Simple Animal Models for Live Biotherapeutic Products Assessment

Creative Biolabs is the world's leading live biotherapeutics (LBP) contract research organization providing end-to-end solutions to our partners, and we have built one of the largest and most experienced development teams in the world to ensure we have the resources and expertise, to help your project most efficiently and cost-effectively.

Modeling Host-Microbiome Interactions in Simple Animals

When studying in vivo models of LBP risk recording, simple animal models such as Drosophila melanogaster (D. melanogaster) or Caenorhabditis elegans (C. elegans) may help decipher pathways within the host. C. elegans could be a suitable model to understand whether the host, the microbe, or the environment, determines the susceptibility or resistance to infections. Immunodeficient D. melanogaster could also be used to better understand mechanisms involved in the possible transition from symbiotic to pathogenic microorganisms and could also offer a platform to screen microbe-xenobiotic in vivo interactions, providing insight into safety outcomes potentially related to the metabolism of regular drugs by the microbiome. The ideal model organism should have the following characteristics: high-throughput screening ability, rapid reproduction, low cost, and easy-to-manipulate microbiota.

Simple Animal Models at Creative Biolabs

  • C. elegans

The microbiome influences host processes, including nutrient availability, development, immunity, and behavioral responses. C. elegans is a powerful model to study molecular mechanisms of host-microbial interactions. The ease of maintenance of sterile worms, high throughput applicability, and relatively short lifespan make C. elegans a practical choice for studying interactions between host, microbiome, and environment.

  • Genetics of Host-microbiome Interactions

C. elegans is suitable to study the effects of host-microbiome interactions in a semi-high-throughput manner. A combination of C. elegans and bacterial genetic screening reveals novel host-microbe interaction mechanisms.

  • Fat Metabolism

Microbiomes dominated by Firmicutes rather than Bacteroides have been associated with obesity in humans. The lactic acid bacteria (LAB) microbial reduced worm lifespan, led to the accumulation of lipid droplets, and altered expression of obesity phenotypic genes NHR-49, PEPT-1, and TUB-1 compared with animals fed conventional Escherichia coli.

  • Microbiome and Host-pathogen Interactions

The protective mechanism of bacteria was studied using the C. elegans model. Lactobacillus casei protects C. elegans from the effects of Klebsiella pneumonia. Four strains of Lactobacillus plantarum initially isolated from infant feces persisted in the nematode gut and significantly extended nematode lifespan and improved nematode survival after exposure to pathogenic S. aureus.

  • D. melanogaster

D. melanogaster is an excellent model organism to reliably verify the effects of probiotics in living organisms. Compared with mice or humans, D. melanogaster has a simple microbiota with low microbial diversity, dominated by Lactobacillus and Acetobacter. This simplified community structure removes the complexity of deciphering the effects of a particular microbial species on the larger community and its host. In conclusion, D. melanogaster experiments are affordable, convenient, and rarely require animal ethics review board approval. These properties make D. melanogaster an ideal high-throughput in vivo model for understanding the host microbiota.

Simple animal models for microbiome research.Fig.1 Simple animal models for microbiome research. (Douglas, 2019)

When LBPs are used as drugs, sufficient CMC information must be provided to ensure safety. The proposed use of simple animals as an in vivo model for drug discovery with greater predictive validity than in vitro assays. Creative Biolabs' team of highly qualified and experienced technical staff will work with you to develop and deliver testing solutions to add value to your product or project. Please feel free to contact us to learn more about our simple animal models.

Reference

  1. Douglas, A.E. Simple animal models for microbiome research. Nature Reviews Microbiology. 2019, 17(12): 764-775.

For Research Use Only. Not intended for use in food manufacturing or medical procedures (diagnostics or therapeutics). Do Not Use in Humans.

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For Research Use Only. Not intended for use in food manufacturing or medical procedures (diagnostics or therapeutics). Do Not Use in Humans.

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