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1.
Herbert SB Baraf Michael A Becker Sergio R Gutierrez-Urena Edward L Treadwell Janitzia Vazquez-Mellado Claudia D Rehrig Faith D Ottery John S Sundy Robert A Yood 《Arthritis research & therapy》2013,15(5):R137
Introduction
Two replicate randomized, placebo-controlled six-month trials (RCTs) and an open-label treatment extension (OLE) comprised the pegloticase development program in patients with gout refractory to conventional therapy. In the RCTs, approximately 40% of patients treated with the approved dose saw complete response (CR) of at least one tophus. Here we describe the temporal course of tophus resolution, total tophus burden in patients with multiple tophi, tophus size at baseline, and the relationship between tophus response and urate-lowering efficacy.Methods
Baseline subcutaneous tophi were analyzed quantitatively using computer-assisted digital images in patients receiving pegloticase (8 mg biweekly or monthly) or placebo in the RCTs, and pegloticase in the OLE. Tophus response, a secondary endpoint in the trials, was evaluated two ways. Overall tophus CR was the proportion of patients achieving a best response of CR (without any new/enlarging tophi) and target tophus complete response (TT-CR) was the proportion of all tophi with CR.Results
Among 212 patients randomized in the RCTs, 155 (73%) had ≥1 tophus and 547 visible tophi were recorded at baseline. Overall tophus CR was recorded in 45% of patients in the biweekly group (P = 0.002 versus placebo), 26% in the monthly group, and 8% in the placebo group after six months of RCT therapy. TT-CR rates at six months were 28%, 19%, and 2% of tophi, respectively. Patients meeting the primary endpoint of sustained urate-lowering response to therapy (responders) were more likely than nonresponders to have an overall tophus CR at six months (54% vs 20%, respectively and 8% with placebo).Both overall tophus CR and TT-CRs increased with treatment duration in the OLE, reaching 70% (39/56) of patients and 55% (132/238) of target tophi after one year of treatment in patients receiving pegloticase during both the RCTs and OLE. At that time point, more tophi had resolved in responders (102/145 or 70% of tophi) than nonresponders (30/93; 32%).Conclusions
Pegloticase reduced tophus burden in patients with refractory tophaceous gout, especially those achieving sustained urate-lowering. Complete resolution of tophi occurred in some patients by 13 weeks and in others with longer-term therapy.Trial registrations
, NCT00325195 NCT01356498相似文献2.
Background
As the World Health Organization grading system for gastroenteropancreatic-neuroendocrine tumors (GEP-NETs) may not always correlate with tumor progression, it is imperative that other independent predictors of tumor progression be established. To identify such predictors, we conducted a retrospective histopathological study of hindgut NETs, obtained from endoscopic procedures, and used statistical analyses to evaluate predictive factors.Methods
We first obtained clinicopathological data of cases of hindgut NETs. Tissue sections from tumor samples were prepared and subjected to pathological examination. In particular, we calculated the microvessel density (MVD) and lymphatic microvessel density (LMVD) values, and performed appropriate statistical analyses.Results
A total of 42 cases of hindgut NETs were selected for the study, 41 from the rectum and 1 from the sigmoid colon. Based on the Ki-67 labeling index, 34 cases were classified as NET G1 tumors and 8 as NET G2 tumors. MVD values ranged from 1.4/mm2 to 73.9/mm2 and LMVD values from 0/mm2 to 22.9/mm2. MVD and LMVD were identified as risk factors for venous and lymphatic invasion of hindgut NETs. Moreover, MVD positively correlated with the maximum diameter of the tumor.Conclusions
Tumor progression of NETs may cause angiogenesis and lymphangiogenesis, via an unknown mechanism, as well as lymphovascular invasion. Angiogenesis likely plays an important role in occurrence and progression in the initial phase of hindgut NETs.3.
Background
The reconstruction of ancestral genomes must deal with the problem of resolution, necessarily involving a trade-off between trying to identify genomic details and being overwhelmed by noise at higher resolutions.Results
We use the median reconstruction at the synteny block level, of the ancestral genome of the order Gentianales, based on coffee, Rhazya stricta and grape, to exemplify the effects of resolution (granularity) on comparative genomic analyses.Conclusions
We show how decreased resolution blurs the differences between evolving genomes, with respect to rate, mutational process and other characteristics.4.
D. Jacob C. Deborde M. Lefebvre M. Maucourt A. Moing 《Metabolomics : Official journal of the Metabolomic Society》2017,13(4):36
Introduction
Concerning NMR-based metabolomics, 1D spectra processing often requires an expert eye for disentangling the intertwined peaks.Objectives
The objective of NMRProcFlow is to assist the expert in this task in the best way without requirement of programming skills.Methods
NMRProcFlow was developed to be a graphical and interactive 1D NMR (1H & 13C) spectra processing tool.Results
NMRProcFlow (http://nmrprocflow.org), dedicated to metabolic fingerprinting and targeted metabolomics, covers all spectra processing steps including baseline correction, chemical shift calibration and alignment.Conclusion
Biologists and NMR spectroscopists can easily interact and develop synergies by visualizing the NMR spectra along with their corresponding experimental-factor levels, thus setting a bridge between experimental design and subsequent statistical analyses.5.
Alexis Catala Rachel Culp-Hill Travis Nemkov Angelo D’Alessandro 《Metabolomics : Official journal of the Metabolomic Society》2018,14(7):100
Introduction
Mass spectrometry and computational biology have advanced significantly in the past ten years, bringing the field of metabolomics a step closer to personalized medicine applications. Despite these analytical advancements, collection of blood samples for routine clinical analysis is still performed through traditional blood draws.Objective
TAP capillary blood collection has been recently introduced for the rapid, painless draw of small volumes of blood (~?100 μL), though little is known about the comparability of metabolic phenotypes of blood drawn via traditional venipuncture and TAP devices.Methods
UHPLC-MS-targeted metabolomics analyses were performed on blood drawn traditionally or through TAP devices from 5 healthy volunteers. Absolute quantitation of 45 clinically-relevant metabolites was calculated against stable heavy isotope-labeled internal standards.Results
Ranges for 39 out of 45 quantified metabolites overlapped between drawing methods. Pyruvate and succinate were over threefold higher in the TAP samples than in traditional blood draws. No significant changes were observed for other carboxylates, glucose or lactate. TAP samples were characterized by increases in reduced glutathione and decreases in urate and cystine, markers of oxidation of purines and cysteine—overall suggesting decreased oxidation during draws. The absolute levels of bile acids and acyl-carnitines, as well as almost all amino acids, perfectly correlated among groups (Spearman r?≥?0.95).Conclusion
Though further more extensive studies will be mandatory, this pilot suggests that TAP-derived blood may be a logistically-friendly source of blood for large scale metabolomics studies—especially those addressing amino acids, glycemia and lactatemia as well as bile acids, acyl-carnitine levels.6.
Aims
The mechanisms underlying magnesium (Mg) uptake by plant roots remain to be fully elucidated. In particular, there is little information about the effects of Mg deficiency on Mg uptake activity. A Mg uptake kinetic study is essential for better understanding the Mg uptake system.Methods
We performed a Mg uptake tracer experiment in rice plants using 28?Mg.Results
Mg uptake was mediated by high- and low-affinity transport systems. The K m value of the high-affinity transport system was approximately 70 μM under Mg-deficient conditions. The Mg uptake activity was promoted by Mg deficiency, which in turn fell to the basal level after 5- min of Mg resupply. The induced uptake rate was inhibited by ionophore treatment, suggesting that an energy-dependent uptake system is enhanced by Mg deficiency.Conclusions
The Mg uptake changes rapidly with Mg conditions in rice, as revealed by a 28?Mg tracer experiment. This technique is expected to be applicable for Mg uptake analyses, particularly in mutants or other lines.7.
Objectives
Establish a method to indirectly measure evaporation in microwell-based cell culture systems and show that the proposed method allows compensating for liquid losses in fed-batch processes.Results
A correlation between evaporation and the concentration of Na+ was found (R2?=?0.95) when using the 24-well-based miniature bioreactor system (micro-Matrix) for a batch culture with GS-CHO. Based on these results, a method was developed to counteract evaporation with periodic water additions based on measurements of the Na+ concentration. Implementation of this method resulted in a reduction of the relative liquid loss after 15 days of a fed-batch cultivation from 36.7?±?6.7% without volume corrections to 6.9?±?6.5% with volume corrections.Conclusion
A procedure was established to indirectly measure evaporation through a correlation with the level of Na+ ions in solution and deriving a simple formula to account for liquid losses.8.
Daniel Morvan Aicha Demidem 《Metabolomics : Official journal of the Metabolomic Society》2018,14(5):55
Introduction
Elucidating molecular alterations due to mitochondrial Complex I (CI) mutations may help to understand CI deficiency (CID), not only in mitochondriopathies but also as it is caused by drugs or associated to many diseases.Objectives
CID metabolic expression was investigated in Leber’s hereditary optic neuropathy (LHON) caused by an inherited mutation of CI.Methods
NMR-based metabolomics analysis was performed in intact skin fibroblasts from LHON patients. It used several datasets: one-dimensional 1H-NMR spectra, two-dimensional 1H-NMR spectra and quantified metabolites. Spectra were analysed using orthogonal partial least squares-discriminant analysis (OPLS-DA), and quantified metabolites using univariate statistics. The response to idebenone (IDE) and resveratrol (RSV), two agents improving CI activity and mitochondrial functions was evaluated.Results
LHON fibroblasts had decreased CI activity (??43%, p?<?0.01). Metabolomics revealed prominent alterations in LHON including the increase of fatty acids (FA), polyunsaturated FA and phosphatidylcholine with a variable importance in the prediction (VIP)?>?1 in OPLS-DA, p?<?0.01 in univariate statistics, and the decrease of amino acids (AA), predominantly glycine, glutamate, glutamine (VIP?>?1) and alanine (VIP?>?1, p?<?0.05). In LHON, treatment with IDE and RSV increased CI activity (+?40 and +?44%, p?<?0.05). IDE decreased FA, polyunsaturated FA and phosphatidylcholine (p?<?0.05), but did not modified AA levels. RSV decreased polyunsaturated FA, and increased several AA (VIP?>?1 and/or p?<?0.05).Conclusion
LHON fibroblasts display lipid and amino acid metabolism alterations that are reversed by mitochondria-targeted treatments, and can be related to adaptive changes. Findings bring insights into molecular changes induced by CI mutation and, beyond, CID of other origins.9.
Olaia Liñero Jean-Yves Cornu Frederic Candaudap Oleg S. Pokrovsky Sylvie Bussière Cécile Coriou Théophile Humann-Guilleminot Thierry Robert Stéphane Thunot Alberto de Diego Christophe Nguyen 《Plant and Soil》2016,408(1-2):163-181
Aims
This work concentrated on understanding the allocation of Cd recently taken up between the organs of sunflower at early and middle reproductive growth stages. The roles of transpiration and allometry were investigated.Methods
Sunflowers were grown hydroponically in greenhouse, being exposed to low concentrations of Cd (pCd2+ = 11.03). At flower bud and grain filling stages, plants were exposed for three days to 111Cd and at the same time, subjected or not to fans to increase the transpiration. The partitioning of 111Cd between plant organs measured by high resolution ICP-MS was then modelled.Results
Although the use of fans increased the plant water uptake and transpiration by about 20%, there were no significant effects on the partitioning of recent Cd. Most of the recent Cd was recovered in roots (60%) and only 2.8% were found in seeds (0.8% for the husk and 2.0% for the almonds). The sequestration of recent Cd in a plant organ was successfully explained by its biomass and except for leaves, by the biomass of other organs acting as competitive sinks.Conclusions
This work proposes a modelling approach for the partitioning of the labelled Cd between plant organs in sunflower.10.
Takeo Moriya Yoshinori Satomi Hiroyuki Kobayashi 《Metabolomics : Official journal of the Metabolomic Society》2016,12(12):179
Introduction
Human plasma metabolomics offer powerful tools for understanding disease mechanisms and identifying clinical biomarkers for diagnosis, efficacy prediction and patient stratification. Although storage conditions can affect the reliability of data from metabolites, strict control of these conditions remains challenging, particularly when clinical samples are included from multiple centers. Therefore, it is necessary to consider stability profiles of each analyte.Objectives
The purpose of this study was to extract unstable metabolites from vast metabolome data and identify factors that cause instability.Method
Plasma samples were obtained from five healthy volunteers, were stored under ten different conditions of time and temperature and were quantified using leading-edge metabolomics. Instability was evaluated by comparing quantitation values under each storage condition with those obtained after ?80 °C storage.Result
Stability profiling of the 992 metabolites showed time- and temperature-dependent increases in numbers of significantly changed metabolites. This large volume of data enabled comparisons of unstable metabolites with their related molecules and allowed identification of causative factors, including compound-specific enzymatic activity in plasma and chemical reactivity. Furthermore, these analyses indicated extreme instability of 1-docosahexaenoylglycerol, 1-arachidonoylglycerophosphate, cystine, cysteine and N6-methyladenosine.Conclusion
A large volume of data regarding storage stability was obtained. These data are a contribution to the discovery of biomarker candidates without misselection based on unreliable values and to the establishment of suitable handling procedures for targeted biomarker quantification.11.
Clara Pérez-Rambla Leonor Puchades-Carrasco María García-Flores José Rubio-Briones José Antonio López-Guerrero Antonio Pineda-Lucena 《Metabolomics : Official journal of the Metabolomic Society》2017,13(5):52
Introduction
Prostate cancer (PCa) is one of the most common malignancies in men worldwide. Serum prostate specific antigen (PSA) level has been extensively used as a biomarker to detect PCa. However, PSA is not cancer-specific and various non-malignant conditions, including benign prostatic hyperplasia (BPH), can cause a rise in PSA blood levels, thus leading to many false positive results.Objectives
In this study, we evaluated the potential of urinary metabolomic profiling for discriminating PCa from BPH.Methods
Urine samples from 64 PCa patients and 51 individuals diagnosed with BPH were analysed using 1H nuclear magnetic resonance (1H-NMR). Comparative analysis of urinary metabolomic profiles was carried out using multivariate and univariate statistical approaches.Results
The urine metabolomic profile of PCa patients is characterised by increased concentrations of branched-chain amino acids (BCAA), glutamate and pseudouridine, and decreased concentrations of glycine, dimethylglycine, fumarate and 4-imidazole-acetate compared with individuals diagnosed with BPH.Conclusion
PCa patients have a specific urinary metabolomic profile. The results of our study underscore the clinical potential of metabolomic profiling to uncover metabolic changes that could be useful to discriminate PCa from BPH in a clinical context.12.
N. Cesbron A.-L. Royer Y. Guitton A. Sydor B. Le Bizec G. Dervilly-Pinel 《Metabolomics : Official journal of the Metabolomic Society》2017,13(8):99
Introduction
Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.Objectives
In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.Methods
The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.Results
A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.Conclusion
The workflow generated repeatable and informative fingerprints for robust metabolome characterization.13.
D.H.F. Gommans J. Bakker G.E. Cramer F.W.A. Verheugt M.A. Brouwer M.J.M. Kofflard 《Netherlands heart journal》2016,24(5):326-331
Purpose
The use of cardiac magnetic resonance (CMR) analysis has increased in patients with hypertrophic cardiomyopathy (HCM). Quantification of left ventricular (LV) measures will be affected by the inclusion or exclusion of the papillary muscles as part of the LV mass, but the magnitude of effect and potential consequences are unknown.Methods
We performed Cine-CMR in (1) clinical HCM patients (n?=?55) and (2) subclinical HCM mutation carriers without hypertrophy (n?=?14). Absolute and relative differences in LV ejection fraction (EF) and mass were assessed between algorithms with and without inclusion of the papillary muscles.Results
Papillary muscle mass in group 1 was 6.6?±?2.5 g/m2 and inclusion of the papillary muscles resulted in significant relative increases in LVEF of 4.5?±?1.8?% and in LV mass of 8.7?±?2.6?%. For group 2 these figures were 4.0?±?0.9 g/m2, 3.8?±?1.0?% and 9.5?±?1.8?%, respectively. With a coefficient of variation of 4?%, this 9?% difference in LV mass during CMR follow-up will be considered a change, while in fact the exact same mass may have been assessed according to two different algorithms.Conclusions
In clinical HCM patients, CMR quantification of important LV measures is significantly affected by inclusion or exclusion of the papillary muscles. In relative terms, the difference was similar in subjects without hypertrophy. This underscores a general need for a uniform approach in CMR image analysis.14.
Mélanie Abonnenc David Crettaz Laure Marvin Baptiste Grund Giona Sonego Manon Bardyn Jean-Daniel Tissot Michel Prudent Bertrand Rochat Niels Lion 《Metabolomics : Official journal of the Metabolomic Society》2016,12(12):188
Introduction
Research in transfusion medicine is motivated by the desire to deliver the most-compatible and most-efficient blood product to the patient. It is now well accepted that ex vivo platelet concentrates (PCs) experience biochemical alterations and a functional decline known as storage lesions. Photochemical treatments have been introduced to secure PCs against pathogens but are reported to accelerate these lesions.Objectives
The objective of this study was to investigate metabolic changes in stored PCs treated for pathogen inactivation with the INTERCEPT Blood system (Cerus, Concord, USA).Methods
PCs either untreated (uPCs) or INTERCEPT-treated (iPCs) were sampled along the 7-day storage period. First, metabolites were extracted and analyzed using ultra-high pressure liquid chromatography—high resolution mass spectrometry followed by statistical analysis. Secondly, we investigated the role of urate, a major plasma antioxidant, in the platelet function using flow cytometry-based assays.Results
We observed oxidative damages in stored iPCs compared to uPCs, in particular alteration of the purine and the glutathione metabolism. We showed diminution of antioxidant defenses following INTERCEPT treatment such as the conversion of urate to allantoin, only possible in humans under the action of reactive oxygen species (ROS). Functional assays on platelets in absence or in an excess of urate suggest a protective role of urate in PCs.Conclusion
Our results indicate oxidative damages occurring at the metabolic level in stored iPCs. Understanding better the role of antioxidants such as urate in ex vivo PCs would definitively provide new insights to ameliorate the storage conditions and preserve the functionality of platelets.15.
E. Dervishi G. Zhang D. Hailemariam R. Mandal D. S. Wishart B. N. Ametaj 《Metabolomics : Official journal of the Metabolomic Society》2018,14(6):83
Introduction
Metritis is an uterine pathology that causes economic losses for the dairy industry. It is associated with lower reproductive efficiency, increased culling rates, decreased milk production and increased veterinary costs.Objectives
To gain a more detailed view of the urine metabolome and to detect metabolite signature in cows with metritis. In addition, we aimed to identify early metabolites which can help to detect cows at risk to develop metritis in the future.Methods
We used nuclear magnetic resonance spectroscopy starting at 8 and 4 weeks prior to the expected day of parturition, during the week of diagnosis of metritis, and at 4 and 8 weeks after diagnosis of metritis in Holstein dairy cows.Results
At 8 weeks before parturition, pre-metritic cows had a total of 30 altered metabolites. Interestingly, 28 of them increased in urine when compared with control cows (P?<?0.05). At 4 weeks before parturition, 34 metabolites were altered. At the week of diagnosis of metritis a total of 20 metabolites were altered (P?<?0.05). The alteration continued at 4 and 8 weeks after diagnosis.Conclusions
The metabolic fingerprints in the urine of pre-metritic and metritic cows point toward excretion of multiple amino acids, tricarboxylic acid cycle metabolites and monosaccharides. Combination of galactose, leucine, lysine and panthotenate at 8 weeks before parturition might serve as predictive biomarkers for metritis.16.
André Homeyer Patrik Nasr Christiane Engel Stergios Kechagias Peter Lundberg Mattias Ekstedt Henning Kost Nick Weiss Tim Palmer Horst Karl Hahn Darren Treanor Claes Lundström 《Diagnostic pathology》2017,12(1):80
Background
Steatosis is routinely assessed histologically in clinical practice and research. Automated image analysis can reduce the effort of quantifying steatosis. Since reproducibility is essential for practical use, we have evaluated different analysis methods in terms of their agreement with stereological point counting (SPC) performed by a hepatologist.Methods
The evaluation was based on a large and representative data set of 970 histological images from human patients with different liver diseases. Three of the evaluated methods were built on previously published approaches. One method incorporated a new approach to improve the robustness to image variability.Results
The new method showed the strongest agreement with the expert. At 20× resolution, it reproduced steatosis area fractions with a mean absolute error of 0.011 for absent or mild steatosis and 0.036 for moderate or severe steatosis. At 10× resolution, it was more accurate than and twice as fast as all other methods at 20× resolution. When compared with SPC performed by two additional human observers, its error was substantially lower than one and only slightly above the other observer.Conclusions
The results suggest that the new method can be a suitable automated replacement for SPC. Before further improvements can be verified, it is necessary to thoroughly assess the variability of SPC between human observers.17.
Shayne Mason Karin Terburgh Roan Louw 《Metabolomics : Official journal of the Metabolomic Society》2018,14(6):74
Introduction
The analysis of limited-quantity samples remains a challenge associated with mouse models, especially for multi-platform metabolomics studies. Although inherently insensitive, the highly specific characteristics of nuclear magnetic resonance (NMR) spectroscopy make it an advantageous platform for global metabolite profiling, particularly in mitochondrial disease research.Objectives
Show method equivalency between a well-established standard operating protocol (SOP) and our novel miniaturized 1H-NMR method.Method
The miniaturized method was performed in a 2 mm NMR tube on a standard 500 MHz NMR spectrometer with a 5 mm triple-resonance inverse TXI probe at room temperature.Results
Firstly, using synthetic urine spiked with low (50 µM), medium (250 µM) and high (500 µM) levels (n?=?10) of nine standards, both the SOP and miniaturized method were shown to have acceptable precision (CV?<?15%), relative accuracy (80–120%), and linearity (R2?>?0.95), except for taurine. Furthermore, statistical equivalence was shown using the two one-sided test. Secondly, pooled mouse quadriceps muscle extract was used to further confirm method equivalence (n?=?3), as well as explore the analytical dynamics of this novel approach by analyzing more-concentrated versions of samples (up to 10× concentration) to expand identification of metabolites qualitatively, with quantitative linearity. Lastly, we demonstrate the new technique’s application in a pilot metabolomics study using minute soleus muscle tissue from a mouse model of Leigh syndrome using Ndufs4 KO mice.Conclusion
We demonstrate method equivalency, supporting our novel miniaturized 1H-NMR method as a financially feasible alternative to cryoprobe technology—for limited-quantity biological samples in metabolomics studies that requires a volume one-tenth of the SOP.18.
Andres Gil David Siegel Silke Bonsing-Vedelaar Hjalmar Permentier Dirk-Jan Reijngoud Frank Dekker Rainer Bischoff 《Metabolomics : Official journal of the Metabolomic Society》2017,13(1):1
Introduction
Boiling ethanol extraction is a frequently used method for metabolomics studies of biological samples. However, the stability of several central carbon metabolites, including nucleotide triphosphates, and the influence of the cellular matrix on their degradation have not been addressed.Objectives
To study how a complex cellular matrix extracted from yeast (Saccharomyces cerevisiae) may affect the degradation profiles of nucleotide triphosphates extracted under boiling ethanol conditions.Methods
We present a double-labelling LC–MS approach with a 13C-labeled yeast cellular extract as complex surrogate matrix, and 13C15N-labeled nucleotides as internal standards, to study the effect of the yeast matrix on the degradation of nucleotide triphosphates.Results
While nucleotide triphosphates were degraded to the corresponding diphosphates in pure solutions, degradation was prevented in the presence of the yeast matrix under typical boiling ethanol extraction conditions.Conclusions
Extraction of biological samples under boiling ethanol extraction conditions that rapidly inactivate enzyme activity are suitable for labile central energy metabolites such as nucleotide triphosphates due to the stabilizing effect of the yeast matrix. The basis of this phenomenon requires further study.Graphical abstract
19.
Christopher W. Armstrong Neil R. McGregor Donald P. Lewis Henry L. Butt Paul R. Gooley 《Metabolomics : Official journal of the Metabolomic Society》2017,13(1):8
Introduction
The human gut microbiota has the ability to modulate host metabolism. Metabolic profiling of the microbiota and the host biofluids may determine associations significant of a host–microbe relationship. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a long-term disorder of fatigue that is poorly understood, but has been linked to gut problems and altered microbiota.Objectives
Find changes in fecal microbiota and metabolites in ME/CFS and determine their association with blood serum and urine metabolites.Methods
A workflow was developed that correlates microbial counts with fecal, blood serum and urine metabolites quantitated by high-throughput 1H NMR spectroscopy. The study consists of thirty-four females with ME/CFS (34.9?±?1.8 SE years old) and twenty-five non-ME/CFS female (33.0?±?1.6 SE years old).Results
The workflow was validated using the non-ME/CFS cohort where fecal short chain fatty acids (SCFA) were associated with serum and urine metabolites indicative of host metabolism changes enacted by SCFA. In the ME/CFS cohort a decrease in fecal lactate and an increase in fecal butyrate, isovalerate and valerate were observed along with an increase in Clostridium spp. and a decrease in Bacteroides spp. These differences were consistent with an increase in microbial fermentation of fiber and amino acids to produce SCFA in the gut of ME/CFS patients. Decreased fecal amino acids positively correlated with substrates of gluconeogenesis and purine synthesis in the serum of ME/CFS patients.Conclusion
Increased production of SCFA by microbial fermentation in the gut of ME/CFS patients may be associated with deleterious effects on the host energy metabolism.20.
J. A. A. S. Jayaweera W. P. H. Abeydeera G. R. Ranasinghe 《Journal of medical case reports》2018,12(1):384