Engineering novel enteroid models for understanding human enteric disease
Inventors
Fofanova, Tatiana Y. • Auchtung, Jennifer • Wilson, Reid Laurence • Stewart, Christopher • PETROSINO, JOSEPH • Britton, Robert Allen • Grande-Allen, Jane • Shroyer, Noah F. • Estes, Mary K.
Assignees
Baylor College of Medicine • William Marsh Rice University
Publication Number
US-12337311-B2
Publication Date
2025-06-24
Expiration Date
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Abstract
An anaerobic chamber system to evaluate human enteric disease is described herein that can be used to test therapeutic components. In specific embodiments, the anaerobic chamber is used to determine the effect of one or more bacterial communities on ex vivo enteroid cultures. In one application, the anaerobic chamber system is used to determine the efficacy of therapeutic components in ameliorating human enteric disease using personalized medicine.
Core Innovation
An anaerobic chamber system to evaluate human enteric disease is described that can be used to test therapeutic components, and in specific embodiments the anaerobic chamber is used to determine the effect of one or more bacterial communities on ex vivo enteroid cultures and to determine the efficacy of therapeutic components in ameliorating human enteric disease using personalized medicine.
Mechanistic investigations of host-microbe interactions in the human gut are limited because the intestinal epithelium is oxygen-dependent while most gut bacteria are obligate anaerobes, creating an exceptionally steep oxygen gradient across the single-cell-thick epithelial layer, and because the intestinal epithelium is in a state of chronic low-grade hypoxia that standard cell culture incubators do not replicate; by failing to perform studies under physiologically relevant oxygen concentrations, unreliable results may be produced.
The disclosure provides systems, methods, and compositions that allow physiologically relevant co-culture of anaerobic microbes with gut tissues, including enteroids, by using an Enteroid-Anaerobe Co-Culture (EACC) system and related assemblies comprising an anaerobic chamber, an aerobic chamber, and a gas adjustable chamber configured to provide physiologically relevant oxygen control to recapitulate the phenotype and response of a host.
Claims Coverage
The independent claim recites a multi-chamber co-culture system with the following main inventive features (6 features identified).
Multi-chamber co-culture system
A co-culture system for co-culturing anaerobic microbes and gut tissue comprising two or more anaerobic chambers and two or more aerobic chambers, and a gas adjustable chamber comprising a gas.
Removably insertable anaerobic chambers
Each anaerobic chamber is removably insertable into a single aerobic chamber.
Gas permeable base comprising gut tissue
Each anaerobic chamber comprises a gas permeable base, wherein the gas permeable base comprises gut tissue of a subject in the anaerobic chamber.
Apical anaerobic and basolateral oxygenated configuration
The gut tissue comprises an apical side and a basolateral side; the apical side faces the anaerobic chamber and is anaerobic while the basolateral side is oxygenated.
Gaseous communication between chambers via gas permeable bases
When a single anaerobic chamber is inserted into the single aerobic chamber, the single anaerobic chamber is gaseously communicable with the single aerobic chamber.
Shared gas permeable side to gas adjustable chamber
There is a gas permeable side common to the two or more aerobic chambers and the gas adjustable chamber.
The independent claim covers a multi-level co-culture apparatus that spatially separates an anaerobic apical compartment and an oxygenated basolateral compartment using gas-permeable interfaces and removable chambers, and further defines shared gas-permeable communication to a gas adjustable chamber.
Stated Advantages
Allows physiologically relevant co-culture of anaerobic microbes with gut tissues, including enteroids.
Provides a simple, cost-effective method for co-culturing microbes with gut tissues under variable oxygen conditions.
Enables testing of therapeutic components and determination of efficacy of therapies ex vivo, including personalized medicine applications.
Facilitates drug discovery in an environment that closely mimics the gut in vivo and permits pre-clinical validation of microbial therapeutic efficacy.
Reduces experimental error and improves reproducibility to more accurately inform downstream in vivo studies.
Documented Applications
Testing therapeutic components and determining the efficacy of one or more therapies for medical conditions ex vivo using enteroid cultures and microbes.
Determining the effect of one or more bacterial communities on ex vivo enteroid cultures.
Drug discovery and pre-clinical validation of microbial therapeutics in an environment that mimics the gut in vivo, including bacteriotherapy evaluation.
Personalized medicine methods comprising exposing one or more therapies to the system where the gut tissue is from the subject to determine a suitable therapy for that subject.
Research, diagnostic, and therapy identification purposes including identifying host-microbe relationships, assessing methods or compositions that affect host-microbe interaction, and detection of genetic profiles related to enteric disease.
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