scholarly journals Pathomechanisms of Oxidative Stress in Inflammatory Bowel Disease and Potential Antioxidant Therapies

2017 ◽  
Vol 2017 ◽  
pp. 1-18 ◽  
Author(s):  
Tian Tian ◽  
Ziling Wang ◽  
Jinhua Zhang
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Defense Mechanisms ◽  
Gastrointestinal Disease ◽  
Mucosal Immune Response ◽  
Stress Signaling ◽  
Substantial Progress ◽  
Inflammatory Bowel ◽  
Underlying Mechanisms

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease whose incidence has risen worldwide in recent years. Accumulating evidence shows that oxidative stress plays an essential role in the pathogenesis and progression of IBD. This review highlights the generation of reactive oxygen species (ROS) and antioxidant defense mechanisms in the gastrointestinal (GI) tract, the involvement of oxidative stress signaling in the initiation and progression of IBD and its relationships with genetic susceptibility and the mucosal immune response. In addition, potential therapeutic strategies for IBD that target oxidative stress signaling are reviewed and discussed. Though substantial progress has been made in understanding the role of oxidative stress in IBD in humans and experimental animals, the underlying mechanisms are still not well defined. Thus, further studies are needed to validate how oxidative stress signaling is involved in and contributes to the development of IBD.

scholarly journals Implications of Antioxidant Systems in Inflammatory Bowel Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Guiping Guan ◽  
Shile Lan
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Defense Mechanisms ◽  
Antioxidant Defense ◽  
Antioxidative Activity ◽  
Mucosal Immune Response ◽  
Antioxidant Systems ◽  
Critical Function ◽  
Inflammatory Bowel ◽  
High Level

The global incidence of inflammatory bowel disease (IBD), a group of chronic gastrointestinal disorders, has been rising. The preponderance of evidence demonstrates that oxidative stress (OS) performs a critical function in the onset of IBD and the manner of its development. The purpose of this review is to outline the generation of reactive oxygen species and antioxidant defense mechanisms in the gastrointestinal tract and the role played by OS in marking the onset and development of IBD. Furthermore, the review demonstrates the various ways through which OS is related to genetic susceptibility and the mucosal immune response. The experimental results suggest that certain therapeutic regimens for IBD could have a favorable impact by scavenging free radicals, reducing cytokine and prooxidative enzyme concentrations, and improving the antioxidative capabilities of cells. However, antioxidative activity characterized by a high level of specificity may be fundamental for the development of clinical therapies and for relapsing IBD patients. Therefore, additional research is required to clarify the ways through which OS is related to the pathogenesis and progression of IBD.

scholarly journals Multi-Omics Characterization of Inflammatory Bowel Disease-Induced Hyperplasia/Dysplasia in the Rag2−/−/Il10−/− Mouse Model

2020 ◽  
Vol 22 (1) ◽  
pp. 364
Author(s):  
Qiyuan Han ◽  
Thomas J. Y. Kono ◽  
Charles G. Knutson ◽  
Nicola M. Parry ◽  
Christopher L. Seiler ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Gastrointestinal Disease ◽  
Tumor Development ◽  
Proximal Colon ◽  
Helicobacter Hepaticus ◽  
Reduced Representation ◽  
Reduced Representation Bisulfite Sequencing ◽  
Inflammatory Bowel

Epigenetic dysregulation is hypothesized to play a role in the observed association between inflammatory bowel disease (IBD) and colon tumor development. In the present work, DNA methylome, hydroxymethylome, and transcriptome analyses were conducted in proximal colon tissues harvested from the Helicobacter hepaticus (H. hepaticus)-infected murine model of IBD. Reduced representation bisulfite sequencing (RRBS) and oxidative RRBS (oxRRBS) analyses identified 1606 differentially methylated regions (DMR) and 3011 differentially hydroxymethylated regions (DhMR). These DMR/DhMR overlapped with genes that are associated with gastrointestinal disease, inflammatory disease, and cancer. RNA-seq revealed pronounced expression changes of a number of genes associated with inflammation and cancer. Several genes including Duox2, Tgm2, Cdhr5, and Hk2 exhibited changes in both DNA methylation/hydroxymethylation and gene expression levels. Overall, our results suggest that chronic inflammation triggers changes in methylation and hydroxymethylation patterns in the genome, altering the expression of key tumorigenesis genes and potentially contributing to the initiation of colorectal cancer.

37 Monitoring the evolution of inflammatory bowel disease (IBD) in pediatric and adult cohorts of patients to identify biomarkers to predict cancer risk

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A38-A38
Author(s):  
Shilpa Ravindran ◽  
Heba Sidahmed ◽  
Harshitha Manjunath ◽  
Rebecca Mathew ◽  
Tanwir Habib ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Mesenchymal Transition ◽  
Increased Risk ◽  
Hamad Medical Corporation ◽  
Inflammatory Bowel ◽  
Left And Right

BackgroundPatients with inflammatory bowel disease (IBD) have increased risk of developing colorectal cancer (CRC), depending on the duration and severity of the disease. The evolutionary process in IBD is driven by chronic inflammation leading to epithelial-to-mesenchymal transition (EMT) events in colonic fibrotic areas. EMT plays a determinant role in tumor formation and progression, through the acquisition of ‘stemness’ properties and the generation of neoplastic cells. The aim of this study is to monitor EMT/cancer initiating tracts in IBD in association with the deep characterization of inflammation in order to assess the mechanisms of IBD severity and progression towards malignancy.Methods10 pediatric and 20 adult IBD patients, admitted at Sidra Medicine (SM) and Hamad Medical Corporation (HMC) respectively, have been enrolled in this study, from whom gut tissue biopsies (from both left and right side) were collected. Retrospectively collected tissues (N=10) from patients with malignancy and history of IBD were included in the study. DNA and RNA were extracted from fresh small size (2–4 mm in diameter) gut tissues using the BioMasher II (Kimble) and All Prep DNA/RNA kits (Qiagen). MicroRNA (miRNA; N=700) and gene expression (N=800) profiling have been performed (cCounter platform; Nanostring) as well as the methylation profiling microarray (Infinium Methylation Epic Bead Chip kit, Illumina) to interrogate up to 850,000 methylation sites across the genome.ResultsDifferential miRNA profile (N=27 miRNA; p<0.05) was found by the comparison of tissues from pediatric and adult patients. These miRNAs regulate: i. oxidative stress damage (e.g., miR 99b), ii. hypoxia induced autophagy; iii. genes associated with the susceptibility to IBD (ATG16L1, NOD2, IRGM), iv. immune responses, such as TH17 T cell subset (miR 29). N=6 miRNAs (miR135b, 10a196b, 125b, let7c, 375) linked with the regulation of Wnt/b-catenin, EM-transaction, autophagy, oxidative stress and play role also in cell proliferation and mobilization and colorectal cancer development were differentially expressed (p<0.05) in tissues from left and right sides of gut. Gene expression signature, including genes associated with inflammation, stemness and fibrosis, has also been performed for the IBD tissues mentioned above. Methylation sites at single nucleotide resolution have been analyzed.ConclusionsAlthough the results warrant further investigation, differential genomic profiling suggestive of altered pathways involved in oxidative stress, EMT, and of the possible stemness signature was found. The integration of data from multiple platforms will provide insights of the overall molecular determinants in IBD patients along with the evolution of the disease.Ethics ApprovalThis study was approved by Sidra Medicine and Hamad Medical Corporation Ethics Boards; approval number 180402817 and MRC-02-18-096, respectively.

Evaluation of Effect CAT -262C/T, SOD + 35A/C, GPx1 Pro197Leu Polymorphisms in Patients with IBD in the Polish Population

2016 ◽  
Vol 88 (6) ◽  
Author(s):  
Jerzy Mrowicki ◽  
Małgorzata Mrowicka ◽  
Ireneusz Majsterek ◽  
Michał Mik ◽  
Adam Dziki ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Antioxidant Enzymes ◽  
Bowel Disease ◽  
Protective Effects ◽  
Polish Population ◽  
Nucleotide Polymorphisms ◽  
Inflammatory Bowel ◽  
Genotype C

AbstractInflammatory bowel disease (IBD) are a heterogeneous group of disorders in the course dominated by chronic, recurrent gastrointestinal inflammation. It is believed that the activation of IBD occurs in patients with a genetic predisposition to their development. Chronic inflammation develops as a result of an excessive reaction of the immune system principally under the influence of environmental risk factors. Among them, it has been shown that the mechanism of oxidative stress is associated with the pathophysiology of inflammatory bowel disease, responsible for the commencement and progress of these diseases.was the relationship between single nucleotide polymorphisms (SNPs) of individual antioxidant enzymes, and the prevalence of inflammatory bowel disease that may be associated with increased levels of oxidative stress.A total of 111 IBD patients, including 65 patients with ulcerative colitis (UC) and 46 with Crohn’s disease (CD) and 125 healthy controls recruited from the Polish population, were genotyped forThe performed analysis of genetic polymorphisms of antioxidant enzymes showed that polymorphic variant of the CAT -262 C / T may have protective effects in patients with ulcerative colitis in the range of genotype C / T; OR = 0.49 (0.25-0.99), p = 0.044. Trend protective, but statistically unrelated, it was also observed for genotype T / T and T allele of the same polymorphism and genotypes and allelesIt has been shown that the polymorphism of antioxidant enzymes

scholarly journals Mucosa-Associated Faecalibacterium prausnitzii Phylotype Richness Is Reduced in Patients with Inflammatory Bowel Disease

2015 ◽  
Vol 81 (21) ◽  
pp. 7582-7592 ◽  
Author(s):  
Mireia Lopez-Siles ◽  
Margarita Martinez-Medina ◽  
Carles Abellà ◽  
David Busquets ◽  
Miriam Sabat-Mir ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
16S Rrna ◽  
16S Rrna Gene ◽  
Bowel Disease ◽  
Denaturing Gradient Gel Electrophoresis ◽  
Gastrointestinal Disease ◽  
Rrna Gene ◽  
Content Type ◽  
Faecalibacterium Prausnitzii ◽  
Inflammatory Bowel

ABSTRACTFaecalibacterium prausnitziidepletion in intestinal diseases has been extensively reported, but little is known about intraspecies variability. This work aims to determine if subjects with gastrointestinal disease host mucosa-associatedF. prausnitziipopulations different from those hosted by healthy individuals. A new species-specific PCR-denaturing gradient gel electrophoresis (PCR-DGGE) method targeting the 16S rRNA gene was developed to fingerprintF. prausnitziipopulations in biopsy specimens from 31 healthy control (H) subjects and 36 Crohn's disease (CD), 23 ulcerative colitis (UC), 6 irritable bowel syndrome (IBS), and 22 colorectal cancer (CRC) patients. The richness ofF. prausnitziisubtypes was lower in inflammatory bowel disease (IBD) patients than in H subjects. The most prevalent operational taxonomic units (OTUs) consisted of four phylotypes (OTUs with a 99% 16S rRNA gene sequence similarity [OTU99]), which were shared by all groups of patients. Their distribution and the presence of some disease-specificF. prausnitziiphylotypes allowed us to differentiate the populations in IBD and CRC patients from that in H subjects. At the level of a minimum similarity of 97% (OTU97), two phylogroups accounted for 98% of the sequences. Phylogroup I was found in 87% of H subjects but in under 50% of IBD patients (P= 0.003). In contrast, phylogroup II was detected in >75% of IBD patients and in only 52% of H subjects (P= 0.005). This study reveals that even though the main members of theF. prausnitziipopulation are present in both H subjects and individuals with gut diseases, richness is reduced in the latter and an altered phylotype distribution exists between diseases. This approach may serve as a basis for addressing the suitability ofF. prausnitziiphylotypes to be quantified as a putative biomarker of disease and depicting the importance of the loss of these subtypes in disease pathogenesis.

scholarly journals CCR6–CCL20-Mediated Immunologic Pathways in Inflammatory Bowel Disease

2018 ◽  
Vol 1 (1) ◽  
pp. 15-29 ◽  
Author(s):  
Ranmali Ranasinghe ◽  
Rajaraman Eri
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Systematic Investigation ◽  
Protective Mechanism ◽  
Food Antigens ◽  
Gut Mucosa ◽  
T Helper Lymphocyte ◽  
Inflammatory Bowel ◽  
Underlying Mechanisms

Inflammatory bowel disease (IBD) has evoked significant interest in human immunobiology given its tactical immune evasion methodologies resulting in acute immune destabilization. IBD comprising Crohn’s disease and Ulcerative colitis manifests as chronic inflammation in the gut mucosa, leading to complexities involving immune dysregulation in the T helper lymphocyte arm, effecting disease pathogenicity. The mucosa of the alimentary canal is constantly exposed to a myriad of food antigens and luminal microorganisms for which a consistent host-protective mechanism is operative in healthy people. Lowered mucosal immune expression which allows penetration of the epithelial barrier by infective pathogenic microbes elicits both innate and adaptive immune responses in the gut, culminating in aberrant intestinal inflammation. Interestingly, the IBD leukocyte repertoire is significantly entwined with chemokine-assisted chemotactic navigation into the sites of inflammation, which is also thought to generate favorable immune-suppressive responses. The functions of the cognate chemokine receptor, CCR6, which binds with its unique ligand CCL20, are expected to tilt the balance between upregulation of homeostatic tolerance and inflammatory pathophysiology. This review aims to critically examine the CCR6-driven immune pathways: TH1/TH2, TH1/TH17, TH17/Treg, IL-23/IL-17, Akt/ERK-1/2, ILC3, and TH9/TH2 for systematic investigation of its underlying mechanisms in the future and to underpin its importance in resolving IBD pathology. Thus, CCR6 occupies an exclusive position in gut immunology which renders it an invaluable therapeutic tool for the production of novel medicaments to treat IBD.

scholarly journals Oxidative Stress and Redox-Modulating Therapeutics in Inflammatory Bowel Disease

2020 ◽  
Vol 26 (11) ◽  
pp. 1034-1046 ◽  
Author(s):  
Arno R. Bourgonje ◽  
Martin Feelisch ◽  
Klaas Nico Faber ◽  
Andreas Pasch ◽  
Gerard Dijkstra ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Inflammatory Bowel

scholarly journals The Role of Long-Chain Fatty Acids in Inflammatory Bowel Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Chunxiang Ma ◽  
Reshma Vasu ◽  
Hu Zhang
Keyword(s):  
Inflammatory Bowel Disease ◽  
Fatty Acids ◽  
Bowel Disease ◽  
Mucosal Healing ◽  
Long Chain Fatty Acids ◽  
Inflammatory Bowel ◽  
Underlying Mechanisms ◽  
Long Chain ◽  
Chain Fatty Acids

Inflammatory bowel disease (IBD) is a complicated disease involving multiple pathogenic factors. The complex relationships between long-chain fatty acids (LCFAs) and the morbidity of IBD drive numerous studies to unravel the underlying mechanisms. A better understanding of the role of LCFAs in IBD will substitute or boost the current IBD therapies, thereby obtaining mucosal healing. In this review, we focused on the roles of LCFAs on the important links of inflammatory regulation in IBD, including in the pathogen recognition phase and in the inflammatory resolving phase, and the effects of LCFAs on immune cells in IBD.

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