scholarly journals Mucosal Metabolomic Profiling and Pathway Analysis Reveal the Metabolic Signature of Ulcerative Colitis

Metabolites ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 291 ◽  
Author(s):  
Joseph Diab ◽  
Terkel Hansen ◽  
Rasmus Goll ◽  
Hans Stenlund ◽  
Einar Jensen ◽  
...  

The onset of ulcerative colitis (UC) is characterized by a dysregulated mucosal immune response triggered by several genetic and environmental factors in the context of host–microbe interaction. This complexity makes UC ideal for metabolomic studies to unravel the disease pathobiology and to improve the patient stratification strategies. This study aims to explore the mucosal metabolomic profile in UC patients, and to define the UC metabolic signature. Treatment- naïve UC patients (n = 18), UC patients in deep remission (n = 10), and healthy volunteers (n = 14) were recruited. Mucosa biopsies were collected during colonoscopies. Metabolomic analysis was performed by combined gas chromatography coupled to time-of-flight mass spectrometry (GC-TOF-MS) and ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS). In total, 177 metabolites from 50 metabolic pathways were identified. The most prominent metabolome changes among the study groups were in lysophosphatidylcholine, acyl carnitine, and amino acid profiles. Several pathways were found perturbed according to the integrated pathway analysis. These pathways ranged from amino acid metabolism (such as tryptophan metabolism) to fatty acid metabolism, namely linoleic and butyrate. These metabolic changes during UC reflect the homeostatic disturbance in the gut, and highlight the importance of system biology approaches to identify key drivers of pathogenesis which prerequisite personalized medicine.

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S130-S131
Author(s):  
J Diab ◽  
T Hansen ◽  
R Goll ◽  
H Stenlund ◽  
E Jensen ◽  
...  

Abstract Background The onset of ulcerative colitis (UC) is characterised by a dysregulated mucosal immune response triggered by several genetic and environmental factors in the context of host-microbe interaction. This complexity makes UC ideal for metabolomic studies to unravel the disease pathobiology and to improve the patient stratification strategies toward personalised medicine. This study aims to explore the mucosal metabolomic profile in treatment-naïve and deep remission UC patients, and to define the metabolic signature of UC. Methods Treatment-naive UC patients (n = 18), UC patients in deep remission (n = 10), and healthy volunteers (n = 14) were recruited. Mucosa biopsies were collected during colonoscopy. The UC activity and the state of deep remission were assessed by endoscopy, histology, and by measuring TNF gene expression. Metabolomic analysis was performed by combined gas chromatography coupled to time-of-flight mass spectrometry (GC-TOF-MS) and ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS). In total, 177 metabolites from 50 metabolic pathways were identified. Results Multivariate data analysis revealed a distinct metabolomic profile in inflamed mucosa taken from treatment- naïve UC patients compared with non-inflamed mucosa taken from UC remission patients and healthy controls. The mucosal metabolome in UC remission patients differed to a lesser extent from the healthy controls. The most prominent metabolome changes among the study groups were in lysophosphatidylcholine, acylcarnitine, and amino acid profiles. Several metabolic pathways were perturbed, ranging from amino acid metabolism (such as tryptophan metabolism, and alanine, aspartate and glutamate metabolism) to antioxidant defence pathway (glutathione pathway). Furthermore, the pathway analysis revealed a disruption in the long-and short-chain fatty acid (LCFA and SCFA) metabolism, namely linoleic metabolism and butyrate metabolism. Conclusion The mucosal metabolomic profiling revealed a metabolic signature during the onset of UC, and reflected the homeostatic disturbance in the gut. The altered metabolic pathways highlight the importance of system biology approaches to identify key drivers of IBD pathogenesis which prerequisite personalised treatment.


2021 ◽  
Vol 22 (19) ◽  
pp. 10488
Author(s):  
Awraris Derbie Assefa ◽  
Seong-Hoon Kim ◽  
Vimalraj Mani ◽  
Hyoung-Rai Ko ◽  
Bum-Soo Hahn

The cyst nematodes Heterodera schachtii and Heterodera trifolii, whose major hosts are sugar beet and clover, respectively, damage a broad range of plants, resulting in significant economic losses. Nematodes synthesize metabolites for organismal development and social communication. We performed metabolic profiling of H. schachtii and H. trifolii in the egg, juvenile 2 (J2), and female stages. In all, 392 peaks were analyzed by capillary electrophoresis time-of-flight mass spectrometry, which revealed a lot of similarities among metabolomes. Aromatic amino acid metabolism, carbohydrate metabolism, choline metabolism, methionine salvage pathway, glutamate metabolism, urea cycle, glycolysis, gluconeogenesis, coenzyme metabolism, purine metabolism, pyrimidine metabolism, and tricarboxylic acid (TCA) cycle for energy conversion (β-oxidation and branched-chain amino acid metabolism) energy storage were involved in all stages studied. The egg and female stages synthesized higher levels of metabolites compared to the J2 stage. The key metabolites detected were glycerol, guanosine, hydroxyproline, citric acid, phosphorylcholine, and the essential amino acids Phe, Leu, Ser, and Val. Metabolites, such as hydroxyproline, acetylcholine, serotonin, glutathione, and glutathione disulfide, which are associated with growth and reproduction, mobility, and neurotransmission, predominated in the J2 stage. Other metabolites, such as SAM, 3PSer, 3-ureidopropionic acid, CTP, UDP, UTP, 3-hydroxy-3-methylglutaric acid, 2-amino-2-(hydroxymethyl-1,3-propanediol, 2-hydroxy-4-methylvaleric acid, Gly Asp, glucuronic acid-3 + galacturonic acid-3 Ser-Glu, citrulline, and γ-Glu-Asn, were highly detected in the egg stage. Meanwhile, nicotinamide, 3-PG, F6P, Cys, ADP-Ribose, Ru5P, S7P, IMP, DAP, diethanolamine, p-Hydroxybenzoic acid, and γ-Glu-Arg_divalent were unique to the J2 stage. Formiminoglutamic acid, nicotinaminde riboside + XC0089, putrescine, thiamine 2,3-dihydroxybenzoic acid, 3-methyladenine, caffeic acid, ferulic acid, m-hydrobenzoic acid, o- and p-coumaric acid, and shikimic acid were specific to the female stage. Overall, highly similar identities and quantities of metabolites between the corresponding stages of the two species of nematode were observed. Our results will be a valuable resource for further studies of physiological changes related to the development of nematodes and nematode–plant interactions.


Food Research ◽  
2020 ◽  
Vol 4 (S1) ◽  
pp. 133-138 ◽  
Author(s):  
N.S.M. Ali ◽  
A.R. Zabidi ◽  
M.N.A. Manap ◽  
S.M.S.N.S. Zahari ◽  
N. Yahaya

Islamic study defined Halal meat as a “thoyyiban” (clean) food source. Halal meat is produced by following slaughtering procedure as determined by the Islamic jurisprudence. Slaughtering methods have gained a worldwide discussion as animal welfare becomes a concern. However, there is lacking of scientific facts to prove which slaughtering methods produce better physiological effects on animals from metabolomics view. Therefore, metabolomics approach by Liquid Chromatography-Time of Flight-Mass Spectrometry (LC-TOF-MS) was used in this study to understand how the metabolites in poultry change when subjected to different slaughtering processes. The broiler chickens were subjected to Halal (Islamic tradition) and non-Halal slaughtering method (neck poking) where pectoral major muscle tissues from the slaughtered meat were selected for UHPLC-TOF-MS analysis. Metabolome data highlighted multiple pathways affected by slaughtering methods including glucose, amino acid, inosine, hypoxanthine and arginine. Higher utilization of energy in non-Halal slaughtering process was observed as indicated by the increase of gluconeogenesis and amino acid breakdown. The result from this study indicated that the method of slaughter affects the metabolites profile of poultry.


2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Dunfang Wang ◽  
Xuran Ma ◽  
Shanshan Guo ◽  
Yanli Wang ◽  
Tao Li ◽  
...  

As a classic prescription, Huangqin Tang (HQT) has been widely applied to treat ulcerative colitis (UC), although its pharmacological mechanisms are not clear. In this study, urine metabolomics was first analysed to explore the therapeutic mechanisms of HQT in UC rats induced by TNBS. We identified 28 potential biomarkers affected by HQT that might cause changes in urine metabolism in UC rats, mapped the network of metabolic pathways, and revealed how HQT affects metabolism of UC rats. The results showed that UC affects amino acid metabolism and biosynthesis of unsaturated fatty acids and impairs the tricarboxylic acid cycle (TCA cycle). UC induced inflammatory and gastrointestinal reactions by inhibiting the transport of fatty acids and disrupting amino acid metabolism. HQT plays key roles via regulating the level of biomarkers in the metabolism of amino acids, lipids, and so on, normalizing metabolic disorders. In addition, histopathology and other bioinformatics analysis further confirm that HQT altered UC rat physiology and pathology, ultimately affecting metabolic function of UC rats.


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