Publications
742 results found
Turner PJ, Garcia MR, Skypala IJ, et al., 2018, CHANGES IN METABONOMIC PROFILE DURING PEANUT-INDUCED ANAPHYLAXIS AND CORRELATION WITH SYMPTOM, American-Academy-of-Allergy-Asthma-and-Immunology / World-Allergy-Organization Joint Congress, Publisher: MOSBY-ELSEVIER, Pages: AB85-AB85, ISSN: 0091-6749
Misra R, Sarafian M, Pechilvanis A, et al., 2018, South Asian ethnicity drives differences in microbial and metabolic profiling in a newly diagnosed ulcerative colitis cohort, Publisher: OXFORD UNIV PRESS, Pages: S120-S121, ISSN: 1873-9946
MacIntyre DA, Brown R, Marchesi J, et al., 2018, Vaginal dysbiosis increases risk of preterm fetal membrane rupture, neonatal sepsis and is exacerbated by erythromycin, BMC Medicine, Vol: 16, ISSN: 1741-7015
Background: Preterm prelabour rupture of the fetal membranes (PPROM) precedes 30% of preterm births and is a risk factor for early onset neonatal sepsis. As PPROM is strongly associated with ascending vaginal infection prophylactic antibiotics are widely used. The evolution of vaginal microbiota composition associated with PPROM and the impact of antibiotics on bacterial composition is unknown. Methods: We prospectively assessed vaginal microbiota prior to and following PPROM using MiSeq-based sequencing of 16S rRNA gene amplicons and examined the impact of erythromycin prophylaxis on bacterial load and community structures.Results: In contrast to pregnancies delivering at term, vaginal dysbiosis characterised by Lactobacillus spp. depletion, was present prior to the rupture of fetal membranes in approximately a third of cases (0% versus 27%, P= 0.026) and persisted following membrane rupture (31%, P= 0.005). Vaginal dysbiosis was exacerbated by erythromycin treatment (47%, P= 0.00009) particularly in women initially colonised by Lactobacillus species. Lactobacillus depletion and increased relative abundance of Sneathia spp. was associated with subsequent funisitis and early onset neonatal sepsis. Conclusions:Our data show that vaginal microbiota composition is a risk-factor for subsequent PPROM and is associated with adverse short-term maternal and neonatal outcomes. This highlights vaginal microbiota as a potentially modifiable antenatal risk factor for PPROM and suggests that routine use of erythromycin for PPROM be re-examined.
Cobbold JFL, Atkinson S, Marchesi JR, et al., 2018, Rifaximin in non-alcoholic steatohepatitis: An open-label pilot study, HEPATOLOGY RESEARCH, Vol: 48, Pages: 69-77, ISSN: 1386-6346
AimGut microbial dysbiosis is implicated in the pathogenesis of non‐alcoholic steatohepatitis (NASH). We investigated downstream effects of gut microbiota modulation on markers of hepatic inflammation, steatosis, and hepatic and peripheral insulin sensitivity in patients with NASH using rifaximin therapy.MethodsPatients with biopsy‐proven NASH and elevated aminotransferase values were included in this open‐label pilot study, all receiving 6 weeks rifaximin 400 mg twice daily, followed by a 6‐week observation period. The primary endpoint was change in alanine aminotransferase (ALT) after 6 weeks of rifaximin. Secondary endpoints were change in hepatic lipid content and insulin sensitivity measured with a hyperinsulinemic–euglycemic clamp.ResultsFifteen patients (13 men and 2 women) with a median (range) age of 46 (32–63) years were included. Seven had diabetes on oral hypoglycemic medications and 8 had no diabetes. After 6 weeks of therapy, no differences were seen in ALT (55 [33–191] vs. 63 [41–218] IU/L, P = 0.41), peripheral glucose uptake (28.9 [19.4–48.3] to 25.5 [17.7–47.9] μmol/kg/min, P = 0.30), hepatic insulin sensitivity (35.2 [15.3–51.7]% vs. 30.0 [10.8–50.5]%, P = 0.47), or hepatic lipid content (21.6 [2.2–46.2]% vs. 24.8 [1.7–59.3]%, P = 0.59) before and after rifaximin treatment. After 12 weeks from baseline, serum ALT increased to 83 (30–217) IU/L, P = 0.02. There was a significant increase in the homeostasis model assessment–estimated insulin resistance index (P = 0.05). The urinary metabolic profile indicated a significant reduction in urinary hippurate with treatment, which reverted to baseline after cessation of rifaximin, although there was no consistent difference in relative abundance of fecal microbiota with treatment.ConclusionThese data do not indicate a beneficial effect of rifaximin i
Pathan N, Peters M, Josef W, et al., 2018, LOSS OF FECAL MICROBIAL DENSITY AND INTESTINAL FERMENTATION EFFICIENCY IN CRITICALLY ILL CHILDREN, 47th Critical Care Congress of the Society-of-Critical-Care-Medicine, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 339-339, ISSN: 0090-3493
Bracewell-Milnes T, Saso S, Abdalla H, et al., 2017, Metabolomics as a tool to identify biomarkers to predict and improve outcomes in reproductive medicine: a systematic review, Human Reproduction Update, Vol: 23, Pages: 723-736, ISSN: 1355-4786
BACKGROUNDInfertility is a complex disorder with significant medical, psychological and financial consequences for patients. With live-birth rates per cycle below 30% and a drive from the Human Fertilisation and Embryology Authority (HFEA) to encourage single embryo transfer, there is significant research in different areas aiming to improve success rates of fertility treatments. One such area is investigating the causes of infertility at a molecular level, and metabolomics techniques provide a platform for studying relevant biofluids in the reproductive tract.OBJECTIVE AND RATIONALEThe aim of this systematic review is to examine the recent findings for the potential application of metabolomics to female reproduction, specifically to the metabolomics of follicular fluid (FF), embryo culture medium (ECM) and endometrial fluid. To our knowledge no other systematic review has investigated this topic.SEARCH METHODSEnglish peer-reviewed journals on PubMed, Science Direct, SciFinder, were systematically searched for studies investigating metabolomics and the female reproductive tract with no time restriction set for publications. Studies were assessed for quality using the risk of bias assessment and ROBIN-I.OUTCOMESThere were 21 studies that met the inclusion criteria and were included in the systematic review. Metabolomic studies have been employed for the compositional analysis of various biofluids in the female reproductive tract, including FF, ECM, blastocoele fluid and endometrial fluid. There is some weak evidence that metabolomics technologies studying ECM might be able to predict the viability of individual embryos and implantation rate better than standard embryo morphology, However these data were not supported by randomized the controlled trials (RCTs) which showed no evidence that using metabolomics is able to improve the most important reproductive outcomes, such as clinical pregnancy and live-birth rates. This systematic review provides guidance for future
Parkinson JRC, Wijeyesekera A, Hyde MJ, et al., 2017, Early preterm nutrition and the urinary metabolome in young adult life; follow-up of a randomised controlled trial, BMJ Paediatrics Open, Vol: 1, ISSN: 2399-9772
Objective We aimed to test the hypothesis that early diet programmes the metabolic profile of young adults born preterm.Design We analysed banked urine samples obtained at a 20-year follow-up visit from adults that had participated as neonates in controlled trials involving randomisation within 48 hours of birth to feeds of preterm formula (PTF), banked breast milk (BBM) or term formula (TF) for 1 month postnatally.Main outcome measures We performed proton nuclear magnetic resonance spectroscopy, analysing spectra by dietary group and sex. Orthogonal projections to latent structure discriminant analyses was used to model class differences and identify metabolites contributing to the differences between groups. Additionally, spectra were correlated with birth weight, gestational age and weight z score at 2 weeks of age.Results Of the original number of 926 trial participants, urine samples were available from 197 (21%) healthy young adults (42% men) born preterm (mean 30.7±2.8 weeks) and randomised to BBM (n=55; 28 men), TF (n=48; 14 men) and PTF (n=93; 40 men). We found no significant differences in urinary spectra between dietary groups including when stratified by sex. Correlation analysis revealed a weak association between metabolic profile and gestational age that was lost on controlling for ethanol excretion.Conclusions We found no evidence that dietary exposures in the neonatal period influence the metabolic phenotype in young adult life.
Garcia Perez I, Posma JM, Gibson R, et al., 2017, Modernizing dietary assessment, IUNS 21st ICN International Congress of Nutrition, Publisher: Karger Publishers, Pages: 286-287, ISSN: 1421-9697
Hegade VS, Pechlivanis A, McDonald JA, et al., 2017, Serum Metabonomic and Gut Microbial Profile in Patients with Primary Biliary Cholangitis with Pruritus and the Effect of Ileal Bile Acid Transporter Inhibition, 68th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) / Liver Meeting, Publisher: WILEY, Pages: 171A-171A, ISSN: 0270-9139
Panic G, Keiser J, Coulibaly JT, et al., 2017, Metabolic profiling of pre-school aged and school-aged children infected with Schistosoma mansoni and treated with praziquantel, Publisher: WILEY, Pages: 107-108, ISSN: 1360-2276
Bray R, Cacciatore S, Jimenez B, et al., 2017, Urinary metabolic phenotyping of women with lower urinary tract symptoms, Journal of Proteome Research, Vol: 16, Pages: 4208-4216, ISSN: 1535-3893
Lower urinary tract symptoms (LUTS), including urinary incontinence, urgency and nocturia, affect approximately half of women worldwide. Current diagnostic methods for LUTS are invasive and costly, while available treatments are limited by side effects leading to poor patient compliance. In this study, we aimed to identify urine metabolic signatures associated with LUTS using proton nuclear magnetic resonance (1H NMR) spectroscopy. A total of 214 urine samples were collected from women attending tertiary urogynecology clinics (cases; n = 176) and healthy control women attending general gynecology clinics (n = 36). Despite high variation in the urine metabolome across the cohort, associations between urine metabolic profiles and BMI, parity, overactive bladder syndrome, frequency, straining, and bladder storage were identified using KODAMA (knowledge discovery by accuracy maximization). Four distinct urinary metabotypes were identified, one of which was associated with increased urinary frequency and low BMI. Urine from these patients was characterized by increased levels of isoleucine and decreased levels of hippurate. Our study suggests that metabolic profiling of urine samples from LUTS patients offers the potential to identify differences in underlying etiology, which may permit stratification of patient populations and the design of more personalized treatment strategies.
Ahmad MS, Kimhofer T, Ahmad S, et al., 2017, Ethnicity and skin autofluorescence-based risk-engines for cardiovascular disease and diabetes mellitus, PLoS One, Vol: 12, Pages: 1-12, ISSN: 1932-6203
Skin auto fluorescence (SAF) is used as a proxy for the accumulation of advanced glycation end products (AGEs) and has been proposed to stratify patients into cardiovascular disease (CVD) and diabetes mellitus (DM) risk groups. This study evaluates the effects of seven different ethnicities (Arab, Central-East African, Eastern Mediterranean, European, North African, South Asian and Southeast Asian) and gender on SAF as well as validating SAF assessment as a risk estimation tool for CVD and DM in an Arabian cohort. SAF data from self-reported healthy 2,780 individuals, collated from three independent studies, has been linear modelled using age and gender as a covariate. A cross-study harmonized effect size (Cohens’d) is provided for each ethnicity. Furthermore, new data has been collected from a clinically well-defined patient group of 235 individuals, to evaluate SAF as a clinical tool for DM and CVD-risk estimation in an Arab cohort. In an Arab population, SAF-based CVD and/or DM risk-estimation can be improved by referencing to ethnicity and gender-specific SAF values. Highest SAF values were observed for the North African population, followed by East Mediterranean, Arab, South Asian and European populations. The South Asian population had a slightly steeper slope in SAF values with age compared to other ethnic groups. All ethnic groups except Europeans showed a significant gender effect. When compared with a European group, effect size was highest for Eastern Mediterranean group and lowest for South Asian group. The Central-East African and Southeast Asian ethnicity matched closest to the Arab and Eastern Mediterranean ethnicities, respectively. Ethnic and gender-specific data improves performance in SAF-based CVD and DM risk estimation. The provided harmonized effect size allows a direct comparison of SAF in different ethnicities. For the first time, gender differences in SAF are described for North African and East Mediterranean populations.
Hoyles L, Fernández-Real JM, Federici M, et al., 2017, Integrated systems biology to study the contribution of the gut microbiome to steatosis in obese women, Exploring Human Host-Microbiome Interactions in Health and Disease
Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease, increasing in worldwide prevalence as a result of the obesity epidemic. It manifests in hepatic cells as steatosis with or without lobular inflammation and/or ballooning. Animal and human studies have suggested the gut microbiome contributes to steatosis/NAFLD. The aim of this study was to use an integrated approach with various -omics and clinical data to evaluate the contribution of the gut microbiome to the molecular phenome (hepatic transcriptome, metabonome) of steatosis. Metagenomic (faecal microbiome), transcriptomic (liver biopsy), metabonomic (plasma and urine, 1H-NMR) and clinical data were collected for 56 morbidly obese (BMI >35) women from Italy (n = 31) and Spain (n = 25) who elected for bariatric surgery. Confounder analyses of clinical data were done using linear modelling. Histological examination of liver biopsies was used to grade steatosis. Faecal metagenomes were generated and analysed using the SCalable Automated Metagenomics Pipeline (SCAMP). Differentially expressed genes were identified in hepatic transcriptomes, and analysed using a range of different bioinformatics tools. 1H-NMR data were generated for plasma and urinary metabonomes. Clinical, metagenomic, transcriptomic and metabonomic data were integrated in the context of steatosis using partial Spearman's correlation, taking confounders (age, body mass index and cohort) into account. Steatosis was anti-correlated with microbial gene richness, and correlated with abundance of Proteobacteria. KEGG analyses of metagenomic data suggested increased microbial processing of dietary lipids and amino acids, as well as endotoxin-related processes related to Proteobacteria. Steatosis-associated hepatic transcriptomes were associated with branched-chain amino acid (BCAA) metabolism, endoplasmic reticulum/phagosome, and immune responses associated with non-specific microbial infections. Metabonom
Lamour SD, Alibu VP, Holmes E, et al., 2017, Metabolic Profiling of Central Nervous System Disease in Trypanosoma brucei rhodesiense infection, Journal of Infectious Diseases, Vol: 216, Pages: 1273-1280, ISSN: 0022-1899
BACKGROUND: The progression of Human African Trypanosomiasis from the early hemolymphatic stage to the late meningoencephalitic stage is of critical diagnostic importance as it determines the choice of potentially toxic drug regimens. Current diagnostic criteria involving analysis of cerebrospinal fluid (CSF) for parasites and/or pleiocytosis are sensitive, but recent evidence suggests that specificity may be poor.METHODS: We used an untargeted global metabolic profiling approach for the discovery of novel candidate stage diagnostic markers in CSF from Trypanosoma brucei rhodesiense patients using 1H nuclear magnetic resonance (NMR) spectroscopy.RESULTS: Metabolic markers did not resolve early and late stage cases but were associated with neuro-inflammatory responses and the presentation of neurological disturbances. In particular increased 3-hydroxybutyrate and alanine and reduced concentrations of mannose and urea were discriminatory for the presentation of daytime somnolence and gait ataxia.CONCLUSIONS: CSF metabolite concentrations provide markers for neuroinflammatory responses during CNS invasion by trypanosomes and are associated with the presentation of neurological disturbances independently of disease stage determined by current criteria. This suggests that applying a dichotomous stage diagnosis on the basis of CSF pleiocytosis does not accurately reflect the biological changes occurring as parasites invade the CNS and has implications for biomarker discovery strategies.
Lewis MC, Merrifield CA, Berger B, et al., 2017, Early intervention with Bifidobacterium lactis NCC2818 modulates the host-microbe interface independent of the sustained changes induced by the neonatal environment., Scientific Reports, Vol: 7, ISSN: 2045-2322
Inflammatory and metabolic diseases can originate during early-life and have been correlated with shifts in intestinal microbial ecology. Here we demonstrate that minor environmental fluctuations during the early neonatal period had sustained effects on the developing porcine microbiota and host-microbe interface. These inter-replicate effects appear to originate during the first day of life, and are likely to reflect very early microbiota acquisition from the environment. We statistically link early systemic inflammation with later local increases in inflammatory cytokine (IL-17) production, which could have important enteric health implications. Immunity, intestinal barrier function, host metabolism and host-microbiota co-metabolism were further modified by Bifidobacterium lactis NCC2818 supplementation, although composition of the in situ microbiota remained unchanged. Finally, our robust model identified novel, strong correlations between urinary metabolites (eg malonate, phenylacetylglycine, alanine) and mucosal immunoglobulin (IgM) and cytokine (IL-10, IL-4) production, thus providing the possibility of the development of urinary 'dipstick' tests to assess non-accessible mucosal immune development and identify early precursors (biomarkers) of disease. These results have important implications for infants exposed to neonatal factors including caesarean delivery, antibiotic therapy and delayed discharge from hospital environments, which may predispose to the development of inflammatory and metabolic diseases in later life.
Hicks LC, Powles STR, Chong LWL, et al., 2017, EFFECTS OF TIME ON URINARY METABOLIC SIGNATURES IN INFLAMMATORY BOWEL DISEASE, Annual General Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A233-A234, ISSN: 0017-5749
Hicks LC, Powles STR, Chong LWL, et al., 2017, ASSESSING THE EFFECT OF ETHNICITY ON URINARY METABOLIC PROFILES IN INFLAMMATORY BOWEL DISEASE, Annual General Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A261-A262, ISSN: 0017-5749
Hoyles L, Fernández-Real JM, Federici M, et al., 2017, Integrated systems biology to study non-alcoholic fatty liver disease in obese women, International Scientific Association for Probiotics and Prebiotics
Metagenomic (faecal microbiome), transcriptomic (liver biopsy), metabonomic (plasma and urine, 1H-NMR) and clinical (28 variables) data were collected for 56 morbidly obese (BMI >35) women from Italy (n = 31) and Spain (n = 25) who elected for bariatric surgery. Data were integrated to evaluate the contribution of the gut microbiome to the molecular phenome (hepatic transcriptome, plasma and urine metabonome) of NAFLD independent of clinical confounders (age, BMI, cohort) using partial Spearman’s correlation. NAFLD activity score (NAS) was anti-correlated with microbial gene richness, and correlated with abundance of Proteobacteria. KEGG analyses of metagenomic data suggested increased microbial processing of dietary lipids and amino acids, as well as endotoxin-related processes related to Proteobacteria. Metabonomic profiles highlighted imbalances in choline metabolism, branched-chain amino acid (BCAA) metabolism and gut-derived microbial metabolites resulting from metabolism of amino acids. NAFLD-associated hepatic transcriptomes were associated with BCAA metabolism, endoplasmic reticulum/phagosome, and immune responses associated with non-specific microbial infections. Molecular phenomic signatures were stable and predictive regardless of sample size, and consistent with the microbiome making a significant contribution to the NAFLD phenome. There is disruption of the gut– liver axis in NAFLD, which can be seen in the gut microbiome, hepatic transcriptome and urinary and plasma metabonomes. Consistency of phenome signatures strongly supports a relationship between microbial amino acid metabolism and microbial gene richness, hepatic gene expression and biofluid metabonomes, and ultimately NAS.
Hoyles L, Fernandez-Real JM, Federici M, et al., 2017, Integrated systems biology to study non-alcoholic fatty liver disease in obese women, Tranlsational Bioinformatics
Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition and one of the most common causes of chronic liver disease, with increasing worldwide prevalence. Microbiome-associated lipopolysaccharides (LPS) are associated with NAFLD in rodent models, but their relevance in human liver disease is not understood. In addition, microbiome-driven degradation of dietary choline – and its subsequent removal from host-associated metabolic processes – is thought to contribute to development of NAFLD. The FLORINASH study set out to determine the contribution of the gut microbiome to the NAFLD-associated molecular phenome (transcriptome, metabonome) independent of clinical confounders.Morbidly obese women [body mass index (BMI) >35] from Italy (n = 31) and Spain (n = 25) who elected for bariatric surgery were recruited to the study. Clinical data (28 variables) were recorded. Faecal samples, liver biopsies, blood and urine samples were collected. Faecal metagenomes were analysed using an in-house metagenomics pipeline (SCaleble Automated Metagenomics Pipeline). NAFLD activity score (NAS; 0, 1, 2, 3) was determined by histological examination of liver biopsies. Differentially expressed genes in hepatic transcriptomes were identified, and analysed using several complementary tools. 1H-NMR data were generated for plasma and urinary metabonomes. Clinical, metagenomic, transcriptomic and metabonomic data were integrated using partial Spearman’s correlation, taking identified confounders (age, BMI and cohort) into account.NAS was anti-correlated with microbial gene richness, and correlated with abundance of Gram-negative Proteobacteria. KEGG analyses of metagenomic data suggested increased microbial processing of dietary lipids and amino acids, as well as LPS-related processes associated with Proteobacteria in NAFLD. Activation of immune responses associated with Gram-negative (LPS-associated) microbial infections was correlated with NAS in hepatic tr
Anwar MA, Adesina-Georgiadis KN, Spagou K, et al., 2017, A comprehensive characterisation of the metabolic profile of varicose veins; implications in elaborating plausible cellular pathways for disease pathogenesis, Scientific Reports, Vol: 7, ISSN: 2045-2322
Metabolic phenotypes reflect both the genetic and environmental factors which contribute to the development of varicose veins (VV). This study utilises analytical techniques to provide a comprehensive metabolic picture of VV disease, with the aim of identifying putative cellular pathways of disease pathogenesis. VV (n = 80) and non-VV (n = 35) aqueous and lipid metabolite extracts were analysed using 600 MHz 1H Nuclear Magnetic Resonance spectroscopy and Ultra-Performance Liquid Chromatography Mass Spectrometry. A subset of tissue samples (8 subjects and 8 controls) were analysed for microRNA expression and the data analysed with mirBase (www.mirbase.org). Using Multivariate statistical analysis, Ingenuity pathway analysis software, DIANALAB database and published literature, the association of significant metabolites with relevant cellular pathways were understood. Higher concentrations of glutamate, taurine, myo-inositol, creatine and inosine were present in aqueous extracts and phosphatidylcholine, phosphatidylethanolamine and sphingomyelin in lipid extracts in the VV group compared with non-VV group. Out of 7 differentially expressed miRNAs, spearman correlation testing highlighted correlation of hsa-miR-642a-3p, hsa-miR-4459 and hsa-miR-135a-3p expression with inosine in the vein tissue, while miR-216a-5p, conversely, was correlated with phosphatidylcholine and phosphatidylethanolamine. Pathway analysis revealed an association of phosphatidylcholine and sphingomyelin with inflammation and myo-inositol with cellular proliferation.
Ahmad MS, Damanhouri ZA, Kimhofer T, et al., 2017, A new gender-specific model for skin autofluorescence risk stratification (vol 5, pg 10198, 2015), Scientific Reports, Vol: 7, Pages: 1-1, ISSN: 2045-2322
Swann JR, Garcia-Perez I, Braniste V, et al., 2017, Application of 1H NMR spectroscopy to the metabolic phenotyping of rodent brain extracts: a metabonomic study of gut microbial influence on host brain metabolism, Journal of Pharmaceutical and Biomedical Analysis, Vol: 143, Pages: 141-146, ISSN: 1873-264X
H NMR Spectroscopy has been applied to determine the neurochemical profiles of brain extracts from the frontal cortex and hippocampal regions of germ free and normal mice and rats. The results revealed a number of differences between germ free (GF) and conventional (CV) rats or specific pathogen-free (SPF) mice with microbiome-associated metabolic variation found to be both species- and region-dependent. In the mouse, the GF frontal cortex contained lower amounts of creatine, N-acetyl-aspartate (NAA), glycerophosphocholine and lactate, but greater amounts of choline compared to that of specific pathogen free (SPF) mice. In the hippocampus, the GF mice had greater creatine, NAA, lactate and taurine content compared to those of the SPF animals, but lower relative quantities of succinate and an unidentified lipid-related component. The GF rat frontal cortex contained higher relative quantities of lactate, creatine and NAA compared to the CV animals whilst the GF hippocampus was characterized by higher taurine and phosphocholine concentrations and lower quantities of NAA, N-acetylaspartylglutamate and choline compared to the CV animals. Of note is that, in both rat and mouse brain extracts, concentrations of hippocampal taurine were found to be greater in the absence of an established microbiome. The results provide further evidence that brain biochemistry can be influenced by gut microbial status, specifically metabolites involved in energy metabolism demonstrating biochemical dialogue between the microbiome and brain.
Wolfer AM, Scott AJ, Rueb C, et al., 2017, Longitudinal analysis of serum oxylipin profile as a novel descriptor of the inflammatory response to surgery, JOURNAL OF TRANSLATIONAL MEDICINE, Vol: 15, ISSN: 1479-5876
Background:Oxylipins are potent lipid mediators demonstrated to initiate and regulate inflammation yet little is known regarding their involvement in the response to surgical trauma. As key modulators of the inflammatory response, oxylipins have the potential to provide novel insights into the physiological response to surgery and the pathophysiology of post-operative complications. We aimed to investigate the effects of major surgery on longitudinal oxylipin profile.Methods:Adults patients undergoing elective laparoscopic or open colorectal resections were included. Primary outcomes were serum oxylipin profile quantified by ultra high-performance liquid chromatography-mass spectrometry, serum white cell count and C-reactive protein concentration. Serum samples were taken at three time-points: pre-operative (day zero), early post-operative (day one) and late post-operative (day four/five).Results:Some 55 patients were included, of which 33 (60%) underwent surgery that was completed laparoscopically. Pre-operative oxylipin profiles were characterised by marked heterogeneity but surgery induced a common shift resulting in more homogeneity at the early post-operative time-point. By the late post-operative phase, oxylipin profiles were again highly variable. This evolution was driven by time-dependent changes in specific oxylipins. Notably, the levels of several oxylipins with anti-inflammatory properties (15-HETE and four regioisomers of DHET) were reduced at the early post-operative point before returning to baseline by the late post-operative period. In addition, levels of the pro-inflammatory 11-HETE rose in the early post-operative phase while levels of anti-thrombotic mediators (9-HODE and 13-HODE) fell; concentrations of all three oxylipins then remained fairly static from early to late post-operative phases. Compared to those undergoing laparoscopic surgery, patients undergoing open surgery had lower levels of some anti-inflammatory oxylipins (8,9-DHET and 17-HD
Hicks LC, Powles ST, Swann JR, et al., 2017, EFFECTS OF TIME ON URINARY METABOLIC SIGNATURES IN INFLAMMATORY BOWEL DISEASE, Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S611-S612, ISSN: 0016-5085
Qureshi MI, Vorkas P, Kaluarachchi M, et al., 2017, Biomarker research in thromboembolic stroke, Annual Meeting of the Society-of-Academic-and-Research-Surgery (SARS), Publisher: WILEY, Pages: 12-13, ISSN: 0007-1323
Antcliffe D, Jimenez B, Veselkov K, et al., 2017, Metabolic profiling in patients with pneumonia on intensive care, EBioMedicine, Vol: 18, Pages: 244-253, ISSN: 2352-3964
Clinical features and investigations lack predictive value when diagnosing pneumonia, especially when patients are ventilated and when patients develop ventilator associated pneumonia (VAP). New tools to aid diagnosis are important to improve outcomes. This pilot study examines the potential for metabolic profiling to aid the diagnosis in critical care.In this prospective observational study ventilated patients with brain injuries or pneumonia were recruited in the intensive care unit and serum samples were collected soon after the start of ventilation. Metabolic profiles were produced using 1D 1H NMR spectra. Metabolic data were compared using multivariate statistical techniques including Principal Component Analysis (PCA) and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA).We recruited 15 patients with pneumonia and 26 with brain injuries, seven of whom went on to develop VAP. Comparison of metabolic profiles using OPLS-DA differentiated those with pneumonia from those with brain injuries (R2Y = 0.91, Q2Y = 0.28, p = 0.02) and those with VAP from those without (R2Y = 0.94, Q2Y = 0.27, p = 0.05). Metabolites that differentiated patients with pneumonia included lipid species, amino acids and glycoproteins.Metabolic profiling shows promise to aid in the diagnosis of pneumonia in ventilated patients and may allow a more timely diagnosis and better use of antibiotics.
Shariff MIF, Kim JU, Ladep NG, et al., 2017, The plasma and serum metabotyping of hepatocellular carcinoma in a Nigerian and Egyptian cohort using proton nuclear magnetic resonance spectroscopy, Journal of Clinical and Experimental Hepatology, Vol: 7, Pages: 83-92, ISSN: 0973-6883
BACKGROUND/AIMS: Previous studies have observed disturbances in the (1)H nuclear magnetic resonance (NMR) blood spectral profiles in malignancy. No study has metabotyped serum or plasma of hepatocellular carcinoma (HCC) patients from two diverse populations. We aimed to delineate the HCC patient metabotype from Nigeria (mostly hepatitis B virus infected) and Egypt (mostly hepatitis C virus infected) to explore lipid and energy metabolite alterations that may be independent of disease aetiology, diet and environment. METHODS: Patients with HCC (53) and cirrhosis (26) and healthy volunteers (19) were recruited from Nigeria and Egypt. Participants provided serum or plasma samples, which were analysed using 600 MHz (1)H NMR spectroscopy with nuclear Overhauser enhancement spectroscopy pulse sequences. Median group spectra comparison and multivariate analysis were performed to identify regions of difference. RESULTS: Significant differences between HCC patients and healthy volunteers were detected in levels of low density lipoprotein (P = 0.002), very low density lipoprotein (P < 0.001) and lactate (P = 0.03). N-acetylglycoproteins levels in HCC patients were significantly different from both healthy controls and cirrhosis patients (P < 0.001 and 0.001). CONCLUSION: Metabotype differences were present, pointing to disturbed lipid metabolism and a switch from glycolysis to alternative energy metabolites with malignancy, which supports the Warburg hypothesis of tumour metabolism.
Qureshi MI, Greco M, Vorkas PA, et al., 2017, Application of metabolic profiling to abdominal aortic aneurysm research, Journal of Proteome Research, Vol: 16, Pages: 2325-2332, ISSN: 1535-3893
Abdominal aortic aneurysm (AAA) is a complex disease posing diagnostic and therapeutic challenges. Metabonomics may aid in the diagnosis of AAA, determination of individualized risk, discovery of therapeutic targets, and improve understanding of pathogenesis. A systematic review of the diversity and outcomes of existing AAA metabonomic research has been performed. Original research studies applying metabonomics to human aneurysmal disease are included. Seven relevant articles were identified: four studies were based on plasma/serum metabolite profiling, and three studies examined aneurysmal tissue. Aminomalonic acid, guanidinosuccinic acid, and glycerol emerge as potential plasma biomarkers of large aneurysm. Lipid profiling improves predictive models of aneurysm presence. Patterns of metabolite variation associated with AAA relate to carbohydrate and lipid metabolism. Perioperative perturbations in metabolites suggest differential systemic inflammatory responses to surgery, generating hypotheses for adjunctive perioperative therapy. Significant limitations include small study sizes, lack of correction for multiple testing false discovery rates, and single time-point sampling. Metabolic profiling carries the potential to identify biomarkers of AAA and elucidate pathways underlying aneurysmal disease. Statistically and methodologically robust studies are required for validation, addressing the hiatus in understanding mechanisms of aneurysm growth and developing effective treatment strategies.
Hoyles L, Fernández-Real JM, Federici M, et al., 2017, Integrated systems biology to study non-alcoholic fatty liver disease in obese women, Gut Microbiota for Health World Summit 2017
Objectives: To integrate metagenomic (faecal microbiome), transcriptomic, metabonomic and clinical data to evaluate the contribution of the gut microbiome to the molecular phenome (hepatic transcriptome, plasma and urine metabonome) of non-alcoholic fatty liver disease (NAFLD) independent of clinical confounders in morbidly obese women recruited to the FLORINASH study.Methods: Faecal, liver biopsy, blood and urine samples and data for 28 clinical variables were collected for 56 obese [body mass index (BMI) >35] women from Italy (n = 31) and Spain (n = 25) who elected for bariatric surgery. Confounder analyses of clinical data were done using linear modeling. Histological examination of liver biopsies was used to grade NAFLD (NAFLD activity score: 0, 1, 2, 3). Faecal metagenomes were generated and analysed using the Imperial Metagenomics Pipeline. Differentially expressed genes were identified in hepatic transcriptomes, and analysed using Enrichr, network analyses and Signaling Pathway Impact Analysis. 1H-NMR data were generated for plasma and urinary metabonomes. Clinical, metagenomic, transcriptomic and metabonomic data were integrated using partial Spearman’s correlation, taking confounders (age, body mass index and cohort) into account.Results: NAFLD activity score was anti-correlated with microbial gene richness, and correlated with abundance of Proteobacteria. KEGG analyses of metagenomic data suggested increased microbial processing of dietary lipids and amino acids, as well as endotoxin-related processes related to Proteobacteria. Metabonomic profiles highlighted imbalances in choline metabolism, branched-chain amino acid metabolism and gut-derived microbial metabolites resulting from metabolism of amino acids. NAFLD-associated hepatic transcriptomes were associated with branched-chain amino acid metabolism, endoplasmic reticulum/phagosome, and immune responses associated with microbial infections. Molecular phenomic signatures were stable and predic
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