The Role of Estrogen Signaling in a Mouse Model of Inflammatory Bowel Disease: A Helicobacter Hepaticus Model

Clostridioides difficile has emerged as a noteworthy pathogen in patients with inflammatory bowel disease (IBD). Concurrent IBD and CDI is associated with increased morbidity and mortality compared to CDI alone. IBD is associated with alterations of the gut microbiota, an important mediator of colonization resistance to C. difficile. Here, we describe and utilize a mouse model to explore the role of intestinal inflammation in susceptibility to C. difficile colonization and subsequent disease severity in animals with underlying IBD. Helicobacter hepaticus, a normal member of the mouse gut microbiota, was used to trigger inflammation in the distal intestine akin to human IBD in mice that lack intact IL-10 signaling. Development of IBD resulted in a distinct intestinal microbiota community compared to non-IBD controls. We demonstrate that in this murine model, IBD was sufficient to render mice susceptible to C. difficile colonization. Mice with IBD were persistently colonized by C. difficile, while genetically identical non-IBD controls were resistant to C. difficile colonization. Concomitant IBD and CDI was associated with significantly worse disease than unaccompanied IBD. IL-10-deficient mice maintained gut microbial diversity and colonization resistance to C. difficile in experiments utilizing an isogenic mutant of H. hepaticus that does not trigger intestinal inflammation. These studies in mice demonstrate that the IBD-induced microbiota is sufficient for C. difficile colonization and that this mouse model requires intestinal inflammation for inducing susceptibility to CDI in the absence of other perturbations, such as antibiotic treatment.

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The role of osteopontin (OPN/SSP1) gene variants in inflammatory bowel disease

Zeitschrift für Gastroenterologie ◽

10.1055/s-0029-1241334 ◽

2009 ◽

Vol 47 (09) ◽

Author(s):

J Glas ◽

J Seiderer ◽

HP Török ◽

B Göke ◽

T Ochsenkühn ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Gene Variants ◽

Inflammatory Bowel

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Nutrition in inflammatory bowel disease

Orvosi Hetilap ◽

10.1556/oh.2009.28599 ◽

2009 ◽

Vol 150 (18) ◽

pp. 839-845 ◽

Cited By ~ 2

Author(s):

János Banai

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Fast Food ◽

Optimal Growth ◽

Developed Countries ◽

Aetiological Factor ◽

Artificial Nutrition ◽

Food Preservatives ◽

Inflammatory Bowel

Aetiology of inflammatory bowel disease (IBD) is complex and probably multifactorial. Nutrition has been proposed to be an important aetiological factor for development of IBD. Several components of the diet (such as sugar, fat, fibre, fruit and vegetable, protein, fast food, preservatives etc.) were examined as possible causative agents for IBD. According to some researchers infant feeding (breast feeding) may also contribute to the development of IBD. Though the importance of environmental factors is evidenced by the increasing incidence in developed countries and in migrant population in recent decades, the aetiology of IBD remained unclear. There are many theories, but as yet no dietary approaches have been proved to reduce the risk of developing IBD. The role of nutrition in the management of IBD is better understood. The prevention and correction of malnutrition, the provision of macro- and micronutrients and vitamins and the promotion of optimal growth and development of children are key points of nutritional therapy. In active disease, the effective support of energy and nutrients is a very important part of the therapy. Natural and artificial nutrition or the combination of two can be choosen for supporting therapy of IBD. The author summarises the aetiological and therapeutic role of nutrition in IBD.

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Faculty Opinions recommendation of Commensal Bacteroides species induce colitis in host-genotype-specific fashion in a mouse model of inflammatory bowel disease.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.11022957.12248054 ◽

2011 ◽

Author(s):

Asma Nusrat ◽

Stefan Koch

Keyword(s):

Inflammatory Bowel Disease ◽

Mouse Model ◽

Bowel Disease ◽

Host Genotype ◽

Bacteroides Species ◽

Inflammatory Bowel

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Role of Rifaximin in Inflammatory Bowel Disease Treatment

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557515666150722104230 ◽

2015 ◽

Vol 16 (3) ◽

pp. 225-229 ◽

Cited By ~ 2

Author(s):

Maria Lia Scribano

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Disease Treatment ◽

Inflammatory Bowel

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Tu1789 – Treatment Response to Ustekinumab and Vedolizumab in Inflammatory Bowel Disease: the Predictive Role of Gut Microbiota

Gastroenterology ◽

10.1016/s0016-5085(19)39775-6 ◽

2019 ◽

Vol 156 (6) ◽

pp. S-1124

Author(s):

Clara Caenepeel ◽

Sara Vieira-Silva ◽

Jorge F. Vázquez-Castellanos ◽

Bram Verstockt ◽

Marc Ferrante ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Gut Microbiota ◽

Treatment Response ◽

Bowel Disease ◽

Predictive Role ◽

Inflammatory Bowel

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The role of heme oxygenase and carbon monoxide in inflammatory bowel disease

Redox Report ◽

10.1179/174329210x12650506623889 ◽

2010 ◽

Vol 15 (5) ◽

pp. 193-201 ◽

Cited By ~ 20

Author(s):

Tomohisa Takagi ◽

Yuji Naito ◽

Kazuhiko Uchiyama ◽

Toshikazu Yoshikawa

Keyword(s):

Inflammatory Bowel Disease ◽

Carbon Monoxide ◽

Heme Oxygenase ◽

Bowel Disease ◽

Inflammatory Bowel

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Multi-Omics Characterization of Inflammatory Bowel Disease-Induced Hyperplasia/Dysplasia in the Rag2−/−/Il10−/− Mouse Model

International Journal of Molecular Sciences ◽

10.3390/ijms22010364 ◽

2020 ◽

Vol 22 (1) ◽

pp. 364

Author(s):

Qiyuan Han ◽

Thomas J. Y. Kono ◽

Charles G. Knutson ◽

Nicola M. Parry ◽

Christopher L. Seiler ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Gastrointestinal Disease ◽

Tumor Development ◽

Proximal Colon ◽

Helicobacter Hepaticus ◽

Reduced Representation ◽

Reduced Representation Bisulfite Sequencing ◽

Inflammatory Bowel

Epigenetic dysregulation is hypothesized to play a role in the observed association between inflammatory bowel disease (IBD) and colon tumor development. In the present work, DNA methylome, hydroxymethylome, and transcriptome analyses were conducted in proximal colon tissues harvested from the Helicobacter hepaticus (H. hepaticus)-infected murine model of IBD. Reduced representation bisulfite sequencing (RRBS) and oxidative RRBS (oxRRBS) analyses identified 1606 differentially methylated regions (DMR) and 3011 differentially hydroxymethylated regions (DhMR). These DMR/DhMR overlapped with genes that are associated with gastrointestinal disease, inflammatory disease, and cancer. RNA-seq revealed pronounced expression changes of a number of genes associated with inflammation and cancer. Several genes including Duox2, Tgm2, Cdhr5, and Hk2 exhibited changes in both DNA methylation/hydroxymethylation and gene expression levels. Overall, our results suggest that chronic inflammation triggers changes in methylation and hydroxymethylation patterns in the genome, altering the expression of key tumorigenesis genes and potentially contributing to the initiation of colorectal cancer.

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