95332 Intestinal inflammation and altered gut microbiota associated with inflammatory bowel disease render mice susceptible to Clostridioides difficile colonization and infection

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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Alteration of Gut Microbiota in Inflammatory Bowel Disease (IBD): Cause or Consequence? IBD Treatment Targeting the Gut Microbiome

Pathogens ◽

10.3390/pathogens8030126 ◽

2019 ◽

Vol 8 (3) ◽

pp. 126 ◽

Cited By ~ 52

Author(s):

Israr Khan ◽

Naeem Ullah ◽

Lajia Zha ◽

Yanrui Bai ◽

Ashiq Khan ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Gut Microbiota ◽

Bowel Disease ◽

Intestinal Inflammation ◽

Current Knowledge ◽

Pathological Condition ◽

Gut Flora ◽

Core Microbiome ◽

Inflammatory Bowel

Inflammatory bowel disease (IBD) is a chronic complex inflammatory gut pathological condition, examples of which include Crohn’s disease (CD) and ulcerative colitis (UC), which is associated with significant morbidity. Although the etiology of IBD is unknown, gut microbiota alteration (dysbiosis) is considered a novel factor involved in the pathogenesis of IBD. The gut microbiota acts as a metabolic organ and contributes to human health by performing various physiological functions; deviation in the gut flora composition is involved in various disease pathologies, including IBD. This review aims to summarize the current knowledge of gut microbiota alteration in IBD and how this contributes to intestinal inflammation, as well as explore the potential role of gut microbiota-based treatment approaches for the prevention and treatment of IBD. The current literature has clearly demonstrated a perturbation of the gut microbiota in IBD patients and mice colitis models, but a clear causal link of cause and effect has not yet been presented. In addition, gut microbiota-based therapeutic approaches have also shown good evidence of their effects in the amelioration of colitis in animal models (mice) and IBD patients, which indicates that gut flora might be a new promising therapeutic target for the treatment of IBD. However, insufficient data and confusing results from previous studies have led to a failure to define a core microbiome associated with IBD and the hidden mechanism of pathogenesis, which suggests that well-designed randomized control trials and mouse models are required for further research. In addition, a better understanding of this ecosystem will also determine the role of prebiotics and probiotics as therapeutic agents in the management of IBD.

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Intestinal Inflammation and Altered Gut Microbiota Associated with Inflammatory Bowel Disease Render Mice Susceptible to Clostridioides difficile Colonization and Infection

mBio ◽

10.1128/mbio.02733-20 ◽

2021 ◽

Author(s):

Lisa Abernathy-Close ◽

Madeline R. Barron ◽

James M. George ◽

Michael G. Dieterle ◽

Kimberly C. Vendrov ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Mouse Model ◽

Gut Microbiota ◽

Intestinal Inflammation ◽

Antibiotic Use ◽

Content Type ◽

Clostridioides Difficile ◽

Increased Risk ◽

Inflammatory Bowel ◽

The Relationship

The incidence of C. difficile infection (CDI) has increased significantly among patients with IBD, independently of antibiotic use, yet the relationship between IBD and increased risk for CDI remains to be understood. Our study sought to describe and utilize an antibiotic-independent mouse model to specifically explore the relationship between the IBD-associated gut and susceptibility to C. difficile colonization and CDI development.

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Dietary Composition and Effects in Inflammatory Bowel Disease

Nutrients ◽

10.3390/nu11061398 ◽

2019 ◽

Vol 11 (6) ◽

pp. 1398 ◽

Cited By ~ 2

Author(s):

Fernando Castro ◽

Heitor S. P. de Souza

Keyword(s):

Inflammatory Bowel Disease ◽

Gut Microbiota ◽

Bowel Disease ◽

Dietary Habits ◽

Intestinal Inflammation ◽

Dietary Factors ◽

Food Components ◽

Increased Risk ◽

Inflammatory Bowel ◽

Chronic Intestinal Inflammation

Dramatic changes in the environment and human lifestyle have been associated with the rise of various chronic complex diseases, such as inflammatory bowel disease (IBD). A dysbiotic gut microbiota has been proposed as a crucial pathogenic element, contributing to immune imbalances and fostering a proinflammatory milieu, which may be associated with disease relapses or even the initiation of IBD. In addition to representing important regulators of the mucosal immunity and the composition of the gut microbiota, food components have been shown to be potential environmental triggers of epigenetic modifications. In the context of chronic intestinal inflammation, dietary habits and specific food components have been implicated as important modulators of epigenetic mechanisms, including DNA methylation, which may predispose a person to the increased risk of the initiation and evolution of IBD. This review provides novel insights about how dietary factors may interact with the intestinal mucosa and modulate immune homeostasis by shaping the intestinal ecosystem, as well as the potential influence of diet in the etiopathogenesis and management of IBD.

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Alterations and Prediction of Functional Profiles of Gut Microbiota After Fecal Microbiota Transplantation for Iranian Recurrent Clostridioides difficile Infection with Underlying Inflammatory Bowel Disease: A Pilot Study

Journal of Inflammation Research ◽

10.2147/jir.s338212 ◽

2022 ◽

Vol Volume 15 ◽

pp. 105-116

Author(s):

Masoumeh Azimirad ◽

YoungJae Jo ◽

Min-Sueng Kim ◽

Minsoo Jeong ◽

Shabnam Shahrokh ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Pilot Study ◽

Gut Microbiota ◽

Bowel Disease ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Clostridioides Difficile ◽

Clostridioides Difficile Infection ◽

Inflammatory Bowel ◽

Functional Profiles

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A comparative study of different fucoidan on the cefoperazone-induced gut microbiota disturbance and intestinal inﬂammation

Food & Function ◽

10.1039/d1fo00782c ◽

2021 ◽

Author(s):

Juanmei Luo ◽

Zhan Wang ◽

Bin Fan ◽

Li Wang ◽

Mengyang Liu ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Gut Microbiota ◽

Comparative Study ◽

Bowel Disease ◽

Intestinal Inflammation ◽

Inflammatory Bowel ◽

Metabolic Syndromes

The abuse of antibiotics can lead to gut microbiota disturbance and intestinal inflammation, which may lead to serious inflammatory bowel disease and metabolic syndromes. To investigate the effect of fucoidan...

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Diet–Microbiota Interactions in Inflammatory Bowel Disease

Nutrients ◽

10.3390/nu13051533 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1533

Author(s):

Kohei Sugihara ◽

Nobuhiko Kamada

Keyword(s):

Inflammatory Bowel Disease ◽

Gut Microbiota ◽

Bowel Disease ◽

Intestinal Inflammation ◽

Current Knowledge ◽

Chronic Inflammatory Disease ◽

Host Cells ◽

Intestinal Homeostasis ◽

New Therapeutic Approaches ◽

Inflammatory Bowel

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract. Although the precise etiology of IBD is largely unknown, it is widely thought that diet contributes to the development of IBD. Diet shapes the composition of the gut microbiota, which plays critical roles in intestinal homeostasis. In contrast, intestinal inflammation induces gut dysbiosis and may affect the use of dietary nutrients by host cells and the gut microbiota. The interaction of diet and the gut microbiota is perturbed in patients with IBD. Herein, we review the current knowledge of diet and gut microbiota interaction in intestinal homeostasis. We also discuss alterations of diet and gut microbiota interaction that influence the outcome and the nutritional treatment of IBD. Understanding the complex relationships between diet and the gut microbiota provides crucial insight into the pathogenesis of IBD and advances the development of new therapeutic approaches.

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