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Colitis mice

Nijiati Abulizi, Candice Quin, Kirsty Brown, Yee Kwan Chan, Sandeep K Gill, Deanna L Gibson
The dynamics of the tripartite relationship between the host, gut bacteria and diet in the gut is relatively unknown. An imbalance between harmful and protective gut bacteria, termed dysbiosis, has been linked to many diseases and has most often been attributed to high-fat dietary intake. However, we recently clarified that the type of fat, not calories, were important in the development of murine colitis. To further understand the host-microbe dynamic in response to dietary lipids, we fed mice isocaloric high-fat diets containing either milk fat, corn oil or olive oil and performed 16S rRNA gene sequencing of the colon microbiome and mass spectrometry-based relative quantification of the colonic metaproteome...
February 16, 2019: Nutrients
Cao Jin, Cheng Jin, Xi Siyu, Qi Xueyong, Shen Song, Ge Yanru
Targeted delivery of bioactive compounds such as proteins to the colon has numerous advantages for the therapeutic treatment of inflammatory bowel disease. The present study sought to fabricate alginate/chitosan microcapsules containing IL-1Ra (Alg/Chi/IL-1Ra MC) via a single-step electrospraying method. Two important factors of efficacy were measured-the pH-responsiveness of the microcapsule and the in-vitro drug release profile. The DSS-induced colitis mouse model was used to evaluate the therapeutic effect of the Alg/Chi/IL-1Ra microcapsules, with results showing the protective effect of the Alg/Chi microcapsules for the passage of IL-1Ra through the harsh environment of the upper gastrointestinal tract...
February 16, 2019: European Journal of Pharmaceutics and Biopharmaceutics
Yuhua Tian, Jiuzhi Xu, Yuan Li, Ran Zhao, Sujuan Du, Cong Lv, Wei Wu, Ruiqi Liu, Xiaole Sheng, Yongli Song, Xueyun Bi, Guilin Li, Mengzhen Li, Xi Wu, Pengbo Lou, Huiwen You, Wei Cui, Jinyue Sun, Jianwei Shuai, Fazheng Ren, Bing Zhang, Mingzhou Guo, Xiaohua Hou, Kaichun Wu, Lixiang Xue, Hongquan Zhang, Maksim V Plikus, Yingzi Cong, Christopher J Lengner, Zhanju Liu, Zhengquan Yu
BACKGROUND & AIMS: Levels of microRNA 31 (MIR31) are increased in intestinal tissues from patients with inflammatory bowel diseases and colitis-associated neoplasias. We investigated the effects of this microRNA on intestinal inflammation by studying mice with colitis. METHODS: We obtained colon biopsy samples from 82 patients with ulcerative colitis (UC), 79 patients with Crohn's disease (CD), and 34 healthy individuals (controls) at Shanghai Tenth People's Hospital...
February 16, 2019: Gastroenterology
Yang Wang, Toshimitsu Hatabu
This study aimed to evaluate the microbial compositions and gene expression related to inflammation in dextran sodium sulfate (DSS)-induced acute colitis and the effect of mulberry supplementation. Male BALB/c mice received a diet supplemented with mulberry juice freeze-dried powder (MFP) or not for 3 weeks. After 3 weeks, the mice received water containing 5% (w/v) DSS or not for 1 week. The disease activity index score in mice fed MFP was significantly decreased. A significant decrease in Bifidobacterium spp...
February 17, 2019: Bioscience, Biotechnology, and Biochemistry
Zi Wang, Soichiro Adachi, Lingling Kong, Daisuke Watanabe, Yusuke Nakanishi, Toshiaki Ohteki, Namiko Hoshi, Yuzo Kodama
Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD), which is triggered spontaneously by unknown mechanisms and manifests as chronic and relapsing inflammatory conditions in the colon. Eosinophil infiltration is often observed in the colonic tissue of ulcerative colitis patients. However, the role of eosinophils in the disease has not been well defined. The aim of this study is to investigate the role of eosinophils in colonic inflammation using the murine model of spontaneous colitis. CC chemokine receptor type 3 (CCR3) and interleukin (IL)-10 double knockout mice (CCR3-/-;IL-10-/-) were utilized to evaluate the function of eosinophils in colitis...
February 13, 2019: Biochemical and Biophysical Research Communications
Yan-Hong Li, Wei Sun, Bao-Jin Zhou, Adam Rosenstein, Jie Zhao, Jian Wang, Zhao-Xiang Bian
Previous studies by us and others have indicated that berberine is a promising therapy for ulcerative colitis (UC). However, the mechanisms of UC and the therapeutic targets of berberine are poorly understood. iTRAQ-based proteomics was utilized to characterize the proteins and pathways associated with the development of colitis and its improvement after berberine treatment. By using a dextran sodium sulfate (DSS) colitis as the UC model, we demonstrated that berberine significantly attenuated clinical symptoms and colon shorting of the colitis mice...
February 13, 2019: European Journal of Pharmacology
Maik Luu, Sabine Pautz, Vanessa Kohl, Rajeev Singh, Rossana Romero, Sébastien Lucas, Jörg Hofmann, Hartmann Raifer, Niyati Vachharajani, Lucia Campos Carrascosa, Boris Lamp, Andrea Nist, Thorsten Stiewe, Yoav Shaul, Till Adhikary, Mario M Zaiss, Matthias Lauth, Ulrich Steinhoff, Alexander Visekruna
Short-chain fatty acids (SCFAs) have immunomodulatory effects, but the underlying mechanisms are not well understood. Here we show that pentanoate, a physiologically abundant SCFA, is a potent regulator of immunometabolism. Pentanoate induces IL-10 production in lymphocytes by reprogramming their metabolic activity towards elevated glucose oxidation. Mechanistically, this reprogramming is mediated by supplying additional pentanoate-originated acetyl-CoA for histone acetyltransferases, and by pentanoate-triggered enhancement of mTOR activity...
February 15, 2019: Nature Communications
Federica Laudisi, Davide Di Fusco, Vincenzo Dinallo, Carmine Stolfi, Antonio Di Grazia, Irene Marafini, Alfredo Colantoni, Angela Ortenzi, Claudia Alteri, Francesca Guerrieri, Maria Mavilio, Francesca Ceccherini-Silberstein, Massimo Federici, Thomas Thornton MacDonald, Ivan Monteleone, Giovanni Monteleone
BACKGROUND & AIMS: Food additives, such as emulsifiers, stabilizers, or bulking agents, are present in the Western diet and their consumption is increasing. However, little is known about their potential effects on intestinal homeostasis. In this study we examined the effect of some of these food additives on gut inflammation. METHODS: Mice were given drinking water containing maltodextrin (MDX), propylene glycol, or animal gelatin, and then challenged with dextran sulfate sodium or indomethacin...
September 11, 2018: Cellular and Molecular Gastroenterology and Hepatology
Lasha Gogokhia, Kate Buhrke, Rickesha Bell, Brenden Hoffman, D Garrett Brown, Christin Hanke-Gogokhia, Nadim J Ajami, Matthew C Wong, Arevik Ghazaryan, John F Valentine, Nathan Porter, Eric Martens, Ryan O'Connell, Vinita Jacob, Ellen Scherl, Carl Crawford, W Zac Stephens, Sherwood R Casjens, Randy S Longman, June L Round
Bacteriophages are the most abundant members of the microbiota and have the potential to shape gut bacterial communities. Changes to bacteriophage composition are associated with disease, but how phages impact mammalian health remains unclear. We noted an induction of host immunity when experimentally treating bacterially driven cancer, leading us to test whether bacteriophages alter immune responses. Treating germ-free mice with bacteriophages leads to immune cell expansion in the gut. Lactobacillus, Escherichia, and Bacteroides bacteriophages and phage DNA stimulated IFN-γ via the nucleotide-sensing receptor TLR9...
February 13, 2019: Cell Host & Microbe
Andrew Leber, Raquel Hontecillas, Victoria Zoccoli-Rodriguez, Jyoti Chauhan, Josep Bassaganya-Riera
Inflammatory bowel disease (IBD) is an expanding autoimmune disease afflicting millions that remains difficult to treat due to the accumulation of multiple immunological changes. BT-11 is an investigational new drug for IBD that is orally active, gut restricted, and targets the lanthionine synthetase C-like 2 immunometabolic pathway. CD25+ FOXP3+ CD4+ T cells are increased locally within the colon of BT-11-treated mice in Citrobacter rodentium and IL-10-/- mouse models of colitis. The maintained efficacy of BT-11 in the absence of IL-10 combined with the loss of efficacy when direct cell-cell interactions are prevented suggest that the regulatory T cell (Treg)-related elements of suppression are cell contact-mediated...
February 13, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
Peter Allan Dobranowski, Chris Tang, Jean Philippe Sauvé, Susan Christine Menzies, Laura May Sly
Inflammatory bowel disease, encompassing both ulcerative colitis and Crohn's disease, is characterized by chronic, relapsing-remitting gastrointestinal inflammation of unknown etiology. SHIP deficient mice develop fully penetrant, spontaneous ileitis at 6 weeks of age, and thus offer a tractable model of Crohn's disease-like inflammation. Since disruptions to the microbiome are implicated in the pathogenesis of Crohn's disease, we conducted a 16S rRNA gene survey of the ileum, cecum, colon, and stool contents of SHIP+/+ and SHIP-/- mice...
February 13, 2019: Gut Microbes
Veronica M Ringel-Scaia, Yufeng Qin, Cassidy A Thomas, Kathleen E Huie, Dylan K McDaniel, Kristin Eden, Paul A Wade, Irving C Allen
The NLRP1 inflammasome attenuates inflammatory bowel disease (IBD) progression and colitis-associated tumorigenesis. A possible mechanism postulates that the lack of the NLRP1 inflammasome creates permissive niches in the gut for pathogenic bacteria to flourish, causing dysbiosis and increased IBD susceptibility. To evaluate this hypothesis, we characterized the gut microbiome of wild-type, Nlrp1b-/-, and Asc-/- mice under naïve conditions by sequencing the V3 region of the 16s rRNA gene. For both genetically modified mouse lines, the microbiome composition reflected overrepresentation of bacteria associated with dysbiosis relative to wild-type animals...
February 13, 2019: Journal of Innate Immunity
Hisako Kayama, Haruka Tani, Shoko Kitada, Anunya Opasawatchai, Ryu Okumura, Daisuke Motooka, Shota Nakamura, Kiyoshi Takeda
Inappropriate activation of the interleukin (IL)-23 signaling pathway causes chronic inflammation through the induction of immunopathological Th17 cells in several tissues including the intestine, whereas adequate Th17 responses are essential for host defense against harmful organisms. In the intestinal lamina propria, IL-23 is primarily produced by innate myeloid cells including dendritic cells (DCs) and macrophages (Ms). However, the molecular mechanisms underlying the regulation of IL-23 production by these cells remains poorly understood...
February 12, 2019: International Immunology
Anders B Nexoe, Bartosz Pilecki, Sebastian Von Huth, Steffen Husby, Andreas A Pedersen, Sönke Detlefsen, Niels Marcussen, Jesper B Moeller, Uffe Holmskov, Grith L Sorensen
Background: Inflammatory bowel diseases (IBD) are chronic disorders of the gastrointestinal tract. Surfactant protein D (SP-D) is expressed in the intestinal epithelium and is essential for innate host defense and regulation of inflammatory responses. Genetic variations of SP-D are associated with IBD, but the effects of SP-D in clinical disease development have not been clarified. We hypothesized that colonic epithelial SP-D expression is increased in parallel with intestinal inflammation with the capacity to dampen deleterious effects...
February 8, 2019: Inflammatory Bowel Diseases
Weiwei Li, Xinhua Zhao, Xue Lv, Wenxiao Han, Hongying Wang
Purpose: Silibinin possesses the efficacy of anticancer and anti-inflammation. We aimed to test whether silibinin could prevent colitis-associated carcinogenesis in mouse model. Experimental Design: Azoxymethane (AOM) and dextran sulfate sodium (DSS) were used to induce colitis-associated tumorigenesis in C57BL mice. Six-to-eight-week-old male mice were gavaged with 350 or 750 mg/kg of silibinin for 10 weeks right after DSS administration. The mice were then sacrificed, and colon tissues were measured for tumor multiplicity and size...
February 11, 2019: Inflammatory Bowel Diseases
Annika Wyss, Tina Raselli, Nathan Perkins, Florian Ruiz, Gérard Schmelczer, Glynis Klinke, Anja Moncsek, René Roth, Marianne R Spalinger, Larissa Hering, Kirstin Atrott, Silvia Lang, Isabelle Frey-Wagner, Joachim C Mertens, Michael Scharl, Andreas W Sailer, Oliver Pabst, Martin Hersberger, Caroline Pot, Gerhard Rogler, Benjamin Misselwitz
The gene encoding for Epstein-Barr virus-induced G-protein-coupled receptor 2 (EBI2) is a risk gene for inflammatory bowel disease (IBD). Together with its oxysterol ligand 7α,25-dihydroxycholesterol, EBI2 mediates migration and differentiation of immune cells. However, the role of EBI2 in the colonic immune system remains insufficiently studied. We found increased mRNA expression of EBI2 and oxysterol-synthesizing enzymes (CH25H, CYP7B1) in the inflamed colon of patients with ulcerative colitis and mice with acute or chronic dextran sulfate sodium (DSS) colitis...
February 11, 2019: Mucosal Immunology
Jin Imai, Sho Kitamoto, Kohei Sugihara, Hiroko Nagao-Kitamoto, Atsushi Hayashi, Tina L Morhardt, Peter Kuffa, Peter D R Higgins, Nicolas Barnich, Nobuhiko Kamada
Intestinal fibrosis is a severe complication in patients with Crohn's disease (CD). Unfortunately, the trigger leading to the development of intestinal fibrosis in the context of CD remains elusive. Here, we show that colonization by a CD-associated pathobiont adherent-invasive Escherichia coli (AIEC) promotes the development of intestinal fibrosis. Exogenously inoculated AIEC strain LF82 and commensal E. coli HS were gradually eradicated from the intestine in healthy mice. In Salmonella- or dextran sodium sulfate-induced colitis models, AIEC exploited inflammation and stably colonize the gut...
February 11, 2019: Mucosal Immunology
Jie Zhang, Di Qin, Yong-Jun Yang, Gui-Qiu Hu, Xiao-Xia Qin, Chong-Tao Du, Wei Chen
The maintenance of intestinal tissue homeostasis is vital for the resistance against inflammatory bowel diseases (IBDs). Necroptosis is identified as an alternative mode of regulated cell death, which plays a pivotal role in tissue homeostasis. Thus, the roles of RIP3-mediated necroptosis in intestinal inflammation have been extensively studied. However, the biological implications of the mixed lineage kinase-like protein (MLKL), a molecule downstream of RIP3 in gut remain unclear. In this study, the role of MLKL in DSS-induced colitis was examined, and the contribution of gut microbiota was also determined...
February 6, 2019: Molecular Immunology
Marta M Wegorzewska, Robert W P Glowacki, Samantha A Hsieh, David L Donermeyer, Christina A Hickey, Stephen C Horvath, Eric C Martens, Thaddeus S Stappenbeck, Paul M Allen
T cell responses to symbionts in the intestine drive tolerance or inflammation depending on the genetic background of the host. These symbionts in the gut sense the available nutrients and adapt their metabolic programs to use these nutrients efficiently. Here, we ask whether diet can alter the expression of a bacterial antigen to modulate adaptive immune responses. We generated a CD4+ T cell hybridoma, BθOM, specific for Bacteroides thetaiotaomicron ( B. theta ). Adoptively transferred transgenic T cells expressing the BθOM TCR proliferated in the colon, colon-draining lymph node, and spleen in B...
February 8, 2019: Science Immunology
Laëtitia Kermarrec, Nour Eissa, Hongxing Wang, Kunal Kapoor, Abdoulaye Diarra, Abdelilah S Gounni, Charles N Bernstein, Jean-Eric Ghia
BACKGROUND AND PURPOSE: Alteration of the communication between the innate and adaptive immune cells is a hallmark of ulcerative colitis (UC). Semaphorin-3E (SEMA3E), a secreted guidance protein, regulates various immune responses. EXPERIMENTAL APPROACH: We investigated SEMA3E expression in colonic biopsies of active UC patients and its mechanisms in Sema3e-/- mice using a UC model of experimental colitis. KEY-RESULTS: SEMA3E level was decreased in active UC patients and negatively correlated with pro-inflammatory mediators...
February 8, 2019: British Journal of Pharmacology
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