Monitoring of intestinal inflammation and prediction of recurrence in ulcerative colitis

The gut microbiome has been implicated in a range of diseases and there is a rapidly growing understanding of this ecosystem’s importance in inflammatory bowel disease. We are yet to identify a single microbe that causes either ulcerative colitis (UC) or pouchitis, however, reduced microbiome diversity is increasingly recognised in active UC. Manipulating the gut microbiome through dietary interventions, prebiotic and probiotic compounds and faecal microbiota transplantation may expand the therapeutic landscape in UC. Specific diets, such as the Mediterranean diet or diet rich in omega-3 fatty acids, may reduce intestinal inflammation or potentially reduce the risk of incident UC. This review summarises our knowledge of gut microbiome therapies in UC and pouchitis.

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Mouse model of ulcerative colitis using trinitrobenzene sulfonic acid

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v10i4.25351 ◽

2015 ◽

Vol 10 (4) ◽

pp. 860

Author(s):

Irfan Ahmad Rather ◽

Vivek K. Bajpai ◽

Nam Gyeong-Jun

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Mouse Model ◽

Bowel Disease ◽

Sulfonic Acid ◽

Intestinal Inflammation ◽

Cost Effective ◽

Trinitrobenzene Sulfonic Acid ◽

Clinical Presentations ◽

Inflammatory Bowel

Animal model of intestinal inflammation is of paramount significance that aids in discerning the pathologies underlying ulcerative colitis and Crohn’s disease, the two clinical presentations of inflammatory bowel disease. The 2,4,6-trinitrobenzene sulfonic acid (TNBS) colitis model represents one such intestinal inflammation-prototype that is generated in susceptible strains of mice through intra-rectal instillation of compound TNBS. In this paper, we demonstrate the experimental induction of TNBS-mediated colitis in a susceptible strain of ICR mice. This can be done by the following steps: a) acclimation, b) induction and c) observation. TNBS-mouse model provides the information in shortest possible time and simultaneously represents a cost effective and highly reproducible model method of studying the pathogenesis of inflammatory bowel disease.Video Clips<a href="https://youtube.com/v/6MsuIGzH3uA">Acclimation and induction of TNBS</a>: 4.5 min<a href="https://youtube.com/v/ya66SNwoVag">Observation and drug administration</a>: 1.5 min

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Physiological Basis for Novel Drug Therapies Used to Treat the Inflammatory Bowel Diseases I. Immunology and therapeutic potential of antiadhesion molecule therapy in inflammatory bowel disease

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00423.2004 ◽

2005 ◽

Vol 288 (2) ◽

pp. G169-G174 ◽

Cited By ~ 56

Author(s):

Gert Van Assche ◽

Paul Rutgeerts

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Adhesion Molecules ◽

Bowel Disease ◽

Intestinal Inflammation ◽

Therapeutic Potential ◽

Physiological Basis ◽

Inflammatory Bowel

Adhesion molecules regulate the influx of leukocytes in normal and inflamed gut. They are also involved in local lymphocyte stimulation and antigen presentation within the intestinal mucosa. In intestinal inflammation, many adhesion molecules are upregulated, but α4-integrins most likely hold a key position in directing leukocytes into the inflamed bowel wall. Therapeutic compounds directed against trafficking of leukocytes have been designed and are being developed as a novel class of drugs in the treatment of Crohn's disease and ulcerative colitis. This review deals with the immunological aspects of leukocyte trafficking focused on gut homing of T cells. Second, the changes in adhesion molecules and T cell trafficking during intestinal inflammation are discussed. Finally, we review the clinical data that have been gathered with respect to the therapeutic potential and the safety of antiadhesion molecule treatment. Antegren, or natalizumab, a humanized anti-α4 integrin IgG4 antibody, has been most extensively evaluated and may be close to registration. A more specific humanized α4β7-integrin MLN-02 has shown preliminary clinical efficacy in ulcerative colitis, and both antergren and MLN-02 appear to be very safe. Trials with the anti-ICAM-1 antisense oligonucleotide ISIS-2302 in steroid refractory Crohn's disease have provided conflicting efficacy data. In the near future, some of these novel biological agents may prove valuable therapeutic tools in the management of refractory inflammatory bowel disease, although it is too early to define the patient population that will benefit most from these agents.

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P852 A metabolomics approach to discover biomarkers of chronic intestinal inflammation associated with gut microbiota dysbiosis in ulcerative colitis and Celiac Disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjx180.979 ◽

2018 ◽

Vol 12 (supplement_1) ◽

pp. S547-S548 ◽

Cited By ~ 5

Author(s):

S Sitkin ◽

T Vakhitov ◽

E Tkachenko ◽

E Avalueva ◽

L Oreshko ◽

...

Keyword(s):

Ulcerative Colitis ◽

Celiac Disease ◽

Gut Microbiota ◽

Intestinal Inflammation ◽

Chronic Intestinal Inflammation ◽

Gut Microbiota Dysbiosis

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Growth differentiation factor 11 ameliorates experimental colitis by inhibiting NLRP3 inflammasome activation

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00159.2018 ◽

2018 ◽

Vol 315 (6) ◽

pp. G909-G920 ◽

Cited By ~ 4

Author(s):

Lanju Wang ◽

Yaohui Wang ◽

Zhenfeng Wang ◽

Yu Qi ◽

Beibei Zong ◽

...

Keyword(s):

Ulcerative Colitis ◽

Nlrp3 Inflammasome ◽

Intestinal Inflammation ◽

Experimental Colitis ◽

Inflammasome Activation ◽

Acute Colitis ◽

Pyrin Domain ◽

Differentiation Factor ◽

Nlrp3 Inflammasome Activation ◽

Receptor Family

Growth differentiation factor 11 (GDF11) has an anti-inflammatory effect in the mouse model of atherosclerosis and Alzheimer's disease, but how GDF11 regulates intestinal inflammation during ulcerative colitis (UC) is poorly defined. The Nod-like receptor family pyrin domain-1 containing 3 (NLRP3) inflammasome is closely associated with intestinal inflammation because of its ability to increase IL-1β secretion. Our aim is to determine whether GDF11 has an effect on attenuating experimental colitis in mice. In this study, using a dextran sodium sulfate (DSS)-induced acute colitis mouse model, we reported that GDF11 treatment attenuated loss of body weight, the severity of the disease activity index, shortening of the colon, and histological changes in the colon. GDF11 remarkably suppressed IL-1β secretion and NLRP3 inflammasome activation in colon samples and RAW 264.7 cells, such as the levels of NLRP3 and activated caspase-1. Furthermore, we found that GDF11 inhibited NLRP3 inflammasome activation by downregulating the Toll-like receptor 4/NF-κB p65 pathway and reactive oxygen species production via the typical Smad2/3 pathway. Thus, our research shows that GDF11 alleviates DSS-induced colitis by inhibiting NLRP3 inflammasome activation, providing some basis for its potential use in the treatment of UC. NEW & NOTEWORTHY Here, we identify a new role for growth differentiation factor 11 (GDF11), which ameliorates dextran sodium sulfate-induced acute colitis. Meanwhile, we discover a new phenomenon of GDF11 inhibiting IL-1β secretion and Nod-like receptor family pyrin domain-1 containing 3 (NLRP3) inflammasome activation. These findings reveal that GDF11 is a new potential candidate for the treatment of ulcerative colitis patients with a hyperactive NLRP3 inflammasome.

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Desmethylbellidifolin Attenuates Dextran Sulfate Sodium-Induced Colitis: Impact on Intestinal Barrier, Intestinal Inflammation and Gut Microbiota

Planta Medica ◽

10.1055/a-1506-3476 ◽

2021 ◽

Author(s):

Jiaqi Wu ◽

Yuzheng Wu ◽

Yue Chen ◽

Mengyang Liu ◽

Haiyang Yu ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Intestinal Inflammation ◽

Activity Index ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Function Evaluation ◽

Biological Drugs

AbstractUlcerative colitis has been recognized as a chronic inflammatory disease predominantly disturbing the colon and rectum. Clinically, the aminosalicylates, steroids, immunosuppressants, and biological drugs are generally used for the treatment of ulcerative colitis at different stages of disease progression. However, the therapeutic efficacy of these drugs does not satisfy the patients due to the frequent drug resistance. Herein, we reported the anti-ulcerative colitis activity of desmethylbellidifolin, a xanthone isolated from Gentianella acuta, in dextran sulfate sodium-induced colitis in mice. C57BL/6 mice were treated with 2% dextran sulfate sodium in drinking water to induce acute colitis. Desmethylbellidifolin or balsalazide sodium was orally administrated once a day. Biological samples were collected for immunohistological analysis, intestinal barrier function evaluation, cytokine measurement, and gut microbiota analysis. The results revealed that desmethylbellidifolin alleviated colon shortening and body weight loss in dextran sulfate sodium-induced mice. The disease activity index was also lowered by desmethylbellidifolin after 9 days of treatment. Furthermore, desmethylbellidifolin remarkably ameliorated colonic inflammation through suppressing the expression of interleukin-6 and tumor necrosis factor-α. The intestinal epithelial barrier was strengthened by desmethylbellidifolin through increasing levels of occludin, ZO-1, and claudins. In addition, desmethylbellidifolin modulated the gut dysbiosis induced by dextran sulfate sodium. These findings suggested that desmethylbellidifolin effectively improved experimental ulcerative colitis, at least partly, through maintaining intestinal barrier integrity, inhibiting proinflammatory cytokines, and modulating dysregulated gut microbiota.

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The serotonin reuptake transporter is reduced in the epithelium of active Crohn’s disease and ulcerative colitis

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00244.2020 ◽

2020 ◽

Vol 319 (6) ◽

pp. G761-G768

Author(s):

Jonas Woll Jørandli ◽

Silje Thorsvik ◽

Helene Kolstad Skovdahl ◽

Benedikt Kornfeld ◽

Siri Sæterstad ◽

...

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Intestinal Epithelium ◽

Serotonin Reuptake ◽

Tryptophan Hydroxylase ◽

Intestinal Inflammation ◽

Serotonin Synthesis ◽

Crohn’S Colitis ◽

Tnf Α ◽

Serotonin Reuptake Transporter

The serotonin reuptake transporter is potently reduced in inflamed areas of Crohn’s ileitis, Crohn’s colitis, and ulcerative colitis. The changes are localized to the intestinal epithelium and can be induced by TNF-α. The serotonin synthesis through tryptophan hydroxylase 1 is unchanged. This regulation is suggested as a mechanism underlying the increased extracellular serotonin levels associated with intestinal inflammation.

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Retinoic Acid Is Elevated in the Mucosa of Patients With Active Ulcerative Colitis and Displays a Proinflammatory Role by Augmenting IL-17 and IFNγ Production

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa121 ◽

2020 ◽

Vol 27 (1) ◽

pp. 74-83 ◽

Cited By ~ 3

Author(s):

Ritika Rampal ◽

Nahidul Wari ◽

Amit Kumar Singh ◽

Ujjwalkumar Das ◽

Sawan Bopanna ◽

...

Keyword(s):

Ulcerative Colitis ◽

T Cells ◽

Retinoic Acid ◽

Crucial Role ◽

Intestinal Inflammation ◽

Γδ T Cells ◽

Inflammatory Conditions ◽

Invariant T Cells ◽

Active Disease

Abstract Background All-trans retinoic acid (RA) plays a crucial role in promoting Foxp3+ Treg generation while reciprocally inhibiting Th1/Th17 generation. Our previous research highlighted that in the face of inflammatory conditions, RA plays a contrary role where it aggravates intestinal inflammation by promoting interferon (IFN) γ and interleukin (IL)-17 differentiation in vitro. Methods In this study we translated our in vitro results into a clinical setting where we estimated mucosal and serum RA levels along with the immunophenotypic profile (IL-17, IFNγ, Foxp3, IL-10) in adaptive (CD4, CD8) and innate-like T cells (mucosal associated invariant T cells and γδ T cells) in patients with ulcerative colitis in remission or with active inflammation. Results This is the first study to estimate RA levels in the human gut and shows that patients with active disease had increased mucosal RA levels as compared with patients in remission (4.0 vs 2.5 ng/mL; P < 0.01) and control patients (3.4 vs 0.8 ng/mL; P < 0.0001). This effect was accompanied by significantly elevated IL-17 and IFNγ in tissue CD4+, CD8+, mucosal associated invariant T+ cells, and γδ + T cells. Moreover, the raised RA levels in patients with active disease showed a positive correlation with proinflammatory cytokines (IL-17, IFNγ) and a negative correlation with IL-10. We also found that RA negatively correlated with IL-9, thereby reinstating our previous finding that RA inhibits Th9 differentiation. Conclusions These data confirm our previous in vitro results that in the presence of inflammation, RA plays a crucial role in maintaining gut inflammation by upregulating proinflammatory markers.

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