TABLE 4.
Advantages and pitfalls of gnotobiotic animal models in comparison with human research, with respect to the factors influencing intestinal microbiota composition or behaviora
| Factor | Advantage(s) (vs human research) | Pitfalls in practice |
|---|---|---|
| Inoculum (defined community) | Controllable composition (healthy vs diseased microbiota [e.g., missing keystone species], human vs animal derived) | Animal microbiome ≠ human microbiome; difficulties in defining a healthy or normal microbiota; host-specific selection of microbiota |
| Diet | Controllable composition, timing, amt (tailored to human diet [region, age, and season, etc.]) | Lack of standardization in laboratory animal feeding protocols; not always reportedb |
| Host genotype | Controllable; genetic changes possible (ability to introduce disease) | Validation of host-microbe interactions in multiple strains needed before extrapolation to humans; animal genotype ≠ human genotype |
| Sex | Controllable | Only one gender investigatedb; not always reportedb |
| Part of the gut | Ability to measure bacterial levels in virtually all intestinal parts; ability to capture transversal heterogeneity | Anatomy and physiology different from humans; variations in relative abundances per gut region different per modelb; focus on specific gut regions or feces onlyb |
| Colonization time | Controllable | Long-term effects not studiedb ; animals not always colonized starting at birthb; stability over generations not always confirmedb |
| Immune system | Controllable at start/birth | Uncontrollable in long-term studies, especially locally; complex, determined by internal and external factors; not quantified or quantifiableb |