	US 11,807,871 B2
	Complex human gut microbiome cultured in an anaerobic human gut-on-a-chip
Richard Novak, Boston, MA (US); Sasan Jalili-Firoozinezhad, Cambridge, MA (US); Francesca S. Gazzaniga, Jamaica Plain, MA (US); Elizabeth L. Calamari, Ashland, MA (US); Diogo M. Camacho, Framingham, MA (US); Bret A. Nestor, Regina (CA); Cicely Fadel, Brookline, MA (US); Michael L. Cronce, Roxbury, MA (US); Dennis L. Kasper, Boston, MA (US); Donald E. Ingber, Boston, MA (US); and Amir Bein, Cambridge, MA (US)
Assigned to President and Fellows of Harvard College, Cambridge, MA (US)
Appl. No. 15/733,716
Filed by President and Fellows of Harvard College, Cambridge, MA (US)
PCT Filed Apr. 2, 2019, PCT No. PCT/US2019/025460 § 371(c)(1), (2) Date Oct. 2, 2020, PCT Pub. No. WO2019/195344, PCT Pub. Date Oct. 10, 2019.
Claims priority of provisional application 62/722,658, filed on Aug. 24, 2018.
Claims priority of provisional application 62/651,438, filed on Apr. 2, 2018.
Prior Publication US 2021/0079356 A1, Mar. 18, 2021
Int. Cl. C12N 5/071 (2010.01); C12M 3/06 (2006.01); C12N 1/20 (2006.01); C12M 3/00 (2006.01)

CPC C12N 5/0679 (2013.01) [C12M 21/08 (2013.01); C12M 23/16 (2013.01); C12N 1/20 (2013.01)]

11 Claims

1. A method for establishing a stable complex community of gut commensal microbes in vitro, the method comprising:

providing cultured cells of an intestinal epithelium and microbiota from a mammalian fecal sample in an environment having a first level of oxygen, the microbiota being in direct and indirect contact with the intestinal epithelium, said fecal sample comprising a diluted fecal slurry and comprising both anaerobic bacteria and aerobic bacteria;

providing cultured cells of a vascular endothelium in an environment having a second level of oxygen, the second level of oxygen having a greater oxygen concentration than the first level of oxygen; and

facilitating the flux of oxygen between the first level of oxygen and the second level of oxygen to form a physiologically-relevant oxygen gradient.