Bacteriophages Synergize with the Gut Microbial Community To Combat Salmonella

Abstract

ABSTRACT Salmonella infection is one of the main causes of food-borne diarrheal diseases worldwide. Although most Salmonella infections can be cleared without treatment, some cause serious illnesses that require antibiotic treatment. In view of the growing emergence of antibiotic-resistant Salmonella strains, novel treatments are increasingly required. Furthermore, there is a striking paucity of data on how a balanced human gut microbiota responds to Salmonella infection. This study aimed to evaluate whether a balanced gut microbiota protects against Salmonella growth and to compare two antimicrobial approaches for managing Salmonella infection: bacteriophage (phage) treatment and antibiotic treatment. Anaerobically cultivated human intestinal microflora (ACHIM) is a feasible model for the human gut microbiota and naturally inhibits Salmonella infection. By mimicking Salmonella infection in vitro using ACHIM, we observed a large reduction of Salmonella growth by the ACHIM itself. Treatments with phage and antibiotic further inhibited Salmonella growth. However, phage treatment had less impact on the nontargeted bacteria in ACHIM than the antibiotic treatment did. Phage treatment has high specificity when combating Salmonella infection and offers a noninvasive alternative to antibiotic treatment. IMPORTANCE Antibiotic-resistant bacteria are a global threat. Therefore, alternative approaches for combatting bacteria, especially antibiotic-resistant bacteria, are urgently needed. Using a human gut microbiota model, we demonstrate that bacteriophages (phages) are able to substantially decrease pathogenic Salmonella without perturbing the microbiota. Conversely, antibiotic treatment leads to the eradication of close to all commensal bacteria, leaving only antibiotic-resistant bacteria. An unbalanced microbiota has been linked to many diseases both in the gastrointestinal tract or “nonintestinal” diseases. In our study, we show that the microbiota provides a protective effect against Salmonella. Since phage treatment preserves the healthy gut microbiota, it is a feasible superior alternative to antibiotic treatment. Furthermore, when combating infections caused by pathogenic bacteria, gut microbiota should be considered. Author Video: An author video summary of this article is available.

Keywords

• anaerobically cultivated human intestinal microflora (ACHIM)
• microbiota
• Salmonella
• antibiotic resistance
• bacteriophages