Dose-response framework for DSS-induced colitis in mice

Area of Science:

• Gastroenterology
• Immunology
• Microbiology

Background:

• Dextran sulfate sodium (DSS) is a common agent for inducing colitis in animal models.
• Inconsistent DSS dosing protocols hinder reproducibility and cross-study comparisons.
• A standardized dose-response framework is needed for reliable colitis modeling.

Purpose of the Study:

• To establish a graded Dextran sulfate sodium (DSS) dose-response framework for modeling colitis.
• To integrate pathological, microbial, transcriptomic, and immune profiling across a range of DSS concentrations.
• To provide guidance for selecting DSS doses based on experimental objectives and desired disease severity.

Main Methods:

• Administered varying concentrations of DSS (0%, 1.5%, 2.0%, 2.5%, 3.0%) to C57BL/6J mice.
• Integrated pathological, microbial, transcriptomic, and immune profiling.
• Analyzed dose-dependent effects on epithelial injury, inflammation, and immune cell infiltration.

Main Results:

• Low-dose DSS (1.5%-2.0%) induced mild, reversible injury and microbiota changes.
• Higher DSS doses (2.5%-3.0%) resulted in sustained inflammation and severe mucosal damage.
• Transcriptomic analysis revealed dose-dependent activation of key inflammatory pathways (TNF, NF-κB, IL-17, NOD-like receptor signaling).

Conclusions:

• The established DSS dose-response framework enables rational selection of concentrations for colitis modeling.
• This framework facilitates reproducible and comparable studies by defining dose-dependent outcomes.
• Understanding these dose-response relationships is crucial for advancing colitis research.