Kinetic and mechanistic diversity of intestinal immune homeostasis characterized by rapid removal of gut bacteria

ABSTRACT

Symbiotic microbiota critically contribute to host immune homeostasis in effector cell-specific manner. For exclusion of microbial component, germ-free animals have been the gold standard method. However, total removal of the entire gut microbiota of an animal from birth significantly skews physiological development. On the other hand, removal of gut microbiota from conventional mice using oral antibiotics has its own limitations, especially lack of consistency and the requirement for long-term treatment period. Here, we introduce an improved regimen to quickly remove gut microbiota and to maintain sterility, that is well received by animals without refusal. Rapid and consistent exclusion of resident bacteria in the gut lumen revealed kinetic differences among colonic lymphocyte subsets, which cannot be observed with typical germ-free animal models. Furthermore, the proposed method distinguished the mechanism of microbiota contribution as a direct stimulus to capable effector cells and a homeostatic cue to maintain such cell types.

KEYWORDS:

• Germ-free mice
• antibiotic treatment
• mucosal immunology
• gut microbiota

Acknowledgments

We thank P. Guttry for manuscript preparation, W. Zheng and T. Yanostang for technical assistance.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2201154

Additional information

Funding

The work was supported by the National Center for Complementary and Integrative Health [R01-AT010268, S.F.O.]; National Institute of Allergy and Infectious Diseases [R01-AI165987, S.F.O.]; National Research Foundation of Korea [2021R1A6A3A14039202, D-J.J.]; National Research Foundation of Korea [2021R1A6A3A14044113, J-S.Y.].