scholarly journals New Insights into Inflammatory Bowel Diseases from Proteomic and Lipidomic Studies

Proteomes ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 18
Author(s):  
Serena Longo ◽  
Marcello Chieppa ◽  
Luca G. Cossa ◽  
Chiara C. Spinelli ◽  
Marco Greco ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Biomarker Discovery ◽  
Intestinal Inflammation ◽  
Clinical Symptoms ◽  
Great Promise ◽  
Reactive Protein ◽  
Bowel Diseases ◽  
Technological Developments ◽  
Intestinal Microbial Flora ◽  
Inflammatory Bowel

Ulcerative colitis (UC) and Crohn’s disease (CD) represent the two main forms of chronic inflammatory bowel diseases (IBD). The exact IBD etiology is not yet revealed but CD and UC are likely induced by an excessive immune response against normal constituents of the intestinal microbial flora. IBD diagnosis is based on clinical symptoms often combined with invasive and costly procedures. Thus, the need for more non-invasive markers is urgent. Several routine laboratory investigations have been explored as indicators of intestinal inflammation in IBD, including blood testing for C-reactive protein, erythrocyte sedimentation rate, and specific antibodies, in addition to stool testing for calprotectin and lactoferrin. However, none has been universally adopted, some have been well-characterized, and others hold great promise. In recent years, the technological developments within the field of mass spectrometry (MS) and bioinformatics have greatly enhanced the ability to retrieve, characterize, and analyze large amounts of data. High-throughput research allowed enhancing the understanding of the biology of IBD permitting a more accurate biomarker discovery than ever before. In this review, we summarize currently used IBD serological and stool biomarkers and how proteomics and lipidomics are contributing to the identification of IBD biomarkers.

scholarly journals P040 Proteomic characterisation of serum extracellular vesicles in patients with inflammatory bowel diseases: a novel approach for biomarker discovery

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S152-S153
Author(s):  
M Chaparro ◽  
M Azkargorta ◽  
A Lapitz ◽  
L Ortega-Moreno ◽  
I Iloro ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Inflammatory Bowel Diseases ◽  
Biomarker Discovery ◽  
Intestinal Inflammation ◽  
Protein Quantification ◽  
Differentially Expressed ◽  
Mass Spectrometry Analysis ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Independent Cohort

Abstract Background Our aim was to identify novel biomarkers and molecular pathways that may be involved in the development or progression of inflammatory bowel diseases (IBD) by the comparison of serum extracellular vesicles (EVs) proteomic profile between healthy controls (HC), Crohn’s disease (CD) [active (aCD) and quiescent (qCD)] and ulcerative colitis (UC) [active (aUC) and quiescent (qUC)] patients. Methods A total of 150 individuals with an ileocolonoscopy performed the same day of blood collection were included: 30 HC, 30 aCD, 30 qCD, 30 aUC and 30 qUC. Severity of inflammation was rated based on the Simple Endoscopic Score (SES-CD) in CD and the endoscopic subscore of the Mayo index in UC. Serum EVs were isolated from blood serum and their size, distribution and concentration were determined by nanoparticle tracking analysis with NanoSight LM10 (Malvern, UK). The presence of EVs positive and negative markers were evaluated by immunoblotting. Proteomic differential analysis was performed by Label Free nLC tandem mass spectrometry analysis by nanoACQUITY UPLC (Waters) coupled on-line to a LTQ Orbitrap XL (Thermo Electron, Bremen, Germany). Peptide identification was performed by Mascot (MatrixScience, London, UK) against Uniprot/Swissprot DataBase, and protein quantification by Progenesis LC-MS (Nonlinear Dynamics Ltd., Newcastle upon Tyne, UK). Proteins matching at least two unique peptides were considered for the analysis. Proteins with p ≤ 0.05 and ratio >1.5 in any sense were considered deregulated. Proteomic results and clinical data were further integrated for biomarker discovery. Proteins with p-value cross-validation <0.05 and accuracy ≥0.65 individually or in combination with another molecule were considered to have potential as biomarkers. Results EVs size and concentration are shown in Table 1. There were not differences in EVs concentration and size between groups (Figure 1). A total of 324 proteins were identified, being some of them differentially expressed in different conditions (Table 2). Several proteins met the criteria to be proposed as accurate biomarkers: 17 in UC vs. HC, 9 in aUC vs. HC, 3 in qUC vs. HC, 13 in CD vs. HC, 16 in aCD vs. HC and 14 in qCD vs. HC. These proteins are involved in relevant processes in IBD pathogenesis such as angiogenesis, cell migration, immune response, acute phase response, inflammation and coagulation. Finally, a panel of seven proteins was chosen for validation in an independent cohort (Table 3). Conclusion Serum EVs of patients with IBD (CD and UC) carry differentially expressed proteins compared with HC and also depending on the presence of intestinal inflammation. These proteins are promising biomarkers of IBD that will be validated in an independent cohort. M. Chaparro and M. Azkargorta have equally contributed as first authors. F. Elortza and J.P. Gisbert have equally contributed as senior authors.

Anti-TNF-α Treatment Reduces the Baseline Procoagulant Imbalance of Patients With Inflammatory Bowel Diseases

2021 ◽  
Author(s):  
Armando Tripodi ◽  
Luisa Spina ◽  
Laura Francesca Pisani ◽  
Lidia Padovan ◽  
Flaminia Cavallaro ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Coagulation Factors ◽  
Infliximab Treatment ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Thrombosis Risk ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Factor Α

Abstract Background Inflammatory bowel diseases (IBD) are characterized by an increased thrombosis risk of uncertain etiology. Coagulation derangement arising from inflammation may be a triggering factor. We hypothesized that strong inflammation inhibitors (eg, anti-tumor necrosis factor-α drugs) may affect coagulation. Methods Forty patients with IBD were compared with 57 control patients for coagulation factors and endogenous thrombin potential (ETP), the latter being the most sensitive marker of in vivo pro- and anticoagulation balance. We measured ETP in the presence and absence of thrombomodulin (the physiologic protein C [PC] activator). Coagulation at different timepoints was also assessed for 28 of these patients during infliximab treatment. Results The median ETP (nM thrombin × minutes) and range (minimum-maximum) were each higher in patients at baseline than in control patients in both the absence (2120 [1611-3041] vs 1865 [1270-2337]) and the presence (1453 [464-2522] vs 831 [104-1741]) of thrombomodulin. The ETP ratio (with/without thrombomodulin) was high at baseline (0.73 [0.21-0.90] vs 0.45 [0.07-0.85]). The ETP and ETP ratio declined during treatment and were significantly lower at the end than at baseline. Factor (F) VIII and fibrinogen, which were high at baseline, decreased during treatment and at the end were significantly lower than at baseline. The FVIII/PC ratio, which was high in patients at baseline, declined during treatment and at the end was lower than at baseline. C-reactive protein recorded at the end of treatment was lower than at baseline. Conclusions Patients with IBD have a procoagulant imbalance as shown by increased ETP at baseline. The ETP decreases during treatment with infliximab, which is related to decreased FVIII and FVIII/PC ratio. This effect is also related to the improvement of inflammation as shown by decreased fibrinogen and C-reactive protein.

scholarly journals Imaging in Inflammatory Bowel Diseases - Magnetic Resonance Imaging

2015 ◽  
Vol 33 (Suppl. 1) ◽  
pp. 26-31
Author(s):  
Hans Herfarth ◽  
Andreas G. Schreyer
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Intestinal Inflammation ◽  
Imaging Modality ◽  
Imaging Techniques ◽  
Magnetization Transfer ◽  
Diagnostic Value ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Line Imaging ◽  
Sensitivity Specificity

Diagnostic imaging techniques play an important role in the diagnosis and management of patients with inflammatory bowel diseases (IBDs). The approach should be guided by considerations of diagnostic accuracy, concerns about patient exposure to ionizing radiation, local expertise and tolerance of the endoscopic and/or imaging technique. In regard to the clinical diagnostic value (sensitivity, specificity and accuracy), no significant differences exist between CT and MRI for the evaluation of the extent of inflammation, stricturing, penetrating disease or extraluminal complications such as abscesses. Due to the absence of radiation exposure, MRI of the intestine is recommended as the first-line imaging modality in patients with suspected or established IBD. The focus of this review is the latest developments in MRI techniques to detect IBDs. Specifically, the use of new indices for the grading of inflammation or assessing bowel damage as well as innovative experimental approaches such as diffusion-weighted imaging or magnetization-transfer MRI to evaluate and quantify the degree of intestinal inflammation and fibrosis in stricturing Crohn's disease are discussed.

Oral Supplementation With Selected Lactobacillus Acidophilus Triggers Antimicrobial Response, Activation of Innate Lymphoid Cells Type 3 And Improves Colitis

2021 ◽  
Author(s):  
Jiří Hrdý ◽  
Aurélie Couturier-Maillard ◽  
Denise Boutillier ◽  
Carmen Lapadatescu ◽  
Philippe Blanc ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Lactobacillus Acidophilus ◽  
Target Genes ◽  
Intestinal Inflammation ◽  
Probiotic Strain ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Trinitrobenzene Sulfonic Acid ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Abstract Live biotherapeutic products constitute an emerging therapeutic approach to prevent or treat inflammatory bowel diseases. Lactobacillus acidophilus is a constituent of the human microbiota with probiotic potential, that are illustrated by direct and indirect antimicrobial activity against several pathogens and improvement of intestinal inflammation. In this study, we evaluated the anti-inflammatory properties of the L. acidophilus strain BIO5768 and assessed the underlying mechanisms of action. BIO5768 was able to counteract the acute colitis that is induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). When administered alone or in combination with Bifidobacterium animalis spp. lactis BIO5764 and Limosilactobacillus reuteri, BIO5768 was also able to alleviate intestinal inflammation induced by Citrobacter rodentium infection. Supplementation of naïve mice with either strain BIO5768 alone or as mixture, increased the gene expression of several target genes involved in immune signaling, including c-type lectin Reg3 gamma. Consistently, the ability of innate lymphoid cells to secrete IL-22 was enhanced in response to BIO5768. Interestingly, the aforementioned responses were shown to be independent of NOD2 and Th17 signaling in mice that were mono-colonized with BIO5768. In conclusion, we identify a new potential probiotic strain with the ability for the management of inflammatory bowel diseases, and provide some insights into its mode of action.

scholarly journals Microbiota-independent immunological effects of non-digestible oligosaccharides in the context of inflammatory bowel diseases

2020 ◽  
Vol 79 (4) ◽  
pp. 468-478 ◽  
Author(s):  
Stefania Del Fabbro ◽  
Philip C. Calder ◽  
Caroline E. Childs
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Immune Cell ◽  
Intestinal Inflammation ◽  
Mechanisms Of Action ◽  
Mucosal Inflammation ◽  
Disease States ◽  
Inflammatory Conditions ◽  
Bowel Diseases ◽  
Inflammatory Bowel

The aim of the present paper is to review the effects of non-digestible oligosaccharides (NDO) on immunity, focusing on their microbiota-independent mechanisms of action, as well as to explore their potential beneficial role in inflammatory bowel diseases (IBD). IBD are chronic, inflammatory conditions of the gastrointestinal tract. Individuals with IBD have an aberrant immune response to commensal microbiota, resulting in extensive mucosal inflammation and increased intestinal permeability. NDO are prebiotic fibres well known for their role in supporting intestinal health through modulation of the gut microbiota. NDO reach the colon intact and are fermented by commensal bacteria, resulting in the production of SCFA with immunomodulatory properties. In disease states characterised by increased gut permeability, prebiotics may also bypass the gut barrier and directly interact with intestinal and systemic immune cells, as demonstrated in patients with IBD and in infants with an immature gut. In vitro models show that fructooligosaccharides, inulin and galactooligosaccharides exert microbiota-independent effects on immunity by binding to toll-like receptors on monocytes, macrophages and intestinal epithelial cells and by modulating cytokine production and immune cell maturation. Moreover, animal models and human supplementation studies demonstrate that some prebiotics, including inulin and lactulose, might reduce intestinal inflammation and IBD symptoms. Although there are convincing preliminary data to support NDO as immunomodulators in the management of IBD, their mechanisms of action are still unclear and larger standardised studies need to be performed using a wider range of prebiotics.

scholarly journals The Multifaceted Role of the Inflammasome in Inflammatory Bowel Diseases

2011 ◽  
Vol 11 ◽  
pp. 1536-1547 ◽  
Author(s):  
Donata Lissner ◽  
Britta Siegmund
Keyword(s):  
Inflammatory Bowel Disease ◽  
Inflammatory Bowel Diseases ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Inflammasome Activation ◽  
Specific Cell ◽  
Epithelial Regeneration ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Inflammasomes are intracellular multiprotein complexes that coordinate the maturation of interleukin (IL)-1β and IL-18 in response to pathogens and metabolic danger. Both cytokines have been linked to intestinal inflammation. However, recently evolving concepts ascribe a major role to the inflammasome in maintaining intestinal homeostasis. This review recapitulates its position in the development of inflammatory bowel disease, thereby outlining a model in which hypo- as well as hyperfunctionality can lead to an imbalance of the system, depending on the specific cell population affected. In the epithelium, the inflammasome is essential for regulation of permeability and epithelial regeneration through sensing of commensal microbes, while excessive inflammasome activation within the lamina propria contributes to severe intestinal inflammation.

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