributing differences in metabolic profile to one of these factors needs to be done while controlling for the metabolic influence of the rest. We describe here a data analysis framework and novel confounder-adjustment algorithm for multivariate analysis of metabolic profiling data. Using simulated data we show that similar numbers of true associations and significantly less false positives are found compared to other commonly used methods. Covariate-Adjusted Projections to Latent Structures (CA-PLS) is exemplified here using a large-scale metabolic phenotyping study of two Chinese populations at different risks for cardiovascular disease. Using CA-PLS we find that some previously reported differences are actually associated with external factors and discover a number of previously unreported biomarkers linked to different metabolic pathways. CA-PLS can be applied to any multivariate data where confounding may be an issue and the confounder-adjustment procedure is translatable to other multivariate regression techniques.
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