Cargando…

Species-specific enhancement of enterohemorrhagic E. coli pathogenesis mediated by microbiome metabolites

BACKGROUND: Species-specific differences in tolerance to infection are exemplified by the high susceptibility of humans to enterohemorrhagic Escherichia coli (EHEC) infection, whereas mice are relatively resistant to this pathogen. This intrinsic species-specific difference in EHEC infection limits...

Descripción completa

Detalles Bibliográficos
Autores principales: Tovaglieri, Alessio, Sontheimer-Phelps, Alexandra, Geirnaert, Annelies, Prantil-Baun, Rachelle, Camacho, Diogo M., Chou, David B., Jalili-Firoozinezhad, Sasan, de Wouters, Tomás, Kasendra, Magdalena, Super, Michael, Cartwright, Mark J., Richmond, Camilla A., Breault, David T., Lacroix, Christophe, Ingber, Donald E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425591/
https://www.ncbi.nlm.nih.gov/pubmed/30890187
http://dx.doi.org/10.1186/s40168-019-0650-5
_version_ 1783404867536027648
author Tovaglieri, Alessio
Sontheimer-Phelps, Alexandra
Geirnaert, Annelies
Prantil-Baun, Rachelle
Camacho, Diogo M.
Chou, David B.
Jalili-Firoozinezhad, Sasan
de Wouters, Tomás
Kasendra, Magdalena
Super, Michael
Cartwright, Mark J.
Richmond, Camilla A.
Breault, David T.
Lacroix, Christophe
Ingber, Donald E.
author_facet Tovaglieri, Alessio
Sontheimer-Phelps, Alexandra
Geirnaert, Annelies
Prantil-Baun, Rachelle
Camacho, Diogo M.
Chou, David B.
Jalili-Firoozinezhad, Sasan
de Wouters, Tomás
Kasendra, Magdalena
Super, Michael
Cartwright, Mark J.
Richmond, Camilla A.
Breault, David T.
Lacroix, Christophe
Ingber, Donald E.
author_sort Tovaglieri, Alessio
collection PubMed
description BACKGROUND: Species-specific differences in tolerance to infection are exemplified by the high susceptibility of humans to enterohemorrhagic Escherichia coli (EHEC) infection, whereas mice are relatively resistant to this pathogen. This intrinsic species-specific difference in EHEC infection limits the translation of murine research to human. Furthermore, studying the mechanisms underlying this differential susceptibility is a difficult problem due to complex in vivo interactions between the host, pathogen, and disparate commensal microbial communities. RESULTS: We utilize organ-on-a-chip (Organ Chip) microfluidic culture technology to model damage of the human colonic epithelium induced by EHEC infection, and show that epithelial injury is greater when exposed to metabolites derived from the human gut microbiome compared to mouse. Using a multi-omics approach, we discovered four human microbiome metabolites—4-methyl benzoic acid, 3,4-dimethylbenzoic acid, hexanoic acid, and heptanoic acid—that are sufficient to mediate this effect. The active human microbiome metabolites preferentially induce expression of flagellin, a bacterial protein associated with motility of EHEC and increased epithelial injury. Thus, the decreased tolerance to infection observed in humans versus other species may be due in part to the presence of compounds produced by the human intestinal microbiome that actively promote bacterial pathogenicity. CONCLUSION: Organ-on-chip technology allowed the identification of specific human microbiome metabolites modulating EHEC pathogenesis. These identified metabolites are sufficient to increase susceptibility to EHEC in our human Colon Chip model and they contribute to species-specific tolerance. This work suggests that higher concentrations of these metabolites could be the reason for higher susceptibility to EHEC infection in certain human populations, such as children. Furthermore, this research lays the foundation for therapeutic-modulation of microbe products in order to prevent and treat human bacterial infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40168-019-0650-5) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-6425591
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-64255912019-03-29 Species-specific enhancement of enterohemorrhagic E. coli pathogenesis mediated by microbiome metabolites Tovaglieri, Alessio Sontheimer-Phelps, Alexandra Geirnaert, Annelies Prantil-Baun, Rachelle Camacho, Diogo M. Chou, David B. Jalili-Firoozinezhad, Sasan de Wouters, Tomás Kasendra, Magdalena Super, Michael Cartwright, Mark J. Richmond, Camilla A. Breault, David T. Lacroix, Christophe Ingber, Donald E. Microbiome Research BACKGROUND: Species-specific differences in tolerance to infection are exemplified by the high susceptibility of humans to enterohemorrhagic Escherichia coli (EHEC) infection, whereas mice are relatively resistant to this pathogen. This intrinsic species-specific difference in EHEC infection limits the translation of murine research to human. Furthermore, studying the mechanisms underlying this differential susceptibility is a difficult problem due to complex in vivo interactions between the host, pathogen, and disparate commensal microbial communities. RESULTS: We utilize organ-on-a-chip (Organ Chip) microfluidic culture technology to model damage of the human colonic epithelium induced by EHEC infection, and show that epithelial injury is greater when exposed to metabolites derived from the human gut microbiome compared to mouse. Using a multi-omics approach, we discovered four human microbiome metabolites—4-methyl benzoic acid, 3,4-dimethylbenzoic acid, hexanoic acid, and heptanoic acid—that are sufficient to mediate this effect. The active human microbiome metabolites preferentially induce expression of flagellin, a bacterial protein associated with motility of EHEC and increased epithelial injury. Thus, the decreased tolerance to infection observed in humans versus other species may be due in part to the presence of compounds produced by the human intestinal microbiome that actively promote bacterial pathogenicity. CONCLUSION: Organ-on-chip technology allowed the identification of specific human microbiome metabolites modulating EHEC pathogenesis. These identified metabolites are sufficient to increase susceptibility to EHEC in our human Colon Chip model and they contribute to species-specific tolerance. This work suggests that higher concentrations of these metabolites could be the reason for higher susceptibility to EHEC infection in certain human populations, such as children. Furthermore, this research lays the foundation for therapeutic-modulation of microbe products in order to prevent and treat human bacterial infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40168-019-0650-5) contains supplementary material, which is available to authorized users. BioMed Central 2019-03-20 /pmc/articles/PMC6425591/ /pubmed/30890187 http://dx.doi.org/10.1186/s40168-019-0650-5 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Tovaglieri, Alessio
Sontheimer-Phelps, Alexandra
Geirnaert, Annelies
Prantil-Baun, Rachelle
Camacho, Diogo M.
Chou, David B.
Jalili-Firoozinezhad, Sasan
de Wouters, Tomás
Kasendra, Magdalena
Super, Michael
Cartwright, Mark J.
Richmond, Camilla A.
Breault, David T.
Lacroix, Christophe
Ingber, Donald E.
Species-specific enhancement of enterohemorrhagic E. coli pathogenesis mediated by microbiome metabolites
title Species-specific enhancement of enterohemorrhagic E. coli pathogenesis mediated by microbiome metabolites
title_full Species-specific enhancement of enterohemorrhagic E. coli pathogenesis mediated by microbiome metabolites
title_fullStr Species-specific enhancement of enterohemorrhagic E. coli pathogenesis mediated by microbiome metabolites
title_full_unstemmed Species-specific enhancement of enterohemorrhagic E. coli pathogenesis mediated by microbiome metabolites
title_short Species-specific enhancement of enterohemorrhagic E. coli pathogenesis mediated by microbiome metabolites
title_sort species-specific enhancement of enterohemorrhagic e. coli pathogenesis mediated by microbiome metabolites
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425591/
https://www.ncbi.nlm.nih.gov/pubmed/30890187
http://dx.doi.org/10.1186/s40168-019-0650-5
work_keys_str_mv AT tovaglierialessio speciesspecificenhancementofenterohemorrhagicecolipathogenesismediatedbymicrobiomemetabolites
AT sontheimerphelpsalexandra speciesspecificenhancementofenterohemorrhagicecolipathogenesismediatedbymicrobiomemetabolites
AT geirnaertannelies speciesspecificenhancementofenterohemorrhagicecolipathogenesismediatedbymicrobiomemetabolites
AT prantilbaunrachelle speciesspecificenhancementofenterohemorrhagicecolipathogenesismediatedbymicrobiomemetabolites
AT camachodiogom speciesspecificenhancementofenterohemorrhagicecolipathogenesismediatedbymicrobiomemetabolites
AT choudavidb speciesspecificenhancementofenterohemorrhagicecolipathogenesismediatedbymicrobiomemetabolites
AT jalilifiroozinezhadsasan speciesspecificenhancementofenterohemorrhagicecolipathogenesismediatedbymicrobiomemetabolites
AT dewouterstomas speciesspecificenhancementofenterohemorrhagicecolipathogenesismediatedbymicrobiomemetabolites
AT kasendramagdalena speciesspecificenhancementofenterohemorrhagicecolipathogenesismediatedbymicrobiomemetabolites
AT supermichael speciesspecificenhancementofenterohemorrhagicecolipathogenesismediatedbymicrobiomemetabolites
AT cartwrightmarkj speciesspecificenhancementofenterohemorrhagicecolipathogenesismediatedbymicrobiomemetabolites
AT richmondcamillaa speciesspecificenhancementofenterohemorrhagicecolipathogenesismediatedbymicrobiomemetabolites
AT breaultdavidt speciesspecificenhancementofenterohemorrhagicecolipathogenesismediatedbymicrobiomemetabolites
AT lacroixchristophe speciesspecificenhancementofenterohemorrhagicecolipathogenesismediatedbymicrobiomemetabolites
AT ingberdonalde speciesspecificenhancementofenterohemorrhagicecolipathogenesismediatedbymicrobiomemetabolites