Kinetic and mechanistic diversity of intestinal immune homeostasis characterized by rapid removal of gut bacteria
Da-Jung Jung,
Ledia Gebremedhin,
Byoungsook Goh,
Ji-Sun Yoo,
Francesca Gazzaniga,
Dennis L. Kasper,
Sungwhan F. Oh
Affiliations
Da-Jung Jung
Center for Experimental Therapeutics and reperfusion injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA, USA
Ledia Gebremedhin
Center for Experimental Therapeutics and reperfusion injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA, USA
Byoungsook Goh
Center for Experimental Therapeutics and reperfusion injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA, USA
Ji-Sun Yoo
Center for Experimental Therapeutics and reperfusion injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA, USA
Francesca Gazzaniga
Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA
Dennis L. Kasper
Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA
Sungwhan F. Oh
Center for Experimental Therapeutics and reperfusion injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA, USA
ABSTRACTSymbiotic 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.
