Phage induced Strain Replacement within Microbiomes

In recent decades, microbiome research has gained increasing relevance in the field of public health. It vastly contributed to understanding the pathogenesis of major non-communicable human diseases but also generated knowledge on the emergence and spread of antibiotic resistant bacteria (ABR). One crucial forthcoming task involves formulating strategies for microbiome editing, specifically targeting the elimination of harmful or antibiotic-resistant bacteria from the human gut. The objective is to achieve this without compromising or disturbing the overall composition of the microbiota.

To address this question, we focus on a new strategy termed "phage induced strain replacement within microbiomes", which aims at combining phage- and probiotics-based therapy within one treatment. This approach is grounded in previous observations made in gnotobiotic mice colonized with the Oligo-MM12 synthetic bacterial community (Von Strempel et al. 2022; Brugiroux et al. 2016). We aim at posing a fitness disadvantage on the targeted strain by a strain-specific phage cocktail while introducing a second, closely related, but phage-resistant niche competitor at the same time. Ideally, this approach leads to strain replacement and elimination of the targeted strain without disturbing the overall gut microbiota composition. We focus on the three species Escherichia coli, Enterococcus faecalis and Phocaeicola vulgatus (formerly Bacteroides vulgatus). We confirmed our theory in batch culture setups showing that phage induced strain replacement is possible. Presently, we are building phage and competitor strain libraries for E. faecalis. These will be utilized in subsequent experiments conducted under various environmental conditions, both in vitro and in vivo. The aim is to further assess the potential efficacy of strain replacement as a novel therapeutic approach for addressing antibiotic resistance (ABR) and chronic intestinal diseases.