Using a human colonoid-derived monolayer to study bacteriophage translocation
ABSTRACTBacteriophages (phages) are estimated to be the most abundant microorganisms on Earth. Their presence in human blood suggests that they can translocate from non-sterile sites such as the gastrointestinal tract where they are concentrated. To examine phage translocation ex vivo, we adapted a...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Gut Microbes |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2024.2331520 |
| _version_ | 1797248639671730176 |
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| author | Huu Thanh Le Alicia Fajardo Lubian Bethany Bowring David van der Poorten Jonathan Iredell Jacob George Carola Venturini Golo Ahlenstiel Scott Read |
| author_facet | Huu Thanh Le Alicia Fajardo Lubian Bethany Bowring David van der Poorten Jonathan Iredell Jacob George Carola Venturini Golo Ahlenstiel Scott Read |
| author_sort | Huu Thanh Le |
| collection | DOAJ |
| description | ABSTRACTBacteriophages (phages) are estimated to be the most abundant microorganisms on Earth. Their presence in human blood suggests that they can translocate from non-sterile sites such as the gastrointestinal tract where they are concentrated. To examine phage translocation ex vivo, we adapted a primary colonoid monolayer model possessing cell diversity and architecture, and a thick layer of mucus akin to the colonic environment in vivo. We show that the colonoid monolayer is superior to the Caco-2 cell-line model, possessing intact and organized tight junctions and generating a physiologically relevant mucus layer. We showed, using two different phages, that translocation across the colonoid monolayer was largely absent in differentiated monolayers that express mucus, unlike Caco-2 cultures that expressed little to no mucus. By stimulating mucus production or removing mucus, we further demonstrated the importance of colonic mucus in preventing phage translocation. Finally, we used etiological drivers of gut permeability (alcohol, fat, and inflammatory cytokines) to measure their effects on phage translocation, demonstrating that all three stimuli have the capacity to amplify phage translocation. These findings suggest that phage translocation does occur in vivo but may be largely dependent on colonic mucus, an important insight to consider in future phage applications. |
| first_indexed | 2024-04-24T20:17:47Z |
| format | Article |
| id | doaj.art-bda1b9a33a374c8a997010df6d1993d0 |
| institution | Directory Open Access Journal |
| issn | 1949-0976 1949-0984 |
| language | English |
| last_indexed | 2024-04-24T20:17:47Z |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj.art-bda1b9a33a374c8a997010df6d1993d02024-03-22T14:59:29ZengTaylor & Francis GroupGut Microbes1949-09761949-09842024-12-0116110.1080/19490976.2024.2331520Using a human colonoid-derived monolayer to study bacteriophage translocationHuu Thanh Le0Alicia Fajardo Lubian1Bethany Bowring2David van der Poorten3Jonathan Iredell4Jacob George5Carola Venturini6Golo Ahlenstiel7Scott Read8Blacktown Clinical School, Western Sydney University, Sydney, AustraliaCentre for Infectious Diseases and Microbiology (CIDM), Westmead Institute for Medical Research, Sydney, AustraliaCentre for Infectious Diseases and Microbiology (CIDM), Westmead Institute for Medical Research, Sydney, AustraliaDepartment of Hepatology and Gastroenterology, Westmead Hospital, Westmead, AustraliaCentre for Infectious Diseases and Microbiology (CIDM), Westmead Institute for Medical Research, Sydney, AustraliaStorr Liver Centre, Westmead Institute for Medical Research, Sydney, AustraliaCentre for Infectious Diseases and Microbiology (CIDM), Westmead Institute for Medical Research, Sydney, AustraliaBlacktown Clinical School, Western Sydney University, Sydney, AustraliaBlacktown Clinical School, Western Sydney University, Sydney, AustraliaABSTRACTBacteriophages (phages) are estimated to be the most abundant microorganisms on Earth. Their presence in human blood suggests that they can translocate from non-sterile sites such as the gastrointestinal tract where they are concentrated. To examine phage translocation ex vivo, we adapted a primary colonoid monolayer model possessing cell diversity and architecture, and a thick layer of mucus akin to the colonic environment in vivo. We show that the colonoid monolayer is superior to the Caco-2 cell-line model, possessing intact and organized tight junctions and generating a physiologically relevant mucus layer. We showed, using two different phages, that translocation across the colonoid monolayer was largely absent in differentiated monolayers that express mucus, unlike Caco-2 cultures that expressed little to no mucus. By stimulating mucus production or removing mucus, we further demonstrated the importance of colonic mucus in preventing phage translocation. Finally, we used etiological drivers of gut permeability (alcohol, fat, and inflammatory cytokines) to measure their effects on phage translocation, demonstrating that all three stimuli have the capacity to amplify phage translocation. These findings suggest that phage translocation does occur in vivo but may be largely dependent on colonic mucus, an important insight to consider in future phage applications.https://www.tandfonline.com/doi/10.1080/19490976.2024.2331520Bacteriophagephage therapycolonoidintestinal permeabilitytranslocation |
| spellingShingle | Huu Thanh Le Alicia Fajardo Lubian Bethany Bowring David van der Poorten Jonathan Iredell Jacob George Carola Venturini Golo Ahlenstiel Scott Read Using a human colonoid-derived monolayer to study bacteriophage translocation Gut Microbes Bacteriophage phage therapy colonoid intestinal permeability translocation |
| title | Using a human colonoid-derived monolayer to study bacteriophage translocation |
| title_full | Using a human colonoid-derived monolayer to study bacteriophage translocation |
| title_fullStr | Using a human colonoid-derived monolayer to study bacteriophage translocation |
| title_full_unstemmed | Using a human colonoid-derived monolayer to study bacteriophage translocation |
| title_short | Using a human colonoid-derived monolayer to study bacteriophage translocation |
| title_sort | using a human colonoid derived monolayer to study bacteriophage translocation |
| topic | Bacteriophage phage therapy colonoid intestinal permeability translocation |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2024.2331520 |
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