IBD Models: A Guide to Using DSS and TNBS

Introduction: Approaching Complex IBD Pathology

Inflammatory Bowel Disease (IBD) is a group of disorders comprising distinct pathologies like Ulcerative Colitis (UC) and Crohn's Disease (CD), and selecting the appropriate model for the purpose is essential for drug discovery research. The most commonly used are the Dextran Sulfate Sodium (DSS)-induced colitis model and the TNBS-induced colitis model, but failure to correctly understand their respective characteristics and limitations can lead to unexpected misinterpretation of data.

Challenges in Research: Lack of Reproducibility and Subjectivity of Evaluation

1. "Lot Differences" in DSS and the Impact of "Microbiota"

The DSS model is considered simple and highly reproducible, but in reality, severity changes dramatically depending on the "molecular weight" and "sulfur content" lot differences of the DSS reagent used (Gastroenterology). Also, differences in "Gut Microbiota" due to housing environments or mouse suppliers (vendors) significantly affect DSS sensitivity. Troubles such as "inflammation did not occur this time even though it was done under the same conditions as last time (or the mortality rate was too high)" frequently occur when management of these factors is insufficient.

2. Technical Difficulty and Immunological Bias of the TNBS Model

The TNBS model induces a Th1/Th17-dominant immune response and presents transmural inflammation close to Crohn's disease, making it useful for elucidating immunological mechanisms. However, the enema administration technique is difficult, and if the balance between the barrier-disrupting effect of ethanol and the haptenization of TNBS is lost, there is a risk that it will become a mere chemical burn. Also, compared to DSS, individual variability is large, requiring a larger number of animals (N).

3. Subjectivity of Scoring

Conventionally used DAI (Disease Activity Index) scores and histological scores are easily influenced by the subjectivity of the evaluator, making data comparison between facilities difficult.

Solution: Introduction of Pre-validation and Endoscopic Analysis

1. Stabilization via "Pre-validated DSS"

At our partner CRO, we conduct preliminary tests for each incoming DSS lot to determine the optimal concentration setting (e.g., 2.5% vs 3.0%) and use "Pre-validated DSS." Also, to minimize the influence of gut microbiota, we use animals from the same vendor and barrier system and strictly manage the acclimatization period, thereby constantly reproducing a consistent severity (Mild/Moderate/Severe).

2. "Longitudinal and Objective" Evaluation via Small Animal Endoscopy

We have adopted MEICS (Murine Endoscopic Index of Colitis Severity) evaluation using an ultra-thin endoscope for mice as a standard (Gastroenterology).

• Longitudinal Observation: Inflammation progression in the same individual can be tracked at Day 0, 7, 14... without sacrifice. This enables "Paired analysis" that eliminates the influence of individual differences, improving statistical power.
• Objective Image Data: Vascular translucency, mucosal thickening, bleeding, etc., are recorded as high-resolution images, and objectivity is ensured by having a blinded third party perform the scoring.

Conclusion

"Data became unobtainable because the DSS lot changed." "I want to see the healing process in vivo, not just tissue sections." We respond to these needs in IBD research with strict quality control and the latest evaluation technologies. We will propose the optimal test system tailored to the pathology of UC/CD, so please feel free to contact us.

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References

1. Chassaing B, et al. Dextran sulfate sodium (DSS)-induced colitis in mice. Curr Protoc Immunol. 2014;104:15.25.1-15.25.14.
2. Neurath MF, et al. TNBS-colitis. Int Rev Immunol. 2000;19(1):51-62.
3. Becker C, et al. In vivo imaging of colitis and colon cancer development in mice using high resolution chromoendoscopy. Gut. 2005;54(7):950-954.