Comparing Animal Models of IBD
Each animal model has unique features that make them suitable for different study questions and different labs. Understanding the benefits and limitations (summarized in Table 1) of each animal model is critical for selecting the appropriate model for you.
Mice and Rats: The most common model
Mice are the most commonly used animal model for intestinal studies due to their numerous advantages:
- Easy to genetically modify
- Many genetically modified mouse lines are available
- Efficient husbandry
- Similar to the human microbiome, immune responses, and monogastric anatomy, and intestine function
Because it is relatively easy to generate or obtain genetically modified mice that produce a desired phenotype, researchers can investigate innate and adaptive immune responses and various aspects of intestinal inflammation—making mouse models suitable for a variety of study types.
While there are many advantages to using mouse models, there are some disadvantages. Intestinal lesions (following chemical induction) are not identical to those in people with IBD, coprophagy can potentially confound nutritional studies, and the tissue sample sizes that can be harvested from an individual mouse is small, which may require samples to be pooled for analysis.
An alternative rodent model is the rat—which is larger and suitable for studies investigating the intestinal microbial community structure and dietary impact on intestinal inflammation.
Learn more about how to induce colitis in various mouse strains.
Nematodes and Insects: Unconventional but high-throughput
Nematodes (e.g., C. elegans) and insects (e.g., D. malanogaster) are small and lack an adaptive immune system but they do share some similarities with mammalian intestines:
- Modified innate intestinal immune system
- Antimicrobial peptide production
- Signalling pathways
- Host-microbial interactions within the intestine
These similarities paired with their low cost and rapid gestation periods make them advantageous to use for studying early processes involved in intestinal inflammation. The major disadvantage to using nematodes and insects is the lack of an adaptive immune response, making their applications limited.
Zebrafish: Versatile and cost-effective
Unlike nematodes and insects, zebrafish can be used to study the innate and adaptive immune response, and they have several more organs that show pathological changes upon IBD induction—making them a superior and versatile invertebrate model.
With a transparent embryo and larvae, simple husbandry requirements, and germ-free options, zebrafish are suitable for a variety of studies and approaches such as real-time imaging during infection, microbiome investigation, and exploring intestinal motility and peristaltic events. Notably, zebrafish lack a defined stomach, so nutritional studies are limited.
Pigs: Anatomically and functionally similar
Pigs are advantageous for studying intestinal injury and inflammation for several reasons:
- Large size, so the harvest tissue to analysis will be enough (although the amount of tissue could get overwhelming)
- Similar intestinal anatomy and function to human intestine
- Similar intestinal enzymes and microbiome to humans
- Similar intestinal immune response to human immunity
- Easy to genetically modify
The disadvantages to using pigs are related to cost, size, and time. Because of their large size, the housing and husbandry requirements can be a substantial cost, and their slow growth rate and several-month gestation period can cause long study periods.
Non-Human Primate: The most representative model
Non-human primates (NHPs) are the best animal models to use in terms of comparability to humans, however there are significant ethical and biosafety concerns that must be considered when using these animals.
Because of their similarity to humans, it is unsurprising that these animals can spontaneously and chronically develop colitis, making them particularly useful for the natural progression of IBD without using biological or chemical incitants (although these can be used if needed).
Further, NHPs offer great insights into the gut-brain axis, the intestinal microbiome, and mental health as researchers can study the impact of feeding behavior, stress, depression, and pain on IBD.
In addition to the ethical and biosafety concerns, researchers need to consider the substantial costs associated with environmental enrichment, husbandry, housing, and personnel training.
If you decide to go with NHPs as your animal model, we thank you for pursuing such translatable data, but please do it safely and ethically!
Uncommon Animal Models of IBD
Because IBD is multifactorial and involves organs and mechanisms shared by many animals, there are several animal models of IBD beyond what has been discussed above. The less frequently used animals include dogs, guinea pigs, ruminants, and rabbits. Notably, these models (especially sheep) are particularly useful as surgical models (e.g., intestinal loop studies).
Table 1: A summary of the advantages and disadvantages of different animal models of IBD
| Animal Model |
Key Advantages |
Key Disadvantages |
Recent Studies |
| Nematodes & Insects |
- High-throughput
- Cost-effective
- Easy to genetically modify
- Minimal ethical concerns
|
- No adaptive component
- No complex microbiome research
- Relevance to human pathology is limited
|
Kumar, Arun, et al. "Caenorhabditis elegans: a model to understand host–microbe interactions." Cellular and Molecular Life Sciences 77.7 (2020): 1229-1249.
|
| Zebrafish |
- Cost-effective
- Invertebrate with innate and adaptive immune
- Transparent embryo and larvae
- Simple husbandry
- Germ-free options
|
- Small tissue size
- Lack a defined stomach
- Cannot do diet or nutritional comparisons
|
Notararigo, Sara, et al. "Evaluation of an O2-Substituted (1–3)-β-D-Glucan, Produced by Pediococcus parvulus 2.6, in ex vivo Models of Crohn’s Disease." Frontiers in microbiology 12 (2021): 88.
|
| Rodent |
- Easy genetic manipulation
- Germ-free options
- Microbiome similarities to humans
- Well characterized, common model
|
- Small tissue size in mouse models
- Coprophagy
- Costs associated with Level 2 facilities
|
Ko, Hyun-Jeong, et al. "Plasmacytoid dendritic cells regulate colitis-associated tumorigenesis by controlling myeloid-derived suppressor cell infiltration." Cancer Letters 493 (2020): 102-112.
|
| Pigs |
- Easy genetic modification
- Anatomically and functionally similar intestine
- Microbiome similar to humans
- Abundance of tissue
- Germ-free options
|
- Cost of Level 2 facilities
- Long gestation periods
- Personnel training needs
- Slight variation in immune cells and large intestine orientation
|
Diao, H., et al. "Effects of Early Transplantation of the Faecal Microbiota from Tibetan Pigs on the Gut Development of DSS-Challenged Piglets." BioMed research international 2021 (2021).
|
| Non-Human Primate |
- Most comparable to humans genetically, anatomically, behaviorally, and within the microbiome
- Human disease presents similar to humans
- Abundance of tissue
|
- Ethical and biosafety concerns
- Level 2 facilities
- Personnel training
- Substantial costs
|
Compo, Nicole R., Luis Mieles-Rodriguez, and Diego E. Gomez. "Fecal Bacterial Microbiota of Healthy Free-Ranging, Healthy Corralled, and Chronic Diarrheic Corralled Rhesus Macaques (Macaca mulatta)." Comparative Medicine (2021).
|
| Dogs, Guinea Pigs, Rabbits, Ruminants |
- Intestinal loop models
- Abundance of tissues
- Enteric pathogen studies
- Microbiome studies
- Easy genetic modification (some models)
|
- Long gestation periods
- Level 2 facilities
- Husbandry and personnel training
- Not well studied
|
Liaskos, Christos, et al. "Pancreatic anti-GP2 and anti-Saccharomyces cerevisiae antibodies in ruminants with paratuberculosis: A better understanding of the immunopathogenesis of Crohn's disease." Clinics and research in hepatology and gastroenterology 44.5 (2020): 778-785.
|
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