المؤلفون: Geraldine F. Clough, Edward Gilbert-Kawai, Deborah Carey, Michael P.W. Grocott, Denny Z. H. Levett, Daniel Martin, Thomas W. Davies, Andrew J. Chipperfield, Michael G. Mythen, Marjola Thanaj, Kay Mitchell

المصدر: Scientific Reports, Vol 9, Iss 1, Pp 1-12 (2019)
Scientific Reports

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Acclimatization, lcsh:Medicine, 030204 cardiovascular system & hematology, Hypoxic exposure, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Hypoxia, lcsh:Science, Skin, Multidisciplinary, Chemistry, Altitude, Microcirculation, lcsh:R, Blood flow, Effects of high altitude on humans, Oxygen, Microvascular perfusion, Base camp, Tissue oxygenation, Microvascular Network, Cardiology, Female, Hypobaric hypoxia, lcsh:Q, Biomedical engineering, Perfusion, 030217 neurology & neurosurgery

الوصف: An increased and more effective microvascular perfusion is postulated to play a key role in the physiological adaptation of Sherpa highlanders to the hypobaric hypoxia encountered at high altitude. To investigate this, we used Lempel-Ziv complexity (LZC) analysis to explore the spatiotemporal dynamics of the variability of the skin microvascular blood flux (BF) signals measured at the forearm and finger, in 32 lowlanders (LL) and 46 Sherpa highlanders (SH) during the Xtreme Everest 2 expedition. Measurements were made at baseline (BL) (LL: London 35 m; SH: Kathmandu 1300 m) and at Everest base camp (LL and SH: EBC 5,300 m). We found that BF signal content increased with ascent to EBC in both SH and LL. At both altitudes, LZC of the BF signals was significantly higher in SH, and was related to local slow-wave flow-motion activity over multiple spatial and temporal scales. In SH, BF LZC was also positively associated with LZC of the simultaneously measured tissue oxygenation signals. These data provide robust mechanistic information of microvascular network functionality and flexibility during hypoxic exposure on ascent to high altitude. They demonstrate the importance of a sustained heterogeneity of network perfusion, associated with local vaso-control mechanisms, to effective tissue oxygenation during hypobaric hypoxia.

وصف الملف: text

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0d74552643761fb2b883866edd87669fTest
http://link.springer.com/article/10.1038/s41598-019-50774-0Test

المؤلفون: Mark Wright, Christopher D. Byrne, Janisha Patel, Nathalie M. Delzenne, Debbie E. Smith, Philip C. Calder, Helen Moyses, Eleonora Scorletti, Amal Almehmadi, Geraldine F. Clough, Elizabeth A. Miles, Laure B. Bindels, Paul R. Afolabi, Albandri Alshathry

المصدر: Contemporary Clinical Trials. 71:113-123

مصطلحات موضوعية: Liver Cirrhosis, Male, 0301 basic medicine, Magnetic Resonance Spectroscopy, Cirrhosis, Cultured Milk Products, medicine.medical_treatment, Placebo-controlled study, Oligosaccharides, Synbiotics, Type 2 diabetes, Gut flora, Gastroenterology, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, RNA, Ribosomal, 16S, Pharmacology (medical), biology, Fatty liver, General Medicine, Middle Aged, Treatment Outcome, Adipose Tissue, Liver, Cardiovascular Diseases, Disease Progression, Female, 030211 gastroenterology & hepatology, medicine.medical_specialty, digestive system, 03 medical and health sciences, Bifidobacterium animalis, Double-Blind Method, Internal medicine, medicine, Humans, Gene Silencing, business.industry, Prebiotic, medicine.disease, biology.organism_classification, Gastrointestinal Microbiome, Gastrointestinal Tract, 030104 developmental biology, Diabetes Mellitus, Type 2, Steatohepatitis, business, Genes, Microbial, Dysbiosis, Biomarkers

الوصف: Background Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of fat-related conditions ranging from simple fatty liver, to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. There is growing evidence that NAFLD is a multisystem disease, affecting several extra-hepatic organs and regulatory pathways. Furthermore, since the gut and liver are linked anatomically via the portal vein, disturbances of the gut microbiota (dysbiosis) can affect the liver. Objectives In patients with NAFLD, we are testing the effects of a synbiotic which is the combination of a prebiotic (fructooligosaccharides; 4 g/day) and a probiotic ( Bifidobacterium animalis subsp. lactis BB-12 at a minimum of 10 billion CFU/day) on a) liver fat percentage, b) NAFLD fibrosis algorithm scores, c) gut microbiota composition. Additionally, there will be several hypothesis-generating secondary outcomes to understand the metaorganismal pathways that influence the development and progression of NAFLD, type 2 diabetes, and cardiovascular risk. Design In a randomised double-blind placebo-controlled trial, 104 participants were randomised to 10–14 months intervention with either synbiotic (n = 55) or placebo (n = 49). Recruitment was completed in April 2017 and the last study visit will be completed by April 2018. Methods Change in gut microbiota composition will be assessed using 16S ribosomal RNA gene sequencing. Change in mean liver fat percentage will be quantified by magnetic resonance spectroscopy (MRS). In addition, change in liver fat severity will be measured using two NAFLD fibrosis algorithm scores. The INSYTE study was approved by the local ethics committee (REC: 12/SC/0614) and is registered at www.clinicaltrials.gov as NCT01680640 .

وصف الملف: text

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::796ba7f257f9d2764c3faa76e47a2f27Test
https://doi.org/10.1016/j.cct.2018.05.010Test

المؤلفون: Jefferson C. Frisbee, Geraldine F. Clough

المصدر: Experimental physiologyREFERENCES. 105(9)

مصطلحات موضوعية: medicine.medical_specialty, Nutrition and Dietetics, Physiology, business.industry, Microcirculation, Hemodynamics, General Medicine, Oxygenation, Blood flow, Oxygen, Physiology (medical), Internal medicine, Cardiology, Medicine, Humans, business

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2ea2a73c64efc63c4fcaf2e13a30b967Test
https://pubmed.ncbi.nlm.nih.gov/33448480Test

المؤلفون: Geraldine F. Clough, Christopher D. Byrne, Marjola Thanaj, Andrew J. Chipperfield, Eleonora Scorletti, Philip C. Calder

المصدر: Frontiers in Physiology
Frontiers in Physiology, Vol 11 (2020)

مصطلحات موضوعية: skin, medicine.medical_specialty, Physiology, microcirculation, Hemodynamics, 030204 cardiovascular system & hematology, non-linear complexity analysis, Gastroenterology, lcsh:Physiology, Microcirculation, 03 medical and health sciences, 0302 clinical medicine, NAFLD, Physiology (medical), Internal medicine, medicine, blood flow, Respiratory system, Reactive hyperemia, Original Research, liver fibrosis, sympathetic nervous system, lcsh:QP1-981, business.industry, Fatty liver, Type 2 Diabetes Mellitus, Neurovascular bundle, medicine.disease, Dilator, flow-motion, business, 030217 neurology & neurosurgery

الوصف: Background/Aims: Increasing evidence shows that non-alcoholic fatty liver disease (NAFLD) is associated with dysregulation of microvascular perfusion independently of established cardio-metabolic risk factors. We investigated whether hepatic manifestations of NAFLD such as liver fibrosis and liver fat are associated with microvascular hemodynamics through dysregulation of neurovascular control. Methods: Microvascular dilator (post-occlusive reactive hyperemia) and sympathetically mediated constrictor (deep inspiratory breath-hold) responses were measured at the forearm and finger, respectively, using laser Doppler fluximetry. Non-linear complexity-based analysis was used to assess the information content and variability of the resting blood flux (BF) signals, attributable to oscillatory flow-motion activity, and over multiple sampling frequencies. Results: Measurements were made in 189 adults (113 men) with NAFLD, with (n = 65) and without (n = 124) type 2 diabetes mellitus (T2DM), age = 50.9 ± 11.7 years (mean ± SD). Microvascular dilator and constrictor capacity were both negatively associated with age (r = −0.178, p = 0.014, and r = −0.201, p = 0.007, respectively) and enhanced liver fibrosis (ELF) score (r = −0.155, p = 0.038 and r = −0.418, p < 0.0001, respectively). There was no association with measures of liver fat, obesity or T2DM. Lempel-Ziv complexity (LZC) and sample entropy (SE) of the BF signal measured at the two skin sites were associated negatively with age (p < 0.01 and p < 0.001) and positively with ELF score (p < 0.05 and p < 0.0001). In individuals with an ELF score ≥7.8 the influence of both neurogenic and respiratory flow-motion activity on LZC was up-rated (p < 0.0001). Conclusion: Altered microvascular network functionality occurs in adults with NAFLD suggesting a mechanistic role for dysregulated neurovascular control in individuals at risk of severe liver fibrosis.

وصف الملف: text

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3a19d3b0210367bc3afeff98d61e592dTest
https://doi.org/10.3389/fphys.2020.00551Test

المؤلفون: Debbie E. Smith, Geraldine F. Clough, Antigoni Manousopoulou, Miltiadis Fotopoulos, Spiros D. Garbis, Christopher D. Byrne, Philip C. Calder, Jie Teng, Theodoros I. Roumeliotis, Eleonora Scorletti

مصطلحات موضوعية: Adult, Male, Proteomics, 0301 basic medicine, medicine.medical_specialty, Docosahexaenoic Acids, Quantitative proteomics, 030209 endocrinology & metabolism, Disease, Critical Care and Intensive Care Medicine, Placebo, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Immune system, Double-Blind Method, Non-alcoholic Fatty Liver Disease, Internal medicine, medicine, Humans, 030109 nutrition & dietetics, Nutrition and Dietetics, business.industry, Fatty liver, Blood Proteins, medicine.disease, Eicosapentaenoic Acid, Proteome, Female, lipids (amino acids, peptides, and proteins), Plasma proteomics, Metabolic syndrome, business

الوصف: Summary Background & aims Non-alcoholic fatty liver disease (NAFLD) is a liver condition characterised by liver fat accumulation and often considered to be the liver manifestation of metabolic syndrome. The aim of this study was to examine in patients with NAFLD the system-wide effects of treatment with docosahexaenoic acid + eicosapentaenoic acid (DHA + EPA) versus placebo on the plasma proteome. Methods Plasma from patients that participated in a 15–18 months randomised, double-blind placebo-controlled trial testing the effects of 4 g DHA + EPA daily was analysed using depletion-free quantitative proteomics. Results Bioinformatics interpretation of the proteomic analysis showed that DHA + EPA treatment affected pathways involving blood coagulation, immune/inflammatory response and cholesterol metabolism (p < 0.05). Two key proteins of cardiovascular risk, prothrombin and apolipoprotein B-100, were shown to decrease as a result of DHA + EPA supplementation [Prothrombin: Males DHA + EPA Mean iTRAQ log2ratio (SD) = −0.13 (0.20) p = 0.05, Females DHA + EPA Mean iTRAQ log2ratio (SD) = −0.48 (0.35) p = 0.03; Apo B-100: Males DHA + EPA Mean iTRAQ log2ratio (SD) = −0.24 (0.16) p = 0.01, Females DHA + EPA Mean iTRAQ log2ratio (SD) = −0.15 (0.05) p = 0.02]. Conclusions Plasma proteomics applied in a randomised, placebo-controlled trial showed that high dose DHA + EPA treatment in patients with NAFLD affects multiple pathways involved in chronic non-communicable diseases.

وصف الملف: text; image; application/pdf; application/msword; application/vnd.ms-excel

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1b9027b93ee9d77bc4496f77b855e62dTest
https://eprints.soton.ac.uk/424794Test/

المؤلفون: Joshua A. Welsh, Geraldine F. Clough, Eleonora Scorletti, Nicola A. Englyst, Christopher D. Byrne

المصدر: Journal of Leukocyte Biology. 104:631-639

مصطلحات موضوعية: Adult, Liver Cirrhosis, Male, 0301 basic medicine, CD31, medicine.medical_specialty, Immunology, Pilot Projects, Biology, Sensitivity and Specificity, Gastroenterology, Cohort Studies, Extracellular Vesicles, 03 medical and health sciences, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Fibrosis, Internal medicine, Nonalcoholic fatty liver disease, Leukocytes, medicine, Humans, Immunology and Allergy, Aged, medicine.diagnostic_test, Receiver operating characteristic, Fatty liver, Cell Biology, Extracellular vesicle, Middle Aged, Endoglin, medicine.disease, 030104 developmental biology, ROC Curve, Area Under Curve, Liver biopsy, Female, 030211 gastroenterology & hepatology, Algorithms, Biomarkers

الوصف: The enhanced liver fibrosis (LFS) score and the nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) are algorithmic-derived scores for diagnosing severe (F3/F4) liver fibrosis. In a pilot, substudy of the Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD with OMacor thErapy (WELCOME) trial, we tested whether measurements of plasma platelet-, endothelial-, and leukocyte-derived extracellular vesicles (EVs) counts are (a) associated with, and predict, F3/F4 fibrosis and (b) able to improve risk prediction of F3/F4 fibrosis in NAFLD, building upon LFS or NFS algorithms. Twenty-six individuals with NAFLD had liver fibrosis severity determined by Kleiner scoring after liver biopsy. Plasma samples stained with CD41a, CD42b, CD31, CD105, CD14, CD16, and CD284 antibodies were analyzed using flow cytometry to measure platelet-, endothelial-, and leukocyte-derived EVs counts. The independence of associations between EVs and F3/F4 fibrosis were tested using logistic regression. Receiver operator characteristic (ROC) curves were used to evaluate F3/F4 fibrosis prediction models. LFS was more strongly associated with F3/F4 fibrosis than NFS (χ2 = 15.403, P < 0.0001, and χ2 = 6.300, P = 0.012, respectively). The association between LFS and F3/F4 fibrosis was further improved by addition of CD14+ EVs (χ2 = 20.847, P = 0.016 vs. χ2 = 12.803 P = 0.015, respectively) or CD16+ EVs (χ2 = 22.205, P = 0.009 vs. χ2 = 17.559 P = 0.001, respectively), and the area under the ROC for LFS (AUC = 0.915, se = 0.055, P = 0.001) was increased by the addition of CD14+ or CD16+ EVs (AUC = 0.948, se = 0.042, and P < 0.001 and AUC = 0.967, se = 0.055, P < 0.001, respectively) as predictor variables. In this small preliminary study, CD14+ and CD16+ EV counts show potential to predict liver fibrosis severity with either marker improving the ability of the LFS to identify F3/F4 fibrosis in this small preliminary cohort study. In a small preliminary study, leukocyte extracellular vesicles show an inverse association with liver fibrosis in NAFLD, warranting their further investigation as biomarkers.

وصف الملف: text

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f1b04a9e44fb4653c8e190dc37e0fe94Test
https://doi.org/10.1002/jlb.5a1217-501rTest

المؤلفون: Michael J. Griffin, Eleonora Scorletti, Philip C. Calder, Geraldine F. Clough, Christopher D. Byrne, Keith McCormick, Lokpal Bhatia

المصدر: ResearcherID

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Docosahexaenoic Acids, genetic structures, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Type 2 diabetes, Cardiovascular System, Gastroenterology, Body fat percentage, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Double-Blind Method, Non-alcoholic Fatty Liver Disease, Internal medicine, Internal Medicine, medicine, Humans, chemistry.chemical_classification, business.industry, Microcirculation, Fatty liver, Temperature, Fatty acid, Middle Aged, medicine.disease, Eicosapentaenoic acid, Surgery, Fatty Liver, Drug Combinations, medicine.anatomical_structure, Diabetes Mellitus, Type 2, Eicosapentaenoic Acid, chemistry, Docosahexaenoic acid, Female, Insulin Resistance, business, 030217 neurology & neurosurgery, Sensory nerve

الوصف: The effect of n-3 fatty acid treatment on temperature perception as a sensory nerve function modality is uncertain. In patients with non-alcoholic fatty liver disease (NAFLD) both with and without type 2 diabetes, we: (1) tested whether 15-18 months' treatment with 4 g/day of docosahexaenoic plus eicosapentaenoic acid (DHA+EPA) improved hot (HPT) and cold (CPT) temperature perception thresholds and (2) explored factors associated with HPT and CPT, in a randomised, double-blind, placebo-controlled trial.The effect of treatment (n = 44) on HPT, CPT and temperature perception index (TPI: difference between HPT and CPT) was measured at the big toe in 90 individuals without neuropathy (type 2 diabetes; n = 30). Participants were randomised 1:1, using sequential numbering, by personnel independent from the trial team. All participants and all members of the research team were blinded to group assignment. Data were collected in the Southampton National Institute for Health Research Biomedical Research Centre. Treatment effects and the independence of associations were testing by regression modelling.Mean ± SD age was 50.9 ± 10.6 years. In men (n = 53) and women (n = 37), HPTs (°C) were 46.1 ± 5.1 and 43.1 ± 6.4 (p = 0.02), CPTs (°C) were 22.7 ± 3.4 and 24.5 ± 3.6 (p = 0.07) and TPIs (°C) were 23.4 ± 7.4 and 18.7 ± 9.5 (p = 0.008), respectively. In univariate analyses, total body fat percentage (measured by dual-energy x-ray absorptiometry [DXA]) was associated with HPT (r = -0.36 p = 0.001), CPT (r = 0.35 p = 0.001) and TPI (r = 0.39 p = 0.0001). In multivariable-adjusted regression models, adjusting for age, sex and other potential confounders, only body fat percentage was independently associated with HPT, CPT or TPI (p = 0.006, p = 0.006 and p = 0.002, respectively). DHA+EPA treatment did not modify HPT, CPT or TPI (p = 0.93, p = 0.44 and p = 0.67, respectively). There were no important adverse effects or side effects reported.Higher body fat percentage is associated with enhanced temperature perception. There was no benefit of treatment with high-dose n-3 fatty acids on the thresholds to detect hot or cold stimuli.ClinicalTrials.gov NCT00760513 FUNDING: This work was supported by the National Institute for Health Research through the NIHR Southampton Biomedical Research Unit grant and by a Diabetes UK allied health research training fellowship awarded to KMcC (Diabetes UK. BDA 09/0003937).

وصف الملف: text

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4d04337c6eb118bec9d0fcdfe940fc01Test
https://doi.org/10.1007/s00125-016-3966-8Test

المؤلفون: Lokpal Bhatia, Geraldine F. Clough, Eleonora Scorletti, Christopher D. Byrne, Philip C. Calder, Nick Curzen

المصدر: Atherosclerosis. 246:13-20

مصطلحات موضوعية: Adult, Carotid Artery Diseases, Male, medicine.medical_specialty, Pathology, Magnetic Resonance Spectroscopy, Time Factors, Docosahexaenoic Acids, 030204 cardiovascular system & hematology, Placebo, Carotid Intima-Media Thickness, Severity of Illness Index, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Non-alcoholic Fatty Liver Disease, Predictive Value of Tests, Internal medicine, medicine, Humans, chemistry.chemical_classification, Ultrasonography, Doppler, Duplex, business.industry, Surrogate endpoint, Fatty liver, Middle Aged, medicine.disease, Eicosapentaenoic acid, Drug Combinations, Carotid Arteries, Treatment Outcome, Eicosapentaenoic Acid, chemistry, Intima-media thickness, Docosahexaenoic acid, Cohort, Disease Progression, Female, 030211 gastroenterology & hepatology, Cardiology and Cardiovascular Medicine, business, Biomarkers, Polyunsaturated fatty acid

الوصف: Background and aims: n-3 polyunsaturated fatty acid (PUFA) treatment may decrease liver fat in non-alcoholic fatty liver disease (NAFLD), but uncertainty exists whether this treatment also decreases cardiovascular disease (CVD) risk in NAFLD. We tested whether 15–18 months n-3 PUFA [docosahexaenoic acid (DHA) and eicosapentaenoic acid] (Omacor/Lovaza, 4 g/day) vs placebo decreased carotid intima-media thickness (CIMT) progression, a surrogate marker of CVD risk. We also evaluated if improvement in markers of NAFLD severity was associated with decreased CIMT progression over time.Methods: In a pre-specified sub-study of the WELCOME (Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD with OMacor thErapy) trial (NCT00760513), CIMT was measured using B-mode ultrasound while NAFLD severity was assessed by measuring liver fat percentage (magnetic resonance spectroscopy) and hepatic necro-inflammation (serum cytokeratin-18 (CK-18) concentration), at baseline and end of study.Results: 92 patients (age 51.5 ± 10.7 years, 57.6% men) completed the study. In the treatment group (n = 45), CIMT progressed by 0.012 mm (IQR 0.005–0.020 mm) compared to 0.015 mm (IQR 0.007–0.025 mm) in the placebo group (n = 47) (p = 0.17). Reduced CIMT progression in the entire cohort was independently associated with decreased liver fat (standardized ?-coefficient 0.32, p = 0.005), reduced CK-18 levels (standardized ?-coefficient 0.22, p = 0.04) and antihypertensive usage (standardized ?-coefficient ?0.31, p = 0.009) in multivariable regression analysis after adjusting for all potential confounders. Decreased weight (standardized ?-coefficient 0.30, p < 0.001) and increased DHA tissue enrichment during the 18-month study (standardized ?-coefficient ?0.19, p = 0.027) were both independently associated with decreased liver fat, but not with CK-18.Conclusion: Improvement in two markers of NAFLD severity is independently associated with reduced CIMT progression.

وصف الملف: text

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8edd805e841ec64a6783c73bbf601387Test
https://doi.org/10.1016/j.atherosclerosis.2015.12.028Test

المؤلفون: Annette L. West, Christopher D. Byrne, Geraldine F. Clough, Keith McCormick, Eleonora Scorletti, Graham C. Burdge, Samuel P. Hoile, Philip C. Calder, Karen A. Lillycrop, Lokpal Bhatia

المصدر: Journal of Hepatology. 63:1476-1483

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Docosahexaenoic Acids, Genotype, Biology, Polymorphism, Single Nucleotide, chemistry.chemical_compound, Liver disease, Double-Blind Method, Non-alcoholic Fatty Liver Disease, Internal medicine, medicine, Humans, Omega 3 fatty acid, Triglycerides, Aged, chemistry.chemical_classification, Hepatology, Triglyceride, Fatty liver, Genetic Variation, Membrane Proteins, Fatty acid, Lipase, Middle Aged, Lipid Metabolism, medicine.disease, Eicosapentaenoic acid, Drug Combinations, Endocrinology, Eicosapentaenoic Acid, Liver, chemistry, Docosahexaenoic acid, Dietary Supplements, Female, TM6SF2

الوصف: Background & Aims Genetic variation in both patatin-like phospholipase domain-containing protein-3 (PNPLA3) (I148M) and the transmembrane 6 superfamily member 2 protein (TM6SF2) (E167K) influences severity of liver disease, and serum triglyceride concentrations in non-alcoholic fatty liver disease (NAFLD), but whether either genotype influences the responses to treatments is uncertain. Methods One hundred three patients with NAFLD were randomised to omega-3 fatty acids (DHA+EPA) or placebo for 15–18 months in a double blind placebo controlled trial. Erythrocyte enrichment with DHA and EPA was measured by gas chromatography. PNPLA3 and TM6SF2 genotypes were measured by PCR technologies. Multivariable linear regression and analysis of covariance were undertaken to test the effect of genotypes on omega-3 fatty acid enrichment, end of study liver fat percentage and serum triglyceride concentrations. All models were adjusted for baseline measurements of each respective outcome. Results Fifty-five men and 40 women (Genotypes PNPLA3 I148M, 148I/I = 41, 148I/M = 43, 148M/M = 11; TM6SF2 E167K 167E/E = 78, 167E/K+167K/K = 17 participants) (mean ± SD age, 51 ± 11 years) completed the trial. Adjusting for baseline measurement, measured covariates and confounders, PNPLA3 148M/M variant was independently associated with percentage of DHA enrichment (B coefficient −1.02 (95% CI −1.97, −0.07), p = 0.036) but not percentage of EPA enrichment (B coefficient −0.31 (95% CI −1.38, 0.75), p = 0.56). This genotype was also independently associated with end of study liver fat percentage (B coefficient 9.5 (95% CI 2.53, 16.39), p = 0.008), but not end of study triglyceride concentration (B coefficient −0.11 (95% CI −0.64, 0.42), p = 0.68). Conclusions PNPLA3 148M/M variant influences the changes in liver fat and DHA tissue enrichment during the trial but not the change in serum triglyceride concentration.

وصف الملف: text

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::49f039803d66326876efa3191a579e1fTest
https://doi.org/10.1016/j.jhep.2015.07.036Test

المؤلفون: Eleonora Scorletti, Albandri Alshathry, Mark Wright, Jaswinder K. Sethi, Caroline E. Childs, Stefania Del Fabbro, Charles Peebles, Debbie E. Smith, Amal Almehmadi, Angela Darekar, Helen Moyses, Geraldine F. Clough, Paul R. Afolabi, Josh Bilson, Richard Aspinall, Janisha Patel, Philip C. Calder, Giovanni Targher, Laure B. Bindels, Elizabeth A. Miles, Joanna Dowman, Christopher D. Byrne, Nathalie M. Delzenne, Andrew Fowell, Valerio Nobili, David J. Breen

المساهمون: UCL - SSS/LDRI - Louvain Drug Research Institute

المصدر: Gastroenterology, Vol. 158, no. 6, p. 1597-1610.e7 (2020)
Gastroenterology

مصطلحات موضوعية: Liver Cirrhosis, Male, 0301 basic medicine, Magnetic Resonance Spectroscopy, Synbiotics, Biopsy, medicine.medical_treatment, Oligosaccharides, Type 2 diabetes, Gastroenterology, Feces, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Weight loss, Cardiovascular Disease, Nonalcoholic fatty liver disease, Middle Aged, Cardiovascular disease, Lipids, Type 2 Diabetes, Liver, Elasticity Imaging Techniques, Female, 030211 gastroenterology & hepatology, medicine.symptom, Adult, medicine.medical_specialty, Placebo, Proof of Concept Study, Article, INSYTE Study, Nutrition, 03 medical and health sciences, Bifidobacterium animalis, Double-Blind Method, Internal medicine, Diabetes mellitus, medicine, Humans, Hepatology, business.industry, Prebiotic, medicine.disease, United Kingdom, Gastrointestinal Microbiome, 030104 developmental biology, INSYTE study, Dysbiosis, Transient elastography, business, Biomarkers

الوصف: BACKGROUND & AIMS: Dysbiosis of the intestinal microbiota has been associated with nonalcoholic fatty liver disease (NAFLD). We investigated whether administration of a synbiotic combination of probiotic and prebiotic agents affected liver fat content, biomarkers of liver fibrosis, and the composition of the fecal microbiome in patients with NAFLD.METHODS: We performed a double-blind phase 2 trial of 104 patients with NAFLD in the United Kingdom. Participants (mean age, 50.8 ± 12.6 years; 65% men; 37% with diabetes) were randomly assigned to groups given the synbiotic agents (fructo-oligosaccharides, 4 g twice per day, plus Bifidobacterium animalis subspecies lactis BB-12; n = 55) or placebo (n = 49) for 10-14 months. Liver fat content was measured at the start and end of the study by magnetic resonance spectroscopy, and liver fibrosis was determined from a validated biomarker scoring system and vibration-controlled transient elastography. Fecal samples were collected at the start and end of the study, the fecal microbiome were analyzed by 16S ribosomal DNA sequencing.RESULTS: Mean baseline and end-of-study magnetic resonance spectroscopy liver fat percentage values were 32.3% ± 24.8% and 28.5% ± 20.1% in the synbiotic group and 31.3% ± 22% and 25.2% ± 17.2% in the placebo group. In the unadjusted intention-to-treat analysis, we found no significant difference in liver fat reduction between groups (β = 2.8; 95% confidence interval, -2.2 to 7.8; P = .30). In a fully adjusted regression model (adjusted for baseline measurement of the outcome plus age, sex, weight difference, and baseline weight), only weight loss was associated with a significant decrease in liver fat (β = 2; 95% confidence interval, 1.5-2.6; P = .03). Fecal samples from patients who received the synbiotic had higher proportions of Bifidobacterium and Faecalibacterium species, and reductions in Oscillibacter and Alistipes species, compared with baseline; these changes were not observed in the placebo group. Changes in the composition of fecal microbiota were not associated with liver fat or markers of fibrosis.CONCLUSIONS: In a randomized trial of patients with NAFLD, 1 year of administration of a synbiotic combination (probiotic and prebiotic) altered the fecal microbiome but did not reduce liver fat content or markers of liver fibrosis. (ClinicalTrials.gov, Number: NCT01680640).

وصف الملف: text; image

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3857e54022068c72805f39fe3e794afdTest
https://doi.org/10.1053/j.gastro.2020.01.031Test