Exploring metabolic biomarkers and regulation pathways of acute pancreatitis using ultra-performance liquid chromatography combined with a mass spectrometry-based metabolomics strategy

Guo, Jiajia; Li, Xuesong; Wang, Donghong; Guo, Yuekun; Cao, Ting

doi:10.1039/c9ra02186h

Cited by 10 publications

(8 citation statements)

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“…Pancreatic disease is closely associated with the down-regulation of valine. Furthermore, the pathway underlying the biosynthesis of valine is involved in the pathogenesis of acute pancreatitis [ 24 ]. In addition, valine is a component of pancreatic juice [ 30 ]; pancreatic insufficiency might be responsible for valine reductions.…”

Section: Resultsmentioning

confidence: 99%

“…Over the past few years, metabolomics has been used to identify the etiology of acute pancreatitis [ 22 ] and judge the severity of this disease [ 23 ]. In addition, metabolomics has become a potential tool to differentiate acute pancreatitis from chronic pancreatitis, and pancreatic cancer, as well as other diseases of the digestive system [ 24 – 28 ]. For example, Huang et al distinguished three types of acute pancreatitis (biliary acute pancreatitis, hyperlipidemia acute pancreatitis, alcoholic acute pancreatitis) by gas chromatography-mass spectrometry-based metabolomics [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, only a few metabolomics studies have focused on pancreatitis. Furthermore, these previous studies were more focused on differences between inflammatory and healthy samples, rather than between severe and mild cases, and were often limited to small clinical sample sizes or based on animal models [ 22 , 24 ]. Moreover, to the best of our knowledge, no previous study has applied metabolomics analysis to plasma EVs to study acute pancreatitis.…”

Section: Introductionmentioning

confidence: 99%

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Quantitative metabolic analysis of plasma extracellular vesicles for the diagnosis of severe acute pancreatitis

Lou

Shi

et al. 2022

J Nanobiotechnol

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Background Severe acute pancreatitis (SAP) is the most common gastrointestinal disease and is associated with unpredictable seizures and high mortality rates. Despite improvements in the treatment of acute pancreatitis, the timely and accurate diagnosis of SAP remains highly challenging. Previous research has shown that extracellular vesicles (EVs) in the plasma have significant potential for the diagnosis of SAP since the pancreas can release EVs that carry pathological information into the peripheral blood in the very early stages of the disease. However, we know very little about the metabolites of EVs that might play a role in the diagnosis of SAP. Methods Here, we performed quantitative metabolomic analyses to investigate the metabolite profiles of EVs isolated from SAP plasma. We also determined the metabolic differences of EVs when compared between healthy controls, patients with SAP, and those with mild acute pancreatitis (MAP). Results A total of 313 metabolites were detected, mainly including organic acids, amino acids, fatty acids, and bile acids. The results showed that the metabolic composition of EVs derived from SAP and MAP was significantly different from those derived from healthy controls and identified specific differences between EVs derived from patients with SAP and MAP. On this basis, we identified four biomarkers from plasma EVs for SAP detection, including eicosatrienoic acid (C20:3), thiamine triphosphate, 2-Acetylfuran, and cis-Citral. The area under the curve (AUC) was greater than 0.95 for both discovery (n = 30) and validation (n = 70) sets. Conclusions Our data indicate that metabolic profiling analysis of plasma EVs and the screening of potential biomarkers are of significant potential for improving the early diagnosis and severity differentiation of acute pancreatitis. Graphical abstract

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Quantitative metabolic analysis of plasma extracellular vesicles for the diagnosis of severe acute pancreatitis

Lou

Shi

et al. 2022

J Nanobiotechnol

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“… 2017 ; Guo et al. 2019 ). Succinate, an intermediate in the Krebs cycle, can stabilize hypoxia-inducible factor-1 and stimulate dendritic cells to mediate inflammation (Mills and O'Neill 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Qingyi granules ameliorate severe acute pancreatitis in rats by modulating the gut microbiota and serum metabolic aberrations

Jiao,

Liu,

Luo

et al. 2023

Pharmaceutical Biology

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Context Qingyi granules can be used to effectively treat patients with severe acute pancreatitis (SAP). Objective To elucidate the role of gut microbiota-mediated metabolism in the therapeutic effects of Qingyi granules. Materials and methods Sprague–Dawley rats were grouped into the sham operation, SAP model, Qingyi granule intervention (Q, 1.8 g/kg) and emodin intervention (E, 50 mg/kg) groups and observed for 24 h. H&E staining and ELISA were used for histopathological analysis and serum enzyme and cytokine assays. 16S rDNA sequencing and UHPLC-HRMS were used for gut microbiota analysis and untargeted metabolomics. Results In SAP rats, Qingyi granules decreased the pancreatic pathological score (Q, 7.4 ± 1.14; SAP, 11.6 ± 1.14, p < 0.01); serum amylase (Q, 121.2 ± 6.7; SAP, 144.3 ± 8.86, p < 0.05), lipase (Q, 566 ± 20.34; SAP, 656.7 ± 29.32, p < 0.01), and diamineoxidase (Q, 492.8 ± 26.08; SAP, 566.1 ± 26.83, p < 0.05) activities; and IL-1β (Q, 29.48 ± 0.88; SAP, 36.17 ± 1.88, p < 0.01), IL-6 (Q, 112.2 ± 3.57; SAP, 128.9 ± 9.09, p < 0.05) and TNF-α (Q, 215.3 ± 8.67; SAP, 266.4 ± 28.03, p < 0.05) levels. SAP induced Helicobacter and Lactobacillus overgrowth and suppressed Romboutsia and Allobaculum growth and caused aberrations in bacterial metabolites, which were partly reversed by Qingyi granules. Discussion and Conclusions Qingyi granules can modulate the gut microbiota and metabolic abnormalities to ameliorate SAP. Multi-omics approaches allow systematic study of the pharmacological mechanisms of compound prescriptions for critical illnesses.

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“…Studies of progressive chronic Pt in swine ( Sun et al, 2014 ) and rat ( Tian et al, 2015 ) models showed gradual decreases in PC, GPC, betaine and glycine in the swine model, and changes in aspartate, betaine and lipids, which in the rat model correlated with the degree of fibrosis and/or inflammatory cell infiltration. GC-MS profiling of tissue extracts and serum ( Sakai et al, 2012 ) in mice with acute induced Pt showed significant changes in tricarboxylic acid (TCA) cycle intermediates, glutamate and O- phosphoethanolamine, whereas serum profiling using Ultra Performance Liquid Chromatography (UPLC)-MS suggested that a 19-metabolite signature could distinguish animals with acute Pt from controls ( Guo et al, 2019 ). Recent studies in human subjects have also reported potential blood markers that could distinguish chronic pancreatitis from PDA ( Lindahl et al, 2017 ; Mayerle et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Metabolic profiling of induced acute pancreatitis and pancreatic cancer progression in a mutant Kras mouse model

Carneiro

Pinto

Serrao

et al. 2022

Front. Mol. Biosci.

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Untargeted Nuclear Magnetic Resonance (NMR) metabolomics of polar extracts from the pancreata of a caerulin-induced mouse model of pancreatitis (Pt) and of a transgenic mouse model of pancreatic cancer (PCa) were used to find metabolic markers of Pt and to characterize the metabolic changes accompanying PCa progression. Using multivariate analysis a 10-metabolite metabolic signature specific to Pt tissue was found to distinguish the benign condition from both normal tissue and precancerous tissue (low grade pancreatic intraepithelial neoplasia, PanIN, lesions). The mice pancreata showed significant changes in the progression from normal tissue, through low-grade and high-grade PanIN lesions to pancreatic ductal adenocarcinoma (PDA). These included increased lactate production, amino acid changes consistent with enhanced anaplerosis, decreased concentrations of intermediates in membrane biosynthesis (phosphocholine and phosphoethanolamine) and decreased glycosylated uridine phosphates, reflecting activation of the hexosamine biosynthesis pathway and protein glycosylation.

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Exploring metabolic biomarkers and regulation pathways of acute pancreatitis using ultra-performance liquid chromatography combined with a mass spectrometry-based metabolomics strategy

Abstract: Acute pancreatitis (AP), as a common kind of pancreas-based inflammatory disease, is accompanied by a serious and abnormal metabolism.

Cited by 10 publications

References 50 publications

Quantitative metabolic analysis of plasma extracellular vesicles for the diagnosis of severe acute pancreatitis

Quantitative metabolic analysis of plasma extracellular vesicles for the diagnosis of severe acute pancreatitis

Qingyi granules ameliorate severe acute pancreatitis in rats by modulating the gut microbiota and serum metabolic aberrations

Metabolic profiling of induced acute pancreatitis and pancreatic cancer progression in a mutant Kras mouse model

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