Ulcerative colitis: Recent advances in the understanding of disease pathogenesis

Porter, Ross J; Kalla, Rahul; Ho, Gwo–Tzer

doi:10.12688/f1000research.20805.1

Cited by 165 publications

(135 citation statements)

References 123 publications

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“…UC is consider as a disease of unknown aetiology, which is a multifactorial disorder ( Shen et al, 2018 ; Kaur and Goggolidou, 2020 ). It has been reported that a variety of complex factors including genetics, environment, epithelial barrier defects and immune system disorders were related to the pathogenesis of ulcerative colitis ( Porter et al, 2020 ). Meanwhile, abundant evidence have demonstrated that gut microbiota might play a crucial role in ulcerative colitis, and many studies have revealed that biodiversity and composition of gut microbiota were changed in UC patients and animal models ( Bajer et al, 2017 ; Shang et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Gut Microbiota and Related Metabolites Were Disturbed in Ulcerative Colitis and Partly Restored After Mesalamine Treatment

et al. 2021

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Mesalamine has been well used in the improvement of ulcerative colitis (UC) in clinics, however, the underlying mechanisms were not well illustrated. To explore its efficacy from the perspective of gut microbiota and related metabolites, we employed 16S rRNA sequencing and metabolomics approaches in stool samples across 14 normal healthy controls (NC group), 10 treatment-naïve UC patients (UC group) and 14 UC patients responded to mesalamine treatment (mesalamine group). We noted that the gut microbiota diversity and community composition were remarkably perturbed in UC group and partially restored by mesalamine treatment. The relative abundance of 192 taxa in genus level were significantly changed in UC group, and 168 genera were significantly altered after mesalamine intervention. Meanwhile, a total of 127 metabolites were significantly changed in UC group and 129 metabolites were significantly altered after mesalamine treatment. Importantly, we observed that many candidates including 49 genera (such as Escherichia-shigella, Enterococcus and Butyricicoccus) and 102 metatoblites (such as isoleucine, cholic acid and deoxycholic acid) were reversed by mesalamine. Spearman correlation analysis revealed that most of the candidates were significantly correlated with Mayo score of UC, and the relative abundance of specific genera were significant correlated with the perturbation of metabolites. Pathway analysis demonstrated that genera and metabolites candidates were enriched in many similar molecular pathways such as amino acid metabolism and secondary metabolites biosynthesis. Importantly, ROC curve analysis identified a gut microbiota signature composed of five genera including Escherichia-Shigella, Streptococcus, Megamonas, Prevotella_9 and [Eubacterium] _coprostanoligenes _group which might be used to distinguish UC group from both NC and mesalamine group. In all, our results suggested that mesalamine might exert a beneficial role in UC by modulating gut microbiota signature with correlated metabolites in different pathways, which may provide a basis for developing novel candidate biomarkers and therapeutic targets of UC.

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Section: Introductionmentioning

confidence: 99%

Gut Microbiota and Related Metabolites Were Disturbed in Ulcerative Colitis and Partly Restored After Mesalamine Treatment

et al. 2021

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“…PPAR-γ is an important negative regulator of colon inflammation [ 1 , 2 ] and is highly expressed in the colonic epithelium [ 3 ]. Therefore, we investigated whether TQ modulates colonic epithelial PPAR-γ both at protein and mRNA expression levels ( Figure 4 e,f).…”

Section: Resultsmentioning

confidence: 99%

“…Inflammatory bowel disease (IBD) covers a broad category of debilitating disorders that comprises Crohn’s disease (CD), which associates any segment of the gastrointestinal tract, and ulcerative colitis (UC), which involves only the colon (large intestine) and rectum [ 1 ]. To date, the exact cause of IBD and its pathogenesis is not entirely understood but appears to be multifactorial [ 2 ]. IBD is suggested to result from an uncontrolled immune response in genetically prone individuals, with environmental factors playing a triggering role [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Thymoquinone, a Dietary Bioactive Compound, Exerts Anti-Inflammatory Effects in Colitis by Stimulating Expression of the Colonic Epithelial PPAR-γ Transcription Factor

et al. 2021

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Inflammatory bowel diseases (IBD) are chronic inflammatory disorders with increasing incidence and prevalence worldwide. Here, we investigated thymoquinone (TQ), a naturally occurring phytochemical present in Nigella sativa, for anti-inflammatory effects in colonic inflammation. To address this, we used in vivo (mice) and in vitro (HT-29 cells) models in this investigation. Our results showed that TQ treatment significantly reduced the disease activity index (DAI), myeloperoxidase (MPO) activity, and protected colon microscopic architecture. In addition, TQ also reduced the expression of proinflammatory cytokines and mediators at both the mRNA and protein levels. Further, TQ decreased phosphorylation of the activated mitogen-activated protein kinase (MAPK) signaling pathway and nuclear factor kappa B (NF-κB) proteins and enhanced colon epithelial PPAR-γ transcription factor expression. TQ significantly decreased proinflammatory chemokines (CXCL-1 and IL-8), and mediator (COX-2) mRNA expression in HT-29 cells treated with TNF-α. TQ also increased HT-29 PPAR-γ mRNA, PPAR-γ protein expression, and PPAR-γ promoter activity. These results indicate that TQ inhibits MAPK and NF-κB signaling pathways and transcriptionally regulates PPAR-γ expression to induce potent anti-inflammatory activity in vivo and in vitro models of colon inflammation.

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“…Epidemiological analyses raise concerns regarding the increased incidence of patients with in ammatory bowel disease (IBD) worldwide; the incidence is estimated to have increased more than 2-fold in selected industrialized countries of the Western world between 2010 and 2030, thus representing global IBD burden 1 . Ulcerative colitis (UC) is an IBD, characterized by in ammation and ulceration of the mucosa limited to the colorectum in patients with repeated relapse and remission; it leads to adverse effects on the quality of life of the patients and the risk of colon cancer 2,3 . The disease activity of UC is assessed by clinical, biochemical, endoscopic, or histologic analyses, and remission at each level has been discussed to achieve therapeutic goals, that is, mucosal healing 4 .…”

Section: Introductionmentioning

confidence: 99%

Characteristics of Colon Crypt Stem Cells in Preserved Epithelial Cell Clumps in Dextran Sulfate Sodium-induced Mouse Model of Ulcerative Colitis

Kobayashi

Yamashita

Ichikawa

et al. 2021

Preprint

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Crypt stem cells rescue the colorectum from refractory ulcers in ulcerative colitis (UC). We previously reported that clumps of a few epithelial cells were scattered in ulcer regions in a dextran sulfate sodium (DSS)-induced mouse model of UC; however, the origin of the clumps is unknown. We determined the immunohistochemical expression of stem-cell markers in the epithelial clumps in female Balb/c mice administered DSS in drinking water for 6 days, followed by withdrawal of DSS for 6 days. Similar to the characteristics of UC, the ulcers were more severe in the distal region close to the anus than in the proximal region of the colorectum. Quantitative analyses revealed that the epithelial clumps appeared in relation to the severity of ulcer, and they expressed the cell adhesion molecules E-cadherin and β-catenin. Among stem cell markers, the epithelial clumps primarily expressed + 5 cell marker Dll1, followed by + 4 cell marker Bmi1 and crypt stem cell marker Lgr5 in that order. Nuclear expression of Sox9, but not Ki-67 and β-catenin was identified in the clumps. The present results suggest that the epithelial clumps comprised crypt-derived stem cells with the potential to regenerate crypts, which could serve as a potential treatment strategy for UC.

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Ulcerative colitis: Recent advances in the understanding of disease pathogenesis

Cited by 165 publications

References 123 publications

Gut Microbiota and Related Metabolites Were Disturbed in Ulcerative Colitis and Partly Restored After Mesalamine Treatment

Gut Microbiota and Related Metabolites Were Disturbed in Ulcerative Colitis and Partly Restored After Mesalamine Treatment

Thymoquinone, a Dietary Bioactive Compound, Exerts Anti-Inflammatory Effects in Colitis by Stimulating Expression of the Colonic Epithelial PPAR-γ Transcription Factor

Characteristics of Colon Crypt Stem Cells in Preserved Epithelial Cell Clumps in Dextran Sulfate Sodium-induced Mouse Model of Ulcerative Colitis

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