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Updated: Sep 23, 2025
Author Spotlight: Investigating Bacteriophage-Induced Immune Responses in Gnotobiotic Mice
Published on: January 26, 2024
Bacteriophage Cocktail and Microcin-Producing Probiotic Escherichia coli Protect Mice Against Gut Colonization With
Stephen B Porter1, Brian D Johnston2, Dagmara Kisiela3
1Minneapolis VA Health Care System, Veterans Health Administration, United States Department of Veterans Affairs, Minneapolis, MN, United States.
Abstract:
Non-antibiotic measures are needed to reduce the rate of infections due to multidrug-resistant organisms (MDROs), including by eliminating the commensal reservoir that underlies such strains' dissemination and leads to recurrent infections. Here, we tested a cocktail of pre-selected bacteriophages and an engineered microcin C7-producing probiotic Escherichia coli Nissle-1917 strain for their ability to reduce gut colonization by an E. coli strain from sequence type 131 (ST131)-H30R, which is the major clonal group of MDROs among extraintestinal clinical E. coli isolates. Although the bacteriophage cocktail was highly effective against ST131-H30R strains both in vitro and in a murine model of subcutaneous sepsis, it was only weakly and transiently effective against gut colonization by the target ST131-H30R strain (0.5 log10 decrease on d + 1: p < 0.001; no significant effect on d + 4 and beyond). The probiotic strain, while also highly active against ST131-H30R in vitro, was ineffective against ST131-H30R gut colonization despite its abundant presence in feces. Nonetheless, despite failing as decolonizing agents when administered separately, when co-administered the bacteriophage cocktail and probiotic strain exhibited striking synergy against ST131-H30R gut colonization. This combinatory effect was most pronounced on d + 1 (3.3 log10 target strain decrease: p < 0.001), and persisted until d + 7 (0.5 log10 decrease; p < 0.02.). Although by d + 10 the ST131-H30R load was fully restored, these findings provide proof of concept for combined bacteriophage-plus-probiotic administration to reduce or, possibly, to prevent gut colonization with MDROs in high-risk individuals.
Insights
A combination of bacteriophages and a probiotic effectively reduced gut colonization by multidrug-resistant organisms (MDROs). This synergistic approach shows promise for preventing MDRO infections in high-risk individuals.
Area of Science:
- Microbiology
- Infectious Diseases
- Bacteriophage Therapy
Background:
- Multidrug-resistant organisms (MDROs) pose a significant threat, necessitating non-antibiotic interventions.
- Eliminating the gut commensal reservoir of MDROs is crucial for preventing dissemination and recurrent infections.
- Escherichia coli sequence type 131 (ST131)-H30R is a major multidrug-resistant clonal group causing extraintestinal infections.
Purpose of the Study:
- To evaluate the efficacy of a bacteriophage cocktail and a microcin C7-producing probiotic Escherichia coli Nissle-1917 strain in reducing gut colonization by ST131-H30R.
- To investigate the synergistic potential of combining bacteriophages and probiotics against MDRO gut colonization.
Main Methods:
- In vitro and murine models were used to assess the efficacy of bacteriophages and probiotics separately and in combination.
- Gut colonization by a specific ST131-H30R strain was monitored in mice following treatment.
- The reduction in bacterial load was quantified using logarithmic scales (log10).
Main Results:
- The bacteriophage cocktail showed high efficacy against ST131-H30R in vitro and in a sepsis model but had limited, transient effects on gut colonization.
- The probiotic strain was ineffective in reducing ST131-H30R gut colonization despite its presence in feces.
- Co-administration of bacteriophages and probiotics demonstrated significant synergistic effects, reducing ST131-H30R colonization substantially and persistently.
Conclusions:
- While individual treatments showed limited success, the combined bacteriophage-probiotic approach proved highly effective in reducing MDRO gut colonization.
- This study provides proof of concept for using combined bacteriophage-probiotic therapy to manage MDROs in high-risk populations.
- Further research may explore the potential of this strategy for preventing MDRO colonization and subsequent infections.
