TY - JOUR
T1 - Investigating the survival and activity of a bacteriophage in the complex colon environment with the use of a dynamic model of the colon (TIM-2)
AU - Maas, E.
AU - Penders, J.
AU - Venema, K.
N1 - Funding Information:
This research was funded by the Center of Healthy Eating & Food Innovation (HEFI) of Maastricht University – Campus Venlo and has been made possible with the support by the Province of Limburg.
Publisher Copyright:
© 2023
PY - 2023/5/1
Y1 - 2023/5/1
N2 - The rise of antibiotic resistance poses a global problem. To avoid this, alternative therapeutic options should be explored, e.g. lytic bacteriophage therapy. Well-designed and described research on effectivity of oral bacte-riophage therapy is lacking, therefore the aim of this study was to determine whether the in vitro model of the colon (TIM-2) could be used to investigate the survival and efficacy of therapeutic bacteriophages. For this, an antibiotic-resistant (CmR) E. coli DH5 alpha(pGK11) was used in combination with a corresponding bacteriophage. For the survival study, the TIM-2 model was inoculated with the microbiota of healthy individuals and a standard feeding (SIEM) was fed over the course of the 72 h experiment. To test the bacteriophage, different interventions were carried out. Survival of bacteriophages and bacteria was followed by plating of the lumen samples at different time points 0, 2, 4, 8, 24, 48, and 72 h. In addition, the stability of the bacterial community was determined with the use of 16S rRNA sequencing. Results showed that the phage titers could be decreased by activity from the commensal microbiota. Levels of the phage host (here E.coli) were decreased in the in-terventions with the phage shot. Multiple shots did not seem to be more effective than a single shot. At the same time, the bacterial community was not disturbed and remained stable throughout the experiment, which is in stark contrast to treatment with antibiotics. Mechanistic studies such as this one are required to optimize efficacy of phage therapy.
AB - The rise of antibiotic resistance poses a global problem. To avoid this, alternative therapeutic options should be explored, e.g. lytic bacteriophage therapy. Well-designed and described research on effectivity of oral bacte-riophage therapy is lacking, therefore the aim of this study was to determine whether the in vitro model of the colon (TIM-2) could be used to investigate the survival and efficacy of therapeutic bacteriophages. For this, an antibiotic-resistant (CmR) E. coli DH5 alpha(pGK11) was used in combination with a corresponding bacteriophage. For the survival study, the TIM-2 model was inoculated with the microbiota of healthy individuals and a standard feeding (SIEM) was fed over the course of the 72 h experiment. To test the bacteriophage, different interventions were carried out. Survival of bacteriophages and bacteria was followed by plating of the lumen samples at different time points 0, 2, 4, 8, 24, 48, and 72 h. In addition, the stability of the bacterial community was determined with the use of 16S rRNA sequencing. Results showed that the phage titers could be decreased by activity from the commensal microbiota. Levels of the phage host (here E.coli) were decreased in the in-terventions with the phage shot. Multiple shots did not seem to be more effective than a single shot. At the same time, the bacterial community was not disturbed and remained stable throughout the experiment, which is in stark contrast to treatment with antibiotics. Mechanistic studies such as this one are required to optimize efficacy of phage therapy.
KW - Bacteriophage
KW - Gut microbiota
KW - E
KW - coli
KW - In vitro colon model
KW - Phage therapy
KW - DISCOVERY
KW - SYSTEM
U2 - 10.1016/j.micpath.2023.106061
DO - 10.1016/j.micpath.2023.106061
M3 - Article
C2 - 36906154
SN - 0882-4010
VL - 178
JO - Microbial Pathogenesis
JF - Microbial Pathogenesis
M1 - 106061
ER -