A complex human gut microbiome cultured in an anaerobic intestine-on-a-chip.


Journal

Nature biomedical engineering
ISSN: 2157-846X
Titre abrégé: Nat Biomed Eng
Pays: England
ID NLM: 101696896

Informations de publication

Date de publication:
07 2019
Historique:
received: 11 09 2018
accepted: 04 04 2019
pubmed: 16 5 2019
medline: 10 3 2020
entrez: 16 5 2019
Statut: ppublish

Résumé

The diverse bacterial populations that comprise the commensal microbiome of the human intestine play a central role in health and disease. A method that sustains complex microbial communities in direct contact with living human intestinal cells and their overlying mucus layer in vitro would thus enable the investigation of host-microbiome interactions. Here, we show the extended coculture of living human intestinal epithelium with stable communities of aerobic and anaerobic human gut microbiota, using a microfluidic intestine-on-a-chip that permits the control and real-time assessment of physiologically relevant oxygen gradients. When compared to aerobic coculture conditions, the establishment of a transluminal hypoxia gradient in the chip increased intestinal barrier function and sustained a physiologically relevant level of microbial diversity, consisting of over 200 unique operational taxonomic units from 11 different genera and an abundance of obligate anaerobic bacteria, with ratios of Firmicutes and Bacteroidetes similar to those observed in human faeces. The intestine-on-a-chip may serve as a discovery tool for the development of microbiome-related therapeutics, probiotics and nutraceuticals.

Identifiants

pubmed: 31086325
doi: 10.1038/s41551-019-0397-0
pii: 10.1038/s41551-019-0397-0
pmc: PMC6658209
mid: NIHMS1526407
doi:

Substances chimiques

Oxygen S88TT14065

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

520-531

Subventions

Organisme : FDA HHS
ID : HHSF223201310079C
Pays : United States
Organisme : FDA HHS
ID : HHSF223201310079C
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK034854
Pays : United States
Organisme : NIBIB NIH HHS
ID : R01 EB020004
Pays : United States

Commentaires et corrections

Type : CommentIn
Type : ErratumIn
Type : CommentIn

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Auteurs

Sasan Jalili-Firoozinezhad (S)

Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Department of Bioengineering and Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.

Francesca S Gazzaniga (FS)

Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Department of Immunology, Harvard Medical School, Boston, MA, USA.

Elizabeth L Calamari (EL)

Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.

Diogo M Camacho (DM)

Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.

Cicely W Fadel (CW)

Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.

Amir Bein (A)

Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.

Ben Swenor (B)

Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.

Bret Nestor (B)

Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.

Michael J Cronce (MJ)

Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.

Alessio Tovaglieri (A)

Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.

Oren Levy (O)

Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.

Katherine E Gregory (KE)

Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Department of Pediatrics, Harvard Medical School, Boston, MA, USA.

David T Breault (DT)

Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
Department of Endocrinology, Boston Children's Hospital, Boston, MA, USA.
Harvard Stem Cell Institute, Cambridge, MA, USA.

Joaquim M S Cabral (JMS)

Department of Bioengineering and Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.

Dennis L Kasper (DL)

Department of Immunology, Harvard Medical School, Boston, MA, USA.

Richard Novak (R)

Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.

Donald E Ingber (DE)

Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. don.ingber@wyss.harvard.edu.
Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. don.ingber@wyss.harvard.edu.
Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA, USA. don.ingber@wyss.harvard.edu.

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Classifications MeSH