A Two-Phage Cocktail Modulates Gut Microbiota Composition and Metabolic Profiles in an Ex Vivo Colon Model

Area of Science:

• Microbiology
• Gastroenterology
• Metabolic Diseases

Background:

• Antibiotic-resistant bacteria and gut dysbiosis are linked to metabolic diseases like obesity.
• Bacteriophage therapy offers a targeted approach to modulate gut microbiota composition.

Purpose of the Study:

• To evaluate the impact of a two-phage cocktail on an ex vivo colonic model of obese microbiota.
• To assess the selectivity of phage therapy against *Enterobacter cloacae* and its effect on overall microbial structure and function.

Main Methods:

• Utilized an ex vivo colonic simulation model with microbiota from obese individuals.
• Enriched microbiota with *Enterobacter cloacae* and applied a two-phage cocktail.
• Conducted microbiological analysis, 16S rRNA gene metabarcoding, and short-chain fatty acid profiling.

Main Results:

• The phage cocktail remained active and effectively reduced *E. cloacae* in enriched microbiota.
• Phage therapy selectively reduced *E. cloacae* without significantly altering dominant genera or overall alpha diversity.
• Significant shifts in beta diversity and region-specific increases in lactic and butyric acids were observed.

Conclusions:

• The study provides ex vivo evidence for selective elimination of *E. cloacae* by phage therapy.
• Phage therapy preserved gut microbiota structure and functionality while targeting specific bacteria.
• Findings support phage therapy as a potential precision tool for gut dysbiosis in metabolic disorders.