Gastrointestinal System Infection Modeling & Pharmacodynamics Services

Introduction

Gastrointestinal System infection diseases, such as viral gastroenteritis, bacterial Dysentery, and parasitic infections, caused by various pathogens, including Norovirus, Salmonella species, Shigella species, Escherichia coli (ETEC/EHEC), Clostridioides difficile (CDI), and Giardia lamblia, represent a significant global public health burden. These infections are among the leading causes of morbidity worldwide and are responsible for millions of hospitalizations and hundreds of thousands of deaths annually, particularly in children under five. The impact is particularly pronounced in low-resource settings with poor sanitation. Creative Biolabs provides a portfolio of specialized animal models that accurately replicate the clinical features of digestive system infectious diseases. These models can be used for the pharmacological and pharmacodynamic evaluation of oral antibiotics, antiviral drugs, enterotoxin neutralizers, microbiota therapies (FMT/probiotics), and oral vaccines, thereby accelerating the new drug development process.

Fig.1 The rotavirus replication cycle.¹

Available Gastrointestinal System Infection Models

Leveraging over a decade of dedicated expertise in infectious disease modeling, Creative Biolabs offers a robust array of well-characterized and clinically relevant digestive system infection animal models. These advanced models are designed to expedite your R&D process, ensuring efficient and reliable preclinical evaluation.

Measurements

Creative Biolabs assesses gastrointestinal system infection animal models by integrating an array of multi-dimensional technologies to comprehensively analyze disease mechanisms and drug efficacy, including but not limited to:

• Clinical Observation: Detailed recording of the animal models' symptoms (e.g., diarrhea, weight loss, dehydration, and body temperature changes).
• Pathogen Load and Identification: Accurate quantification of the pathogen load in feces, intestinal tissue, and blood is performed using quantitative PCR, ELISA, or viral culture and selective culture media. Strain identification is carried out using molecular subtyping.
• Histopathological Examination & Barrier Function: Focus is placed on inflammatory infiltration, ulceration, and tissue necrosis. Key assessment indicators include mucosal epithelial damage scoring and immunohistochemical analysis of Tight Junction proteins to evaluate intestinal barrier function.
• Molecular mechanism research: The expression profiles of inflammation-related genes are detected by RT-qPCR and RNA sequencing, to analyze the signal pathway activation mechanisms.
• Others: Intestinal microbiome analysis (16S rRNA / Metagenomics), metabolomics, and comprehensive mucosal immune analysis (e.g., Secretory IgA, lymphocyte subsets), among others.

Applications

• Disease Modeling: The models are used to simulate key pathological processes such as pathogen colonization, toxin release, epithelial damage, and microbiota dysbiosis within the gastrointestinal tract.
• Drug Discovery and Development: The models serve as essential platforms for screening oral antibiotics, antivirals, antitoxin agents, and evaluating the mucosal immune efficacy of oral vaccines.
• Therapeutic Strategy Optimization: The models are critical for validating the role of non-antibiotic interventions, such as Fecal Microbiota Transplantation (FMT), probiotics, and anti-virulence factors, in restoring gut microbiota and treating recurrent infections.
• Mechanism Study: The models dissect the multifaceted pathophysiology of enteric infections by reconstructing pathogen adhesion and invasion across the mucus-epithelial barrier, elucidating the molecular disruption of intercellular tight junctions, and characterizing the reciprocal interactions between the commensal microbiome, pathogenic agents, and mucosal immune defenses.

Our Advantages

• Comprehensive Model Library with Extensive Technical Expertise: Our library supports a wide variety of experimental animals, including mice, rats, dogs, and pigs, and can be customized to accommodate different pathogens and research requirements.
• Accurately simulate the disease process: We meticulously control the disease stage by regulating infection dose, cycle, and environmental factors to ensure precise simulation.
• Standardized Procedures and High-Quality Data Validation: A stringent model evaluation system is established for etiology verification, pathological assessment, and functional testing. Standardized modeling procedures (e.g., fasting before Helicobacter pylori infection) ensure consistency across multiple experimental batches, meeting the reliability requirements for drug screening and mechanistic research.
• Multi-dimensional technical platform support: We integrate platforms in molecular biology, immunology, virology, and pathology to provide comprehensive pharmacodynamic evaluations.
• One-Stop Service and Resource Integration: We offer customized, integrated solutions by flexibly adjusting model strategies based on drug type (e.g., small molecules, biologics) and research stage (e.g., target validation, safety evaluation). Our seamless service integrates all resources, from model development and PK/PD analysis to professional reporting, to accelerate preclinical development and eliminate vendor complexity.

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FAQs

1. Q: Why are in vivo GI models essential for testing new antimicrobials?

   A: The GI tract presents unique challenges (such as low pH, enzyme activity, and complex microbiota). In vivo models are essential tools for assessing the local stability of oral drugs, their bioavailability within the intestinal lumen, and their efficiency of transmucosal absorption, providing data that is more predictive than in vitro testing.

2. Q: Which specialized models do you use for Pharmacodynamic (PD) assessment in the GI tract?

   A: We utilize validated models such as the CDI hamster/mouse model, Salmonella/Shigella enteric fever models, and viral enteritis models. These platforms enable precise measurement of pathogen shedding, toxin levels, gut pathology (e.g., histology), and microbiota composition under drug challenge.

3. Q: How do you assess the impact of a new drug on the gut microbiome?

   A: We combine in vivo drug challenge with 16S rRNA gene sequencing and metagenomics analysis. This allows for quantitative assessment of the drug's effect on microbial diversity, specific bacterial populations, and the overall dysbiosis index, which is key for developing microbiota-sparing antibiotics.

4. Q: How does PD modeling accelerate the development of CDI therapeutics?

   A: For CDI, our PD modeling focuses on the relationship between drug exposure and toxin production and disease recurrence. We determine the optimal dose by combining 16S rRNA/metagenomic sequencing. This optimal dose is capable of maximizing bacterial clearance while minimizing disruption to the protective commensal microbiota, thereby reducing the risk of recurrence and accelerating clinical readiness.

5. Q: What commercial advantages do clients gain from your GI PD services?

   A: Our scientifically rigorous, in vivo-driven data package reduces attrition in later development stages by validating efficacy in a complex biological environment. This provides the data confidence necessary to attract investment and support compelling regulatory submissions for treating critical GI infections.

Published Data

The memory humoral immunity induced by C. difficile infection (CDI) is only targeted against the virulence toxins (TcdA/TcdB). Secondary infection significantly reinforces this IgG response, but shows no memory activation against surface proteins (SlpA/FliC), and the immunodominance of TcdA remains unchanged throughout. This finding provides a crucial direction for CDI vaccine development.

Fig.2 Serum IgG kinetics following primary and secondary infections.²

References

1. Amimo, Joshua Oluoch et al. "Rotavirus Interactions With Host Intestinal Epithelial Cells." Frontiers in immunology vol. 12 793841. https://doi.org/10.3389/fimmu.2021.793841. Distributed under Open Access license CC BY 4.0, without modification.
2. Mizrahi, Assaf et al. "A Mouse Model of Mild Clostridioides difficile Infection for the Characterization of Natural Immune Responses." Microorganisms vol. 12,10 1933. https://doi.org/10.3390/microorganisms12101933. Distributed under Open Access license CC BY 4.0, with modification.

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