• Title/Summary/Keyword: Inflammatory Bowel Disease(IBD)

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Effect of DA-6034, a Derivative of Flavonoid, on Experimental Animal Models of Inflammatory Bowel Disease

  • Kim, You-Sun;Son, Mi-Won;Ko, Jun-Il;Cho, Hyeon;Yoo, Moo-Hi;Kim, Won-Bae;Song, In-Sung;Kim, Chung-Yong
    • Archives of Pharmacal Research
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    • v.22 no.4
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    • pp.354-360
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    • 1999
  • Inflammatory bowel disease (IBD) is a multifactorial disorder with unknown etiology and pathogenesis. DA-6034,$ 7-carboxymethyloxy-3^{l}, 4^{l},$ 5-trimethoxy flavone, is a synthetic flavonoid known to possess anti-inflammatory activity. This study was performed to evaluate the oral therapeutic effect of DA-6034 in three experimental animal models of IBD : two chemical-induced IBD models of rats and the human leukocyte antigen (HLA)-B27 transgenic rat model known to develop spontaneous colitis without the use of exogenous agents. Acute chemical colitis was induced by intracolonic instillation of 1.2 ml of 4% acetic acid solution. Prednisolone (1 mg/kg), sulfasalazine (100 mg/kg) and DA-6034 (0.3~3 mg/kg) were orally administered twice daily for 6 days in these rats. In addition, chronic chemical colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid (TNBS) 30 mg in 50% ethanol and agents were orally administered for 6 or 20 days. In chemical-induced IBD models, all of these agents reduced the severity of colitis and specially, DA-6034 (3 mg/kg) showed more potent effect than other drugs in macroscopic lesion score. In HLA-B27 transgenic rats, DA-6034 (3 mg/kg) and prednisolone (0.5 gm/kg) were treated orally twice daily for 6 weeks. The HLA-B27 transgenic rats showed only mild colitis, compared with the chemical-induced colitis models. DA-6034 ameliorated the loose stool and decreased microscopic damage, which is the important indicator of this model. In conclusion, oral therapy of DA-6034 attenuated the macroscopic and histologic damages of the colon in all three experimental models of IBD, which suggest that DA-6034 could be a promising drug in the treatment of IBD.

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Lactic Acid Bacteria Isolated from Human Breast Milk Improve Colitis Induced by 2,4,6-Trinitrobenzene Sulfonic Acid by Inhibiting NF-κB Signaling in Mice

  • Kyung-Joo Kim;Suhyun Kyung;Hui Jin;Minju Im;Jae-won Kim;Hyun Su Kim;Se-Eun Jang
    • Journal of Microbiology and Biotechnology
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    • v.33 no.8
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    • pp.1057-1065
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    • 2023
  • Inflammatory bowel disease (IBD), a chronic inflammatory disease, results from dysregulation of the immune responses. Some lactic acid bacteria (LAB), including Lactobacillus, alleviate IBD through immunomodulation. In this study, the anti-colitis effect of LAB isolated from human breast milk was investigated in a mouse model induced acute colitis with 2,4,6-trinitrobenzene sulfonic acid (TNBS). TNBS remarkably increased weight loss, colon shortening, and colonic mucosal proliferation, as well as the expression levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1β. Oral administration of LAB isolated from human breast milk resulted in a reduction in TNBS-induced colon shortening, as well as induced cyclooxygenase (COX)-2, nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB). In addition, LAB suppressed inflammatory cytokines such as TNF-α, IL-6, and IL-1β, and thus showed an effect of suppressing the level of inflammation induced by TNBS. Furthermore, LAB alleviated gut microbiota dysbiosis, and inhibited intestinal permeability by increasing the expression of intestinal tight junction protein including ZO-1. Collectively, these results suggest that LAB isolated from human breast milk can be used as a functional food for colitis treatment by regulating NF-κB signaling, gut microbiota and increasing expression of intestinal tight junction protein.

From Gut to Brain: Alteration in Inflammation Markers in the Brain of Dextran Sodium Sulfate-induced Colitis Model Mice

  • Do, Jongho;Woo, Jungmin
    • Clinical Psychopharmacology and Neuroscience
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    • v.16 no.4
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    • pp.422-433
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    • 2018
  • Objective: Neuropsychiatric manifestations like depression and cognitive dysfunction commonly occur in inflammatory bowel disease (IBD). In the context of the brain-gut axis model, colitis can lead to alteration of brain function in a bottom-up manner. Here, the changes in the response of the hypothalamic-pituitary-adrenal axis and inflammation-related markers in the brain in colitis were studied. Methods: Dextran sodium sulfate (DSS) was used to generate a mouse model of colitis. Mice were treated with DSS for 3 or 7 days and sacrificed. We analyzed the gene expression of brain-derived neurotrophic factor (BDNF), cyclooxygenase 2 (COX-2), and glial fibrillary acidic protein (GFAP), and the expression of GFAP, in the hippocampus, hypothalamus, and amygdala. Additionally, the levels of C-reactive protein (CRP) and serum cortisol/corticosterone were measured. Results: Alteration of inflammatory-related markers varied depending on the brain region and exposure time. In the hippocampus, COX-2 mRNA, GFAP mRNA, and GFAP expression were upregulated during exposure to DSS. However, in the hypothalamus, COX-2 mRNA was upregulated only 3 days after treatment. In the amygdala, BDNF and COX-2 mRNAs were downregulated. CRP and corticosterone expression increased with DSS treatment at day 7. Conclusion: IBD could lead to neuroinflammation in a bottom-up manner, and this effect varied according to brain region. Stress-related hormones and serum inflammatory markers, such as CRP, were upregulated from the third day of DSS treatment. Therefore, early and active intervention is required to prevent psychological and behavioral changes caused by IBD, and region-specific studies can help understand the precise mechanisms by which IBD affects the brain.

Leaky Gut in IBD: Intestinal Barrier-Gut Microbiota Interaction

  • Yu, Shunying;Sun, Yibin;Shao, Xinyu;Zhou, Yuqing;Yu, Yang;Kuai, Xiaoyi;Zhou, Chunli
    • Journal of Microbiology and Biotechnology
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    • v.32 no.7
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    • pp.825-834
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    • 2022
  • Inflammatory bowel disease (IBD) is a global disease that is in increasing incidence. The gut, which contains the largest amount of lymphoid tissue in the human body, as well as a wide range of nervous system components, is integral in ensuring intestinal homeostasis and function. By interacting with gut microbiota, immune cells, and the enteric nervous system, the intestinal barrier, which is a solid barrier, protects the intestinal tract from the external environment, thereby maintaining homeostasis throughout the body. Destruction of the intestinal barrier is referred to as developing a "leaky gut," which causes a series of changes relating to the occurrence of IBD. Changes in the interactions between the intestinal barrier and gut microbiota are particularly crucial in the development of IBD. Exploring the leaky gut and its interaction with the gut microbiota, immune cells, and the neuroimmune system may help further explain the pathogenesis of IBD and provide potential therapeutic methods for future use.

Immunofluorescence Microscopic Evaluation of Tight Junctional Proteins during Enterotoxigenic Bacteroides fragilis (ETBF) Infection in Mice

  • Hwang, Soonjae;Kang, Yeowool;Jo, Minjeong;Kim, Sung Hoon;Cho, Won Gil;Rhee, Ki-Jong
    • Biomedical Science Letters
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    • v.24 no.3
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    • pp.275-279
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    • 2018
  • Inflammatory bowel disease (IBD) is increasing in prevalence in developed countries but the cause of this increase is unclear. In animal models of IBD and in human IBD patients, alterations in the tight junctional proteins have been observed, suggesting that the intestinal microflora may penetrate the underlying colonic tissue and promote inflammation. Enterotoxigenic Bacteroides fragilis (ETBF) causes inflammatory diarrhea in human and is implicated in inflammatory bowel diseases. However, it is unclear whether alterations in tight junctional proteins occur during ETBF infection in mice. In this brief communication, we report that ETBF infection induces up-regulation of claudin-2 and down-regulation of claudin-5 through B. fragilis toxin (BFT) activity in the large intestine of C57BL/6 mice. In contrast, BFT did not induce changes in tight junctional proteins in the HT29/C1 cell line, suggesting that analysis of biological activity of BFT in vivo is important for evaluating ETBF effects.

Pediatric Inflammatory Bowel Disease: A Multicenter Study of Changing Trends in Argentina Over the Past 30 Years

  • Arcucci, Maria Soledad;Contreras, Monica Beatriz;Gallo, Julieta;Antoniska, Mariela Andrea;Busoni, Veronica;Tennina, Cecilia;D’Agostino, Daniel;Kakisu, Maria Hisae;Weyersberg, Christian;Orsi, Marina
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.25 no.3
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    • pp.218-227
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    • 2022
  • Purpose: To analyze the characteristics of pediatric inflammatory bowel disease (IBD) over the past three decades in Argentina and determine if there are differences between the first two decades and the past decade. Methods: We conducted a retrospective multicenter analytical study in children with IBD between 0 and 18 years of age diagnosed between 1987 and 2017 in three tertiary health centers in Argentina. The evaluation included clinical characterization, endoscopy, histology, and imaging data together with therapeutic strategies. The patients were divided into two groups: Group 1, diagnosed between 1987 and 2007, and Group 2, diagnosed between 2008 and 2017. Results: Of the 756 patients included, 409 (54%) had ulcerative colitis (UC), 250 (33%) had Crohn's disease (CD), and 97 (13%) had IBD-unclassified (IBD-U). The positive family history was 3.8%, which was more frequent among children under two years of age (6.7%). There were no significant differences in clinical presentation and extraintestinal manifestations between periods, with hepatic manifestations being the most frequent. In the last decade, we found an upward trend in CD, a downward trend in UC/IBD-U, even after adjustment for socioeconomic status, and a decrease of 50% in surgical treatments coinciding with the advent of biological therapy. Conclusion: This is the first multicenter cohort study in a Latin American country to describe clinical, endoscopic, and therapeutic data across the past 30-year period. Although CD was responsible for the overall increase in incidence, UC was still prevalent in this region.

Efficacy and safety of endoscopic submucosal dissection for colorectal dysplasia in patients with inflammatory bowel disease: a systematic review and meta-analysis

  • Talia F. Malik;Vaishnavi Sabesan;Babu P. Mohan;Asad Ur Rahman;Mohamed O. Othman;Peter V. Draganov;Gursimran S. Kochhar
    • Clinical Endoscopy
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    • v.57 no.3
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    • pp.317-328
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    • 2024
  • Background/Aims: In this meta-analysis, we studied the safety and efficacy of endoscopic submucosal dissection (ESD) for colorectal dysplasia in patients with inflammatory bowel disease (IBD). Methods: Multiple databases were searched, and studies were retrieved based on pre-specified criteria until October 2022. The outcomes assessed were resection rates, procedural complications, local recurrence, metachronous tumors, and the need for surgery after ESD in IBD. Standard meta-analysis methods were followed using the random-effects model, and I2% was used to assess heterogeneity. Results: Twelve studies comprising 291 dysplastic lesions in 274 patients were included with a median follow-up of 25 months. The pooled en-bloc resection, R0 resection, and curative resection rates were 92.5% (95% confidence interval [CI], 87.9%-95.4%; I2=0%), 81.5% (95% CI, 72.5%-88%; I2=43%), and 48.9% (95% CI, 32.1%-65.9%; I2=87%), respectively. The local recurrence rate was 3.9% (95% CI, 2%-7.5%; I2=0%). The pooled rates of bleeding and perforation were 7.7% (95% CI, 4.5%-13%; I2=10%) and 5.3% (95% CI, 3.1%-8.9%; I2=0%), respectively. The rates of metachronous recurrence and additional surgery following ESD were 10% (95% CI, 5.2%-18.2%; I2=55%) and 13% (95% CI, 8.5%-19.3%; I2=54%), respectively. Conclusions: ESD is safe and effective for the resection of dysplastic lesions in IBD with an excellent pooled rate of en-bloc and R0 resection.

Prevalence of Inflammatory Bowel Disease Unclassified, as Estimated Using the Revised Porto Criteria, among Korean Pediatric Patients with Inflammatory Bowel Disease

  • Sung Hee Lee;Minsoo Shin;Seo Hee Kim;Seong Pyo Kim;Hyung-Jin Yoon;Yangsoon Park;Jaemoon Koh;Seak Hee Oh;Jae Sung Ko;Jin Soo Moon;Kyung Mo Kim
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.27 no.4
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    • pp.206-214
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    • 2024
  • Purpose: Few studies have reported the prevalence of inflammatory bowel disease unclassified (IBDU) among Korean pediatric IBD (PIBD) population. To address this gap, we used two tertiary centers and nationwide population-based healthcare administrative data to estimate the prevalence of Korean pediatric IBDU at the time of diagnosis. Methods: We identified 136 patients aged 2-17 years with newly diagnosed IBD (94 Crohn's disease [CD] and 42 ulcerative colitis [UC]) from two tertiary centers in Korea between 2005 and 2017. We reclassified these 136 patients using the revised Porto criteria. To estimate the population-based prevalence, we analyzed Korean administrative healthcare data between 2005 and 2016, which revealed 3,650 IBD patients, including 2,538 CD and 1,112 UC. By extrapolating the reclassified results to a population-based dataset, we estimated the prevalence of PIBD subtypes. Results: Among the 94 CD, the original diagnosis remained unchanged in 93 (98.9%), while the diagnosis of one (1.1%) patient was changed to IBDU. Among the 42 UC, the original diagnosis remained unchanged in 13 (31.0%), while the diagnoses in 11 (26.2%), 17 (40.5%), and one (2.4%) patient changed to atypical UC, IBDU, and CD, respectively. The estimated prevalences of CD, UC, atypical UC, and IBDU in the Korean population were 69.5%, 9.4%, 8.0%, and 13.1%, respectively. Conclusion: This study is the first in Korea to estimate the prevalence of pediatric IBDU. This prevalence (13.1%) aligns with findings from Western studies. Large-scale prospective multicenter studies on PIBDU are required to examine the clinical features and outcomes of this condition.

Context-Dependent Regulation of Type17 Immunity by Microbiota at the Intestinal Barrier

  • Begum Akuzum;June-Yong Lee
    • IMMUNE NETWORK
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    • v.22 no.6
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    • pp.46.1-46.25
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    • 2022
  • T-helper-17 (Th17) cells and related IL-17-producing (type17) lymphocytes are abundant at the epithelial barrier. In response to bacterial and fungal infection, the signature cytokines IL-17A/F and IL-22 mediate the antimicrobial immune response and contribute to wound healing of injured tissues. Despite their protective function, type17 lymphocytes are also responsible for various chronic inflammatory disorders, including inflammatory bowel disease (IBD) and colitis associated cancer (CAC). A deeper understanding of type17 regulatory mechanisms could ultimately lead to the discovery of therapeutic strategies for the treatment of chronic inflammatory disorders and the prevention of cancer. In this review, we discuss the current understanding of the development and function of type17 immune cells at the intestinal barrier, focusing on the impact of microbiota-immune interactions on intestinal barrier homeostasis and disease etiology.

Seaweed Derived Oligosaccharides and its Health Beneficial Effects on Gut Health (해조류 유래 다당류와 장 건강)

  • Yang, Hyosun;Lee, Yunkyoung
    • The Journal of the Korea Contents Association
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    • v.16 no.7
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    • pp.465-475
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    • 2016
  • The incidence of inflammatory bowel disease(IBD) has increased continuously in worldwide, but no cure have been discovered. The etiology of IBD may include various factors such as genetics, epigenetic, environment as well as host immune system. Among the environmental factors of IBD, diet heavily influences gut health, especially non-digestible dietary fiber can have a great impact on selective growth of beneficial gut microbiota called probiotics. Seaweeds have been consumed in Asia countries and are a rich source for dietary fiber. Accumulated data have suggested the possibility of utilizing seaweed derived oligosaccharides as prebiotics to prevent IBD and its recurrence. In this review, seaweed derived oligosaccharides such as fucoidan and laminarin regarding gut health and potential therapeutic tools for IBD will be discussed based on studies conducted in vitro and in vivo models.