| Autor: |
Le HT; Blacktown Clinical School, Western Sydney University, Sydney, Australia.; Storr Liver Centre, Westmead Institute for Medical Research, Sydney, Australia., Lubian AF; Centre for Infectious Diseases and Microbiology (CIDM), Westmead Institute for Medical Research, Sydney, Australia.; Sydney Infectious Diseases Institute, Faculty of Medicine and Health, University of Sydney, Sydney, Australia., Bowring B; Centre for Infectious Diseases and Microbiology (CIDM), Westmead Institute for Medical Research, Sydney, Australia., van der Poorten D; Department of Hepatology and Gastroenterology, Westmead Hospital, Westmead, Australia., Iredell J; Centre for Infectious Diseases and Microbiology (CIDM), Westmead Institute for Medical Research, Sydney, Australia.; Sydney Infectious Diseases Institute, Faculty of Medicine and Health, University of Sydney, Sydney, Australia., George J; Storr Liver Centre, Westmead Institute for Medical Research, Sydney, Australia.; Department of Hepatology and Gastroenterology, Westmead Hospital, Westmead, Australia.; School of Medicine, The University of Sydney, Sydney, Australia., Venturini C; Centre for Infectious Diseases and Microbiology (CIDM), Westmead Institute for Medical Research, Sydney, Australia.; Sydney School of Veterinary Science, The University of Sydney, Sydney, Australia., Ahlenstiel G; Blacktown Clinical School, Western Sydney University, Sydney, Australia.; Storr Liver Centre, Westmead Institute for Medical Research, Sydney, Australia.; Blacktown Mt Druitt Hospital, Sydney, Australia., Read S; Blacktown Clinical School, Western Sydney University, Sydney, Australia.; Storr Liver Centre, Westmead Institute for Medical Research, Sydney, Australia.; Blacktown Mt Druitt Hospital, Sydney, Australia. |
| Abstrakt: |
Bacteriophages (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. |
