Alterations in Lipid, Amino Acid, and Energy Metabolism Distinguish Crohn Disease from Ulcerative Colitis and Control Subjects by Serum Metabolomic Profiling
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ABSTRACT:
ORGANISM(S): Homo Sapiens
TISSUE(S): Blood
DISEASE(S): Inflammatory Bowel Disease
PROVIDER: ST000899 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
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Project description:IntroductionBiomarkers are needed in inflammatory bowel disease (IBD) to help define disease activity and identify underlying pathogenic mechanisms. We hypothesized that serum metabolomics, which produces unique metabolite profiles, can aid in this search.ObjectivesThe aim of this study was to characterize serum metabolomic profiles in patients with IBD, and to assess for differences between patients with ulcerative colitis (UC), Crohn's disease (CD), and non- IBD subjects.MethodsSerum samples from 20 UC, 20 CD, and 20 non-IBD control subjects were obtained along with patient characteristics, including medication use and clinical disease activity. Non-targeted metabolomic profiling was performed using ultra-high performance liquid chromatography/mass spectrometry (UPLC-MS/MS) optimized for basic or acidic species and hydrophilic interaction liquid chromatography (HILIC/UPLC-MS/MS).ResultsIn total, 671 metabolites were identified. Comparing IBD and control subjects revealed 173 significantly altered metabolites (27 increased and 146 decreased). The majority of the alterations occurred in lipid-, amino acid-, and energy-related metabolites. Comparing only CD and control subjects revealed 286 significantly altered metabolites (54 increased and 232 decreased), whereas comparing UC and control subjects revealed only 5 significantly altered metabolites (all decreased). Hierarchal clustering using significant metabolites separated CD from UC and control subjects.ConclusionsWe demonstrate that a number of lipid-, amino acid-, and tricarboxylic acid (TCA) cycle- related metabolites were significantly altered in IBD patients, more specifically in CD. Therefore, alterations in lipid and amino acid metabolism and energy homeostasis may play a key role in the pathogenesis of CD.
| S-EPMC5907923 | biostudies-literature
Project description:IBS: Patients who have undergone a diagnostic program for gastrointestinal symptoms and where the diagnosis irritable bowel syndrome was reached. UC: Patients with well-diagnosed ulcerative colitis Keywords: other
2005-04-01 | GSE2461 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-04-01 | GSE107597 | GEO
Project description:The potential association between altered levels of plasma free amino acids (PFAAs) and uric acid (UA) with estimated glomerular filtration rate (eGFR) remains unknown among patients with hypertension. A total of 2804 healthy controls and 2455 hypertensive patients were included in the current analysis. eGFR was defined as reduced when it was <60 ml/min/1.73 m2. The associations between reduced eGFR and individual PFAAs and UA in the healthy control and hypertension groups were explored by logistic regression analyses adjusted for potential confounding variables. Results show that UA had a significant positive association with reduced eGFR in both healthy control and hypertension groups (P < 0.001). Among the PFAAs, citrulline, glycine and phenylalanine showed significant positive associations with reduced eGFR in both healthy control (P < 0.01 to 0.001) and hypertension (P < 0.001) groups. Moreover, alanine, asparagine and methionine achieved significant positive associations with reduced eGFR only in the hypertension group (P < 0.01 to 0.001). Conversely, serine showed significant inverse associations with reduced eGFR in the hypertension group only (P < 0.001). Our findings provide first evidence for a strong relationship between distinct patterns of PFAAs and elevated UA with reduced eGFR in hypertension. The findings may appear useful in developing effective strategies for the prevention or early detection and treatment of declined kidney function in hypertension.
| S-EPMC6635408 | biostudies-literature
Project description:The prevalence of metabolic syndrome is increasing worldwide, especially in Asian populations. Early detection and effective intervention are vital. Plasma free amino acid profile is a potential biomarker for the early detection for lifestyle-related diseases. However, little is known about whether the altered plasma free amino acid profiles in subjects with metabolic syndrome are related to the effectiveness of dietary and exercise interventions.Eighty-five Japanese subjects who fulfilled the Japanese diagnostic criteria for metabolic syndrome were enrolled in a 3-month diet and exercise intervention. The plasma free amino acid concentrations and metabolic variables were measured, and the relationships between plasma free amino acid profiles, metabolic variables and the extent of body weight reduction were investigated. Those who lost more than 3% of body weight were compared with those who lost less than 3%.Baseline levels of most amino acids in the subset that went on to lose <3% body weight were markedly lower compared with the counterpart, although both groups showed similar proportional pattern of plasma amino acid profiles. The weight loss induced by the diet and exercise intervention normalized plasma free amino acid profiles. For those with a high degree of weight loss, those changes were also associated with improvement in blood pressure, triglyceride and hemoglobin A1c levels.These data suggest that among Japanese adults meeting the criteria for metabolic syndrome, baseline plasma free amino acid profiles may differ in ways that predict who will be more vs less beneficially responsive to a standard diet and exercise program. Plasma free amino acid profiles may also be useful as markers for monitoring the risks of developing lifestyle-related diseases and measuring improvement in physiological states.
| S-EPMC4775824 | biostudies-other
Project description:We used microarrays to detail the global gene expression of inflamed vs non-inflamed colon tissue from UC subjects
2018-04-01 | GSE107499 | GEO
Project description:BACKGROUND Abdominal aortic aneurysm (AAA) is a complicated aortic dilatation disease. Metabolomics is an emerging system biology method. This aim of this study was to identify abnormal metabolites and metabolic pathways associated with AAA and to discover potential biomarkers that could affect the size of AAAs. MATERIAL AND METHODS An untargeted metabolomic method was used to analyze the plasma metabolic profiles of 39 patients with AAAs and 30 controls. Multivariate analysis methods were used to perform differential metabolite screening and metabolic pathway analysis. Cluster analysis and univariate analysis were performed to identify potential metabolites that could affect the size of an AAA. RESULTS Forty-five different metabolites were identified with an orthogonal projection to latent squares-discriminant analysis model and the differences between them in the patients with AAAs and the control group were compared. A variable importance in the projection score >1 and P<0.05 were considered statistically significant. In patients with AAAs, the pathways involving metabolism of alanine, aspartate, glutamate, D-glutamine, D-glutamic acid, arginine, and proline; tricarboxylic acid cycling; and biosynthesis of arginine are abnormal. The progression of an AAA may be related to 13 metabolites: citric acid, 2-oxoglutarate, succinic acid, coenzyme Q1, pyruvic acid, sphingosine-1-phosphate, platelet-activating factor, LysoPC (16: 00), lysophosphatidylcholine (18: 2(9Z,12Z)/0: 0), arginine, D-aspartic acid, and L- and D-glutamine. CONCLUSIONS An untargeted metabolomic analysis using ultraperformance liquid chromatography-tandem mass spectrometry identified metabolites that indicate disordered metabolism of energy, lipids, and amino acids in AAAs.
| S-EPMC7718721 | biostudies-literature
Project description:Atherosclerosis is a leading cause of cardiovascular disease (CVD), but the effect of diet on the atherosclerotic heart's metabolism is unclear. We used an integrated metabolomics and lipidomics approach to evaluate metabolic perturbations in heart and serum from mice fed an atherogenic diet (AD) for 8, 16, and 25 weeks. Nuclear magnetic resonance (NMR)-based metabolomics revealed significant changes in sulfur amino acid (SAA) and lipid metabolism in heart from AD mice compared with heart from normal diet mice. Higher SAA levels in AD mice were quantitatively verified using liquid chromatography-mass spectrometry (LC/MS). Lipidomic profiling revealed that fatty acid and triglyceride (TG) levels in the AD group were altered depending on the degree of unsaturation. Additionally, levels of SCD1, SREBP-1, and PPARγ were reduced in AD mice after 25 weeks, while levels of reactive oxygen species were elevated. The results suggest that a long-term AD leads to SAA metabolism dysregulation and increased oxidative stress in the heart, causing SCD1 activity suppression and accumulation of toxic TGs with a low degree of unsaturation. These findings demonstrate that the SAA metabolic pathway is a promising therapeutic target for CVD treatment and that metabolomics can be used to investigate the metabolic signature of atherosclerosis.
| S-EPMC5648757 | biostudies-literature
Project description:ObjectiveThe pathogenesis of UC relates to gut microbiota dysbiosis. We postulate that alterations in the viral community populating the intestinal mucosa play an important role in UC pathogenesis. This study aims to characterise the mucosal virome and their functions in health and UC.DesignDeep metagenomics sequencing of virus-like particle preparations and bacterial 16S rRNA sequencing were performed on the rectal mucosa of 167 subjects from three different geographical regions in China (UC=91; healthy controls=76). Virome and bacteriome alterations in UC mucosa were assessed and correlated with patient metadata. We applied partition around medoids clustering algorithm and classified mucosa viral communities into two clusters, referred to as mucosal virome metacommunities 1 and 2.ResultsIn UC, there was an expansion of mucosa viruses, particularly Caudovirales bacteriophages, and a decrease in mucosa Caudovirales diversity, richness and evenness compared with healthy controls. Altered mucosal virome correlated with intestinal inflammation. Interindividual dissimilarity between mucosal viromes was higher in UC than controls. Escherichia phage and Enterobacteria phage were more abundant in the mucosa of UC than controls. Compared with metacommunity 1, metacommunity 2 was predominated by UC subjects and displayed a significant loss of various viral species. Patients with UC showed substantial abrogation of diverse viral functions, whereas multiple viral functions, particularly functions of bacteriophages associated with host bacteria fitness and pathogenicity, were markedly enriched in UC mucosa. Intensive transkingdom correlations between mucosa viruses and bacteria were significantly depleted in UC.ConclusionWe demonstrated for the first time that UC is characterised by substantial alterations of the mucosa virobiota with functional distortion. Enrichment of Caudovirales bacteriophages, increased phage/bacteria virulence functions and loss of viral-bacterial correlations in the UC mucosa highlight that mucosal virome may play an important role in UC pathogenesis.
| S-EPMC6582748 | biostudies-literature