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

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.

Automated summary

Symbiotic microbiota play a critical role in maintaining host immune homeostasis in a cell-specific manner. Germ-free animals have been the gold standard for excluding microbial components but complete removal of gut microbiota from birth can impair physiological development. Using an improved regimen, we were able to rapidly remove gut microbiota and maintain sterility in animals without any adverse reactions. This method allowed us to observe kinetic differences among colonic lymphocyte subsets that are not observed in traditional germ-free animal models. Additionally, we were able to distinguish between direct stimulation and homeostatic cues of microbiota contribution to effector cell function.