Related Experiment Video
Updated: Jul 13, 2026
Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice
Published on: April 21, 2015
Shift towards pro-inflammatory intestinal bacteria aggravates acute murine colitis via Toll-like receptors 2 and 4
Markus M Heimesaat1, André Fischer, Britta Siegmund
1Institut für Mikrobiologie und Hygiene, Charité - Universitätsmedizin Berlin, Charité Campus Mitte, Berlin, Germany.
Background:
Gut bacteria trigger colitis in animal models and are suspected to aggravate inflammatory bowel diseases. We have recently reported that Escherichia coli accumulates in murine ileitis and exacerbates small intestinal inflammation via Toll-like receptor (TLR) signaling.
Methodology And Principal Findings:
Because knowledge on shifts in the intestinal microflora during colitis is limited, we performed a global survey of the colon flora of C57BL/10 wild-type (wt), TLR2(-/-), TLR4(-/-), and TLR2/4(-/-) mice treated for seven days with 3.5% dextrane-sulfate-sodium (DSS). As compared to wt animals, TLR2(-/-), TLR4(-/-), and TLR2/4(-/-) mice displayed reduced macroscopic signs of acute colitis and the amelioration of inflammation was associated with reduced IFN-gamma levels in mesenteric lymph nodes, lower amounts of neutrophils, and less FOXP3-positive T-cells in the colon in situ. During acute colitis E. coli increased in wt and TLR-deficient mice (P<0.05), but the final numbers reached were significantly lower in TLR2(-/-), TLR4(-/-) and TLR2/4(-/-) animals, as compared to wt controls (P<0.01). Concentrations of Bacteroides/ Prevotella spp., and enterococci did not increase during colitis, but their numbers were significantly reduced in the colon of DSS-treated TLR2/4(-/-) animals (P<0.01). Numbers of lactobacilli and clostridia remained unaffected by colitis, irrespective of the TLR-genotype of mice. Culture-independent molecular analyses confirmed the microflora shifts towards enterobacteria during colitis and showed that the gut flora composition was similar in both, healthy wt and TLR-deficient animals.
Conclusions And Significance:
DSS-induced colitis is characterized by a shift in the intestinal microflora towards pro-inflammatory Gram-negative bacteria. Bacterial products exacerbate acute inflammation via TLR2- and TLR4-signaling and direct the recruitment of neutrophils and regulatory T-cells to intestinal sites. E. coli may serve as a biomarker for colitis severity and DSS-induced barrier damage seems to be a valuable model to further identify bacterial factors involved in maintaining intestinal homeostasis and to test therapeutic interventions based upon anti-TLR strategies.
Insights
Gut bacteria shifts, particularly Escherichia coli, worsen colitis by activating Toll-like receptors (TLRs). TLR deficiency reduces inflammation and bacterial overgrowth, suggesting TLRs as therapeutic targets for inflammatory bowel diseases.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Gut bacteria are implicated in triggering colitis and exacerbating inflammatory bowel diseases.
- Escherichia coli accumulation in the ileum exacerbates small intestinal inflammation via Toll-like receptor (TLR) signaling.
Purpose of the Study:
- To investigate shifts in the colon microflora during dextran-sulfate-sodium (DSS)-induced colitis.
- To determine the role of Toll-like receptors (TLRs) 2 and 4 in modulating the gut microbiota and inflammatory responses during colitis.
Main Methods:
- Global survey of colon flora in wild-type (wt), TLR2(-/-), TLR4(-/-), and TLR2/4(-/-) mice treated with DSS.
- Analysis of macroscopic signs of colitis, IFN-gamma levels, neutrophil counts, and FOXP3-positive T-cells.
- Culture-independent molecular analyses to confirm microflora shifts.
Main Results:
- TLR-deficient mice showed reduced macroscopic signs of colitis, lower IFN-gamma, fewer neutrophils, and less FOXP3-positive T-cells.
- Escherichia coli increased in wt and TLR-deficient mice during colitis, but significantly less in TLR-deficient animals.
- DSS-induced colitis shifted the gut microflora towards Enterobacteria, with reduced Bacteroides/Prevotella spp. and enterococci in TLR2/4(-/-) mice.
Conclusions:
- DSS-induced colitis involves a shift towards pro-inflammatory Gram-negative bacteria, exacerbated by bacterial products via TLR2 and TLR4 signaling.
- TLR signaling directs neutrophil and regulatory T-cell recruitment to the intestine.
- Escherichia coli may serve as a biomarker for colitis severity, and DSS models can test anti-TLR therapies.
More Related Videos
07:34Induction of Intestinal Inflammation by Adoptive Transfer of CBir1 TCR Transgenic CD4+ T Cells to Immunodeficient Mice
Published on: December 16, 2021
06:57Development of an Antigen-driven Colitis Model to Study Presentation of Antigens by Antigen Presenting Cells to T Cells
Published on: September 18, 2016
Related Concept Videos
01:25Inflammatory Bowel Disease III: Crohn's Disease
01:20Inflammatory Bowel Disease II: Ulcerative Colitis
01:18Dysbiosis of the Gut Microbiota
01:26Inflammatory Bowel Disease I: Introduction
01:27Inflammatory Bowel Disease I: Ulcerative Colitis
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
01:30Inflammatory Bowel Disease II: Crohn's Disease
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by transmural...