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Wild-Mouse-Derived Gut Microbiome Transplantation in Laboratory Mice Partly Alleviates House-Dust-Mite-Induced
Md Zohorul Islam1,2,3,4, Danica Jozipovic1, Pablo Atienza Lopez5
1Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark.
Abstract:
Laboratory mice are instrumental for preclinical research but there are serious concerns that the use of a clean standardized environment for specific-pathogen-free (SPF) mice results in poor bench-to-bedside translation due to their immature immune system. The aim of the present study was to test the importance of the gut microbiota in wild vs. SPF mice for evaluating host immune responses in a house-dust-mite-induced allergic airway inflammation model without the influence of pathogens. The wild mouse microbiome reduced histopathological changes and TNF-α in the lungs and serum when transplanted to microbiota-depleted mice compared to mice transplanted with the microbiome from SPF mice. Moreover, the colonic gene expression of Gata3 was significantly lower in the wild microbiome-associated mice, whereas Muc1 was more highly expressed in both the ileum and colon. Intestinal microbiome and metabolomic analyses revealed distinct profiles associated with the wild-derived microbiome. The wild-mouse microbiome thus partly reduced sensitivity to house-dust-mite-induced allergic airway inflammation compared to the SPF mouse microbiome, and preclinical studies using this model should consider using both 'dirty' rewilded and SPF mice for testing new therapeutic compounds due to the significant effects of their respective microbiomes and derived metabolites on host immune responses.
Insights
Wild mouse gut microbiota can reduce allergic airway inflammation in mice. This suggests that preclinical research should consider both wild and specific-pathogen-free mouse models for better therapeutic translation.
Area of Science:
- Immunology
- Microbiome Research
- Preclinical Models
Background:
- Specific-pathogen-free (SPF) mice in clean environments may have immature immune systems, impacting preclinical research translation.
- The gut microbiome's role in host immune responses, particularly in allergic diseases, is increasingly recognized.
Purpose of the Study:
- To investigate the influence of gut microbiota from wild versus SPF mice on allergic airway inflammation.
- To assess host immune responses in a house-dust-mite-induced asthma model using different microbiome compositions.
Main Methods:
- Transplantation of gut microbiota from wild and SPF mice into microbiota-depleted mice.
- Induction of house-dust-mite allergic airway inflammation.
- Analysis of histopathological changes, cytokine levels (TNF-α), and gene expression (Gata3, Muc1).
- Intestinal microbiome and metabolomic profiling.
Main Results:
- Wild mouse microbiome transplantation reduced lung and serum histopathology and TNF-α levels compared to SPF microbiome.
- Colonic Gata3 expression was lower, while Muc1 expression was higher in wild microbiome-associated mice.
- Distinct microbiome and metabolomic profiles were observed between wild and SPF-derived microbiomes.
- Wild mouse microbiome conferred partial protection against allergic airway inflammation.
Conclusions:
- Gut microbiota composition significantly impacts host immune responses to allergic airway inflammation.
- The wild mouse microbiome may offer a more robust immune profile for certain preclinical models.
- Preclinical studies should consider utilizing both 'rewilded' and SPF mouse models to account for microbiome-driven immune variations and improve therapeutic development.
