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Harnessing Colon Chip Technology to Identify Commensal Bacteria That Promote Host Tolerance to Infection

Commensal bacteria within the gut microbiome contribute to development of host tolerance to infection, however, identifying specific microbes responsible for this response is difficult. Here we describe methods for developing microfluidic organ-on-a-chip models of small and large intestine lined wit...

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Autores principales: Gazzaniga, Francesca S., Camacho, Diogo M., Wu, Meng, Silva Palazzo, Matheus F., Dinis, Alexandre L. M., Grafton, Francis N., Cartwright, Mark J., Super, Michael, Kasper, Dennis L., Ingber, Donald E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996096/
https://www.ncbi.nlm.nih.gov/pubmed/33777849
http://dx.doi.org/10.3389/fcimb.2021.638014
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author Gazzaniga, Francesca S.
Camacho, Diogo M.
Wu, Meng
Silva Palazzo, Matheus F.
Dinis, Alexandre L. M.
Grafton, Francis N.
Cartwright, Mark J.
Super, Michael
Kasper, Dennis L.
Ingber, Donald E.
author_facet Gazzaniga, Francesca S.
Camacho, Diogo M.
Wu, Meng
Silva Palazzo, Matheus F.
Dinis, Alexandre L. M.
Grafton, Francis N.
Cartwright, Mark J.
Super, Michael
Kasper, Dennis L.
Ingber, Donald E.
author_sort Gazzaniga, Francesca S.
collection PubMed
description Commensal bacteria within the gut microbiome contribute to development of host tolerance to infection, however, identifying specific microbes responsible for this response is difficult. Here we describe methods for developing microfluidic organ-on-a-chip models of small and large intestine lined with epithelial cells isolated from duodenal, jejunal, ileal, or colon organoids derived from wild type or transgenic mice. To focus on host-microbiome interactions, we carried out studies with the mouse Colon Chip and demonstrated that it can support co-culture with living gut microbiome and enable assessment of effects on epithelial adhesion, tight junctions, barrier function, mucus production, and cytokine release. Moreover, infection of the Colon Chips with the pathogenic bacterium, Salmonella typhimurium, resulted in epithelial detachment, decreased tight junction staining, and increased release of chemokines (CXCL1, CXCL2, and CCL20) that closely mimicked changes previously seen in mice. Symbiosis between microbiome bacteria and the intestinal epithelium was also recapitulated by populating Colon Chips with complex living mouse or human microbiome. By taking advantage of differences in the composition between complex microbiome samples cultured on each chip using 16s sequencing, we were able to identify Enterococcus faecium as a positive contributor to host tolerance, confirming past findings obtained in mouse experiments. Thus, mouse Intestine Chips may represent new experimental in vitro platforms for identifying particular bacterial strains that modulate host response to pathogens, as well as for investigating the cellular and molecular basis of host-microbe interactions.
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spelling pubmed-79960962021-03-27 Harnessing Colon Chip Technology to Identify Commensal Bacteria That Promote Host Tolerance to Infection Gazzaniga, Francesca S. Camacho, Diogo M. Wu, Meng Silva Palazzo, Matheus F. Dinis, Alexandre L. M. Grafton, Francis N. Cartwright, Mark J. Super, Michael Kasper, Dennis L. Ingber, Donald E. Front Cell Infect Microbiol Cellular and Infection Microbiology Commensal bacteria within the gut microbiome contribute to development of host tolerance to infection, however, identifying specific microbes responsible for this response is difficult. Here we describe methods for developing microfluidic organ-on-a-chip models of small and large intestine lined with epithelial cells isolated from duodenal, jejunal, ileal, or colon organoids derived from wild type or transgenic mice. To focus on host-microbiome interactions, we carried out studies with the mouse Colon Chip and demonstrated that it can support co-culture with living gut microbiome and enable assessment of effects on epithelial adhesion, tight junctions, barrier function, mucus production, and cytokine release. Moreover, infection of the Colon Chips with the pathogenic bacterium, Salmonella typhimurium, resulted in epithelial detachment, decreased tight junction staining, and increased release of chemokines (CXCL1, CXCL2, and CCL20) that closely mimicked changes previously seen in mice. Symbiosis between microbiome bacteria and the intestinal epithelium was also recapitulated by populating Colon Chips with complex living mouse or human microbiome. By taking advantage of differences in the composition between complex microbiome samples cultured on each chip using 16s sequencing, we were able to identify Enterococcus faecium as a positive contributor to host tolerance, confirming past findings obtained in mouse experiments. Thus, mouse Intestine Chips may represent new experimental in vitro platforms for identifying particular bacterial strains that modulate host response to pathogens, as well as for investigating the cellular and molecular basis of host-microbe interactions. Frontiers Media S.A. 2021-03-12 /pmc/articles/PMC7996096/ /pubmed/33777849 http://dx.doi.org/10.3389/fcimb.2021.638014 Text en Copyright © 2021 Gazzaniga, Camacho, Wu, Silva Palazzo, Dinis, Grafton, Cartwright, Super, Kasper and Ingber http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Gazzaniga, Francesca S.
Camacho, Diogo M.
Wu, Meng
Silva Palazzo, Matheus F.
Dinis, Alexandre L. M.
Grafton, Francis N.
Cartwright, Mark J.
Super, Michael
Kasper, Dennis L.
Ingber, Donald E.
Harnessing Colon Chip Technology to Identify Commensal Bacteria That Promote Host Tolerance to Infection
title Harnessing Colon Chip Technology to Identify Commensal Bacteria That Promote Host Tolerance to Infection
title_full Harnessing Colon Chip Technology to Identify Commensal Bacteria That Promote Host Tolerance to Infection
title_fullStr Harnessing Colon Chip Technology to Identify Commensal Bacteria That Promote Host Tolerance to Infection
title_full_unstemmed Harnessing Colon Chip Technology to Identify Commensal Bacteria That Promote Host Tolerance to Infection
title_short Harnessing Colon Chip Technology to Identify Commensal Bacteria That Promote Host Tolerance to Infection
title_sort harnessing colon chip technology to identify commensal bacteria that promote host tolerance to infection
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996096/
https://www.ncbi.nlm.nih.gov/pubmed/33777849
http://dx.doi.org/10.3389/fcimb.2021.638014
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