Longitudinal Microbiome Analysis in a Dextran Sulfate Sodium-Induced Colitis Mouse Model

The role of the gut microbiota in the pathogenesis of inflammatory bowel disease (IBD) has been in focus for decades. Although metagenomic observations in patients/animal colitis models have been attempted, the microbiome results were still indefinite and broad taxonomic presumptions were made due to the cross-sectional studies. Herein, we conducted a longitudinal microbiome analysis in a dextran sulfate sodium (DSS)-induced colitis mouse model with a two-factor design based on serial DSS dose (0, 1, 2, and 3%) and duration for 12 days, and four mice from each group were sacrificed at two-day intervals. During the colitis development, a transition of the cecal microbial diversity from the normal state to dysbiosis and dynamic changes of the populations were observed. We identified genera that significantly induced or depleted depending on DSS exposure, and confirmed the correlations of the individual taxa to the colitis severity indicated by inflammatory biomarkers (intestinal bleeding and neutrophil-derived indicators). Of note, each taxonomic population showed its own susceptibility to the changing colitis status. Our findings suggest that an understanding of the individual susceptibility to colitis conditions may contribute to identifying the role of the gut microbes in the pathogenesis of IBD.

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The role of the complement and contact systems in the dextran sulfate sodium-induced colitis model: the effect of C1 inhibitor in inflammatory bowel disease

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00400.2009 ◽

2010 ◽

Vol 298 (6) ◽

pp. G878-G883 ◽

Cited By ~ 22

Author(s):

Fengxin Lu ◽

Stacey M. Fernandes ◽

Alvin E. Davis

Keyword(s):

Inflammatory Bowel Disease ◽

Weight Loss ◽

Bowel Disease ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Activity Index ◽

Complement C3 ◽

C1 Inhibitor ◽

Inflammatory Bowel

The complement and contact systems may be involved in the pathophysiological process of inflammatory bowel disease (IBD). C1 inhibitor (C1INH) is the most important inhibitor of both the complement and contact systems. We evaluated the role of these systems and the effect of both active and inactive forms of C1INH (iC1INH) in dextran sulfate sodium (DSS)-induced colitis mouse model. Three percent DSS was used in drinking water to induce colitis in complement C3-deficient (C3−/−) mice, bradykinin type 2 receptor deficient (Bk2R−/−) mice, and C57BL/6 mice. After ten days DSS exposure, C3−/− mice exhibited markedly less weight loss than wild-type (WT) mice (12 ± 3.3% vs. 30 ± 1.2%, P < 0.05) and developed a milder disease-activity index (DAI), histological score, colon shortening, and myeloperoxidase (MPO) elevation ( P < 0.05, respectively). The Bk2R−/− mice were not protected from the disease. Seven-day treatment with either native C1INH or iC1INH reduced the severity of the disease in WT mice, as indicated by decreased weight loss (15 ± 1.8%, 14 ± 2.1% vs. 30 ± 1.2%, P < 0.05, respectively), DAI, intestinal tissue damage, and MPO elevation compared with untreated WT DSS control mice ( P < 0.05, respectively). These findings suggest that complement plays a role in the development of DSS-induced colitis and that blockade of the complement system might be useful for the acute phase of IBD treatment. C1INH, however, leads to an amelioration of DSS-induced colitis via a mechanism that does not involve the inhibition of complement or contact system activation but does result in significant suppression of leukocyte infiltration.

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Dextran sulfate sodium mouse model of inflammatory bowel disease evaluated for systemic genotoxicity via blood micronucleus and Pig-a gene mutation assays

Mutagenesis ◽

10.1093/mutage/geaa006 ◽

2020 ◽

Vol 35 (2) ◽

pp. 161-167

Author(s):

Christopher Kirby ◽

Ayesha Baig ◽

Svetlana L Avlasevich ◽

Dorothea K Torous ◽

Shuchang Tian ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Mouse Model ◽

Bowel Disease ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

High Dose ◽

Significant Treatment ◽

Blood Samples ◽

Inflammatory Bowel ◽

Blood Specimens

Abstract Inflammatory bowel disease (IBD) is an important risk factor for gastrointestinal cancers. Inflammation and other carcinogenesis-related effects at distal, tissue-specific sites require further study. In order to better understand if systemic genotoxicity is associated with IBD, we exposed mice to dextran sulfate sodium salt (DSS) and measured the incidence of micronucleated cells (MN) and Pig-a mutant phenotype cells in blood erythrocyte populations. In one study, 8-week-old male CD-1 mice were exposed to 0, 1, 2, 3 or 4% w/v DSS in drinking water. The 4-week in-life period was divided into four 1-week intervals—alternately on then off DSS treatment. Low volume blood samples were collected for MN analysis at the end of each week, and cardiac blood samples were collected at the end of the 4-week period for Pig-a analyses. The two highest doses of DSS were observed to induce significant increases in reticulocyte frequencies. Even so, no statistically significant treatment-related effects on the genotoxicity biomarkers were evident. While one high-dose mouse showed modestly elevated MN frequencies during the DSS treatment cycles, it also exhibited exceptionally high reticulocyte frequencies (e.g. 18.7% at the end of the second DSS cycle). In a second study, mice were treated with 0 or 4% DSS for 9–18 consecutive days. Exposure was continued until rectal bleeding or morbidity was evident, at which point the treatment was terminated and blood was collected for MN analysis. The Pig-a assay was conducted on samples collected 29 days after the start of treatment. The initial blood specimens showed highly elevated reticulocyte frequencies in DSS-exposed mice (mean ± SEM = 1.75 ± 0.10% vs. 13.04 ± 3.66% for 0 vs. 4% mice, respectively). Statistical analyses showed no treatment-related effect on MN or Pig-a mutant frequencies. Even so, the incidence of MN versus reticulocytes in the DSS-exposed mice were positively correlated (linear fit R2 = 0.657, P = 0.0044). Collectively, these results suggest that in the case of the DSS CD-1 mouse model, systemic effects include stress erythropoiesis but not remarkable genotoxicity. To the extent MN may have been slightly elevated in a minority of individual mice, these effects appear to be secondary, likely attributable to stimulated erythropoiesis.

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The Role of Zinc and Metallothionein in the Dextran Sulfate Sodium-Induced Colitis Mouse Model

Digestive Diseases and Sciences ◽

10.1007/s10620-007-9765-9 ◽

2007 ◽

Vol 52 (9) ◽

pp. 2113-2121 ◽

Cited By ~ 43

Author(s):

C. D. Tran ◽

J. M. Ball ◽

S. Sundar ◽

P. Coyle ◽

G. S. Howarth

Keyword(s):

Mouse Model ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium

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The role of mutant Apc in the development of dysplasia and cancer in the mouse model of dextran sulfate sodium–induced colitis

Gastroenterology ◽

10.1053/gast.2001.29609 ◽

2001 ◽

Vol 121 (6) ◽

pp. 1407-1416 ◽

Cited By ~ 66

Author(s):

Harry S. Cooper ◽

Lynette Everley ◽

Wen–Chi Chang ◽

Gordon Pfeiffer ◽

Bryan Lee ◽

...

Keyword(s):

Mouse Model ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium

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Fusobacterium nucleatum impedes remission of colitis in a mouse model

Bioscience Biotechnology and Biochemistry ◽

10.1093/bbb/zbab029 ◽

2021 ◽

Vol 85 (5) ◽

pp. 1235-1242

Author(s):

Taiga Yamashita ◽

Shoya Tai ◽

Takamitsu Tsukahara ◽

Ryo Inoue

Keyword(s):

Drinking Water ◽

Mouse Model ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Fusobacterium Nucleatum ◽

Recovery Phase ◽

Phosphate Buffered Saline ◽

Cecal Mucosa ◽

Activity Indices

ABSTRACT The role of Fusobacterium nucleatum, often associated with intestinal diseases, in the remission of dextran sulfate sodium (DSS)-induced colitis was investigated. Female mice were divided into groups DC (DSS control) and DF (DSS + F. nucleatum). F. nucleatum (1.0 × 1010 cfu/mouse/day) in phosphate-buffered saline (PBS) was orally given to DF, while DC had PBS only. All mice had DSS in drinking water. In Experiment 1, mice underwent 2 inflammation phases, an in-between recovery phase and had their disease activity indices (DAI) calculated. Experiment 2 was similarly conducted, except that mice were dissected 3 days postrecovery, and had blood and colonic mucosal samples collected. In Experiment 1, DF had significantly (P < .05) higher DAI than DC, during the recovery and 2nd inflammation phases. In Experiment 2, genus Bacteroides was significantly (P < .05) higher and family Lachnospiraceae significantly lower in cecal mucosa-associated microbiota of DF than in that of DC. We concluded that F. nucleatum can impede colitis remission.

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Protective and restorative effects of sophorolipid on intestinal dystrophy in dextran sulfate sodium-induced colitis mouse model

Food & Function ◽

10.1039/d1fo03109k ◽

2021 ◽

Author(s):

Min-Jin Kwak ◽

Dong-Jin Ha ◽

Yong-Soon Choi ◽

Hanbae Lee ◽

Kwang-Youn Whang

Keyword(s):

Inflammatory Bowel Disease ◽

Mouse Model ◽

Bowel Disease ◽

Mode Of Action ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Health Issue ◽

The Public ◽

Inflammatory Bowel

The public has gradually begun to regard inflammatory bowel disease (IBD) as a crucial health issue; however, its mode of action has not been fully elucidated. Sophorolipid (SPL), a glycolipid-type...

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hucMSCs Attenuate IBD through Releasing miR148b-5p to Inhibit the Expression of 15-lox-1 in Macrophages

Mediators of Inflammation ◽

10.1155/2019/6953963 ◽

2019 ◽

Vol 2019 ◽

pp. 1-16 ◽

Cited By ~ 5

Author(s):

Jingjing Kang ◽

Zhaoyang Zhang ◽

Jingyan Wang ◽

Gaoying Wang ◽

Yongmin Yan ◽

...

Keyword(s):

Stromal Cells ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Inflammatory Cells ◽

Human Umbilical Cord ◽

Therapeutic Effects ◽

Body Weights ◽

Inflammatory Bowel ◽

The Relationship

Mesenchymal stem cells (MSCs) exert powerful immunosuppression in inflammatory bowel disease (IBD). Macrophages are the dominant inflammatory cells in enteritis regulated via MSCs. However, the roles of macrophages in the process of MSCs attenuating IBD and the mechanisms of MSCs regulating macrophages are largely unknown. In this study, DSS- (dextran sulfate sodium salt-) induced IBD in macrophage-depleted models of CD11b-DTR mice was used to study the relationship between hucMSCs (human umbilical cord mesenchymal stromal cells) and macrophage. Body weights, disease activities, and pathological changes were documented to assess the therapeutic effects of hucMSCs. Furthermore, hucMSCs transfected with miR148b-5p mimics and miR148b-5p inhibitors were cocultured with LPS-induced RAW264.7 cells to investigate the role of miR148b-5p in hucMSC-regulated colitis. The outcome indicated that hucMSCs attenuated the IBD by downregulating 15-lox-1 expression in macrophages. Further findings pointed out that hucMSCs transfected with miR148b-5p mimics could be elevated to promote the tissue repair and inhibit the expression of 15-lox-1 but failed to perform the function of easing enteritis when treated with miR148b-5p inhibitors. In conclusions, we propose that hucMSCs attenuate IBD by releasing miR148b-5p to inhibit the expression of 15-lox-1 in macrophages.

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