Urinary and faecal metabolic profiling have been extensively studied in gastrointestinal diseases as potential diagnostic markers, and to enhance our understanding of the intestinal microbiome in the ...pathogenesis these conditions. The impact of bowel cleansing on the microbiome has been investigated in several studies, but limited to just one study on the faecal metabolome.
To compare the effects of bowel cleansing on the composition of the faecal microbiome, and the urine and faecal metabolome.
Urine and faecal samples were obtained from eleven patients undergoing colonoscopy at baseline, and then at day 3 and week 6 after colonoscopy. 16S rRNA gene sequencing was used to analyse changes in the microbiome, and metabonomic analysis was performed using proton nuclear magnetic resonance (
H NMR) spectroscopy.
Microbiomic analysis demonstrated a reduction in alpha diversity (Shannon index) between samples taken at baseline and three days following bowel cleansing (p = 0.002), and there was no significant difference between samples at baseline and six weeks post colonoscopy. Targeted and non-targeted analysis of urinary and faecal bacterial associated metabolites showed no significant impact following bowel cleansing.
Bowel cleansing causes a temporary disturbance in bacterial alpha diversity measured in faeces, but no significant changes in the faecal and urine metabolic profiles, suggesting that overall the faecal microbiome and its associated metabolome is resistant to the effects of an induced osmotic diarrhoea.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Antibiotic-associated diarrhoea is among the most common adverse events related to antibiotic use. Most cases are mild, but Clostridium difficile infection causes a spectrum of disease, ranging from ...occasional diarrhoea to colitis, toxic megacolon, and potentially death. Recent developments in our understanding of the biology of the gut microbiota have provided new insights into the pathogenesis of these conditions, and have revealed a role for manipulation of the gut microbiota as a novel therapeutic approach. This review will give an overview of the assessment of these conditions, before focusing on the rapidly developing area of their treatment.
We report here the long‐term results of HLA‐mismatched kidney transplantation without maintenance immunosuppression (IS) in 10 subjects following combined kidney and bone marrow transplantation. All ...subjects were treated with nonmyeloablative conditioning and an 8‐ to 14‐month course of calcineurin inhibitor with or without rituximab. All 10 subjects developed transient chimerism, and in seven of these, IS was successfully discontinued for 4 or more years. Currently, four subjects remain IS free for periods of 4.5–11.4 years, while three required reinstitution of IS after 5–8 years due to recurrence of original disease or chronic antibody‐mediated rejection. Of the 10 renal allografts, three failed due to thrombotic microangiopathy or rejection. When compared with 21 immunologically similar living donor kidney recipients treated with conventional IS, the long‐term IS‐free survivors developed significantly fewer posttransplant complications. Although most recipients treated with none or two doses of rituximab developed donor‐specific antibody (DSA), no DSA was detected in recipients treated with four doses of rituximab. Although further revisions of the current conditioning regimen are planned in order to improve consistency of the results, this study shows that long‐term stable kidney allograft survival without maintenance IS can be achieved following transient mixed chimerism induction.
The authors evaluate the long‐term results of HLA‐mismatched kidney transplantation without maintenance immunosuppression in 10 subjects following combined kidney and bone marrow transplantation in comparison with 21 immunologically similar living donor kidney recipients who were treated with conventional immunosuppression.
Until recently, long‐range forecast systems showed only modest levels of skill in predicting surface winter climate around the Atlantic Basin and associated fluctuations in the North Atlantic ...Oscillation at seasonal lead times. Here we use a new forecast system to assess seasonal predictability of winter North Atlantic climate. We demonstrate that key aspects of European and North American winter climate and the surface North Atlantic Oscillation are highly predictable months ahead. We demonstrate high levels of prediction skill in retrospective forecasts of the surface North Atlantic Oscillation, winter storminess, near‐surface temperature, and wind speed, all of which have high value for planning and adaptation to extreme winter conditions. Analysis of forecast ensembles suggests that while useful levels of seasonal forecast skill have now been achieved, key sources of predictability are still only partially represented and there is further untapped predictability.
Key Points
The winter NAO can be skilfully predicted months ahead
The signal‐to‐noise ratio of the predictable signal is anomalously low
Predictions of the risk of regional winter extremes are possible
Low‐pressure catalyst: A novel dizinc complex (1) having a macrocyclic ancillary ligand shows remarkable activity for the copolymerization of carbon dioxide and cyclohexene oxide, at only one ...atmosphere of CO2. TON=turnover number; TOF=turnover frequency.
Background
The inflammatory bowel diseases (IBD), Crohn’s disease (CD), and ulcerative colitis (UC), are chronic inflammatory conditions of the gastrointestinal tract whose pathogenesis is not ...completely understood.
1
H nuclear magnetic resonance (NMR) spectroscopy of serum generates comprehensive metabolic profiles, reflecting systemic metabolism, which may be altered in disease states.
Aim
The aim of this study was to use
1
H NMR-based serum metabolic profiling in the investigation of CD patients, UC patients, and controls, potentially to provide insights into disordered metabolism in IBD, and into underlying mechanisms of disease.
Methods
Serum metabolic profiles were acquired from 67 individuals (24 CD patients, 20 UC patients, and 23 healthy controls). The multivariate pattern-recognition techniques of principal components analysis (PCA) and partial least squares discriminant analysis with orthogonal signal correction (OSC-PLS-DA) were used to investigate differences between cohorts.
Results
OSC-PLS-DA distinguished CD and UC cohorts with significant predictive accuracy, highlighting differences in lipid and choline metabolism. Metabolic profiles of both CD and UC cohorts, and the combined IBD cohort, differed significantly from controls: metabolites of importance in the OSC-PLS-DA models included lipoproteins (especially HDL cholesterol), choline,
N
-acetylglycoprotein, and amino acids.
Conclusions
1
H NMR-based metabolic profiling has identified distinct differences in serum metabolic phenotype between CD and UC patients, as well as between IBD patients and controls.
Fecal metabolites are being increasingly studied to unravel the host-gut microbial metabolic interactions. However, there are currently no guidelines for fecal sample collection and storage based on ...a systematic evaluation of the effect of time, storage temperature, storage duration, and sampling strategy. Here we derive an optimized protocol for fecal sample handling with the aim of maximizing metabolic stability and minimizing sample degradation. Samples obtained from five healthy individuals were analyzed to assess topographical homogeneity of feces and to evaluate storage duration-, temperature-, and freeze–thaw cycle-induced metabolic changes in crude stool and fecal water using a 1H NMR spectroscopy-based metabolic profiling approach. Interindividual variation was much greater than that attributable to storage conditions. Individual stool samples were found to be heterogeneous and spot sampling resulted in a high degree of metabolic variation. Crude fecal samples were remarkably unstable over time and exhibited distinct metabolic profiles at different storage temperatures. Microbial fermentation was the dominant driver in time-related changes observed in fecal samples stored at room temperature and this fermentative process was reduced when stored at 4 °C. Crude fecal samples frozen at −20 °C manifested elevated amino acids and nicotinate and depleted short chain fatty acids compared to crude fecal control samples. The relative concentrations of branched-chain and aromatic amino acids significantly increased in the freeze–thawed crude fecal samples, suggesting a release of microbial intracellular contents. The metabolic profiles of fecal water samples were more stable compared to crude samples. Our recommendation is that intact fecal samples should be collected, kept at 4 °C or on ice during transportation, and extracted ideally within 1 h of collection, or a maximum of 24 h. Fecal water samples should be extracted from a representative amount (∼15 g) of homogenized stool sample, aliquoted, and stored at <−20 °C, avoiding further freeze–thaw cycles.
Abstract
Background and Aims
The inflammatory bowel diseases IBD, Crohn’s disease and ulcerative colitis, are chronic, idiopathic gastrointestinal diseases. Although their precise aetiology is ...unknown, it is thought to involve a complex interaction between genetic predisposition and an abnormal host immune response to environmental exposures, probably microbial. Microbial dysbiosis has frequently been documented in IBD. Metabolomics the study of small molecular intermediates and end products of metabolism in biological samples provides a unique opportunity to characterize disease-associated metabolic changes and may be of particular use in quantifying gut microbial metabolism. Numerous metabolomic studies have been undertaken in IBD populations, identifying consistent alterations in a range of molecules across several biological matrices. This systematic review aims to summarize these findings.
Methods
A comprehensive, systematic search was carried out using Medline and Embase. All studies were reviewed by two authors independently using predefined exclusion criteria. Sixty-four relevant papers were assessed for quality and included in the review.
Results
Consistent metabolic perturbations were identified, including increases in levels of branched chain amino acids and lipid classes across stool, serum, plasma and tissue biopsy samples, and reduced levels of microbially modified metabolites in both urine such as hippurate and stool such as secondary bile acids samples.
Conclusions
This review provides a summary of metabolomic research in IBD to date, highlighting underlying themes of perturbed gut microbial metabolism and mammalian–microbial co-metabolism associated with disease status.
Faecal microbiota transplant (FMT) effectively treats recurrent
infection (rCDI), but its mechanisms of action remain poorly defined. Certain bile acids affect
germination or vegetative growth. We ...hypothesised that loss of gut microbiota-derived bile salt hydrolases (BSHs) predisposes to CDI by perturbing gut bile metabolism, and that BSH restitution is a key mediator of FMT's efficacy in treating the condition.
Using stool collected from patients and donors pre-FMT/post-FMT for rCDI, we performed 16S rRNA gene sequencing, ultra performance liquid chromatography mass spectrometry (UPLC-MS) bile acid profiling, BSH activity measurement, and qPCR of
/
CD genes involved in bile metabolism. Human data were validated in
batch cultures and a C57BL/6 mouse model of rCDI.
From metataxonomics, pre-FMT stool demonstrated a reduced proportion of BSH-producing bacterial species compared with donors/post-FMT. Pre-FMT stool was enriched in taurocholic acid (TCA, a potent
germinant); TCA levels negatively correlated with key bacterial genera containing BSH-producing organisms. Post-FMT samples demonstrated recovered BSH activity and
/
CD gene copy number compared with pretreatment (p<0.05). In batch cultures, supernatant from engineered
-expressing
and naturally BSH-producing organisms (
and
) reduced TCA-mediated
germination relative to culture supernatant of wild-type (BSH-negative)
total viable counts were ~70% reduced in an rCDI mouse model after administration of
expressing highly active BSH relative to mice administered BSH-negative
(p<0.05).
Restoration of gut BSH functionality contributes to the efficacy of FMT in treating rCDI.
Although Arctic tundra has been estimated to cover only 8% of the global land surface, the large and potentially labile carbon pools currently stored in tundra soils have the potential for large ...emissions of carbon (C) under a warming climate. These emissions as radiatively active greenhouse gases in the form of both CO2 and CH4 could amplify global warming. Given the potential sensitivity of these ecosystems to climate change and the expectation that the Arctic will experience appreciable warming over the next century, it is important to assess whether responses of C exchange in tundra regions are likely to enhance or mitigate warming. In this study we compared analyses of C exchange of Arctic tundra between 1990 and 2006 among observations, regional and global applications of process-based terrestrial biosphere models, and atmospheric inversion models. Syntheses of flux observations and inversion models indicate that the annual exchange of CO2 between Arctic tundra and the atmosphere has large uncertainties that cannot be distinguished from neutral balance. The mean estimate from an ensemble of process-based model simulations suggests that Arctic tundra has acted as a sink for atmospheric CO2 in recent decades, but based on the uncertainty estimates it cannot be determined with confidence whether these ecosystems represent a weak or a strong sink. Tundra was 0.6 °C warmer in the 2000s compared to the 1990s. The central estimates of the observations, process-based models, and inversion models each identify stronger sinks in the 2000s compared with the 1990s. Some of the process models indicate that this occurred because net primary production increased more in response to warming than heterotrophic respiration. Similarly, the observations and the applications of regional process-based models suggest that CH4 emissions from Arctic tundra have increased from the 1990s to 2000s because of the sensitivity of CH4 emissions to warmer temperatures. Based on our analyses of the estimates from observations, process-based models, and inversion models, we estimate that Arctic tundra was a sink for atmospheric CO2 of 110 Tg C yr−1 (uncertainty between a sink of 291 Tg C yr−1 and a source of 80 Tg C yr−1) and a source of CH4 to the atmosphere of 19 Tg C yr−1 (uncertainty between sources of 8 and 29 Tg C yr−1). The suite of analyses conducted in this study indicate that it is important to reduce uncertainties in the observations, process-based models, and inversions in order to better understand the degree to which Arctic tundra is influencing atmospheric CO2 and CH4 concentrations. The reduction of uncertainties can be accomplished through (1) the strategic placement of more CO2 and CH4 monitoring stations to reduce uncertainties in inversions, (2) improved observation networks of ground-based measurements of CO2 and CH4 exchange to understand exchange in response to disturbance and across gradients of climatic and hydrological variability, and (3) the effective transfer of information from enhanced observation networks into process-based models to improve the simulation of CO2 and CH4 exchange from Arctic tundra to the atmosphere.
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