In Vitro Investigation of Phage Targeting E. coli K1 in Pregnant Donors' Intestinal Microbiota

Extra-intestinal E. coli (ExPEC) have a high potential for transmission through diet and poultry is the food source that has the strongest association with human ExPEC. Avian pathogenic E. coli (APEC) serogroup O18:K1 share many similarities with those responsible for neonatal meningitis in humans. The asymptomatic carriage of these strains in the maternal intestinal microbiota constitutes a risk of vertical transmission to infant at birth. Phage therapy is a promising alternative to antibiotics and previous work has enabled the selection of the phage vB_EcoP_K1_ULINTec4, active against avian and human O18:K1 strains. This work aimed to evaluate the efficacy of phage therapy against E. coli O18:K1 in an intestinal environment and its impact on the intestinal microbiota. For this purpose, three independent experiments were conducted on the SHIME® system, the first one with only the phage vB_EcoP_K1_ULINTec4, the second experiment with only E. coli K1 and the last experiment with both E. coli K1 and the phage. Microbiota monitoring was performed using metagenetics, qPCR, SCFA analysis and the induction of AhR. The results showed that phage vB_EcoP_K1_ULINTec4, inoculated alone, was progressively cleared by the system and replicates in the presence of its host. E. coli K1 persisted in the microbiota but decreased in the presence of the phage. The impact on the microbiota was revealed to be donor dependent, and the bacterial populations were not dramatically affected by vB_K1_ULINTec4, either alone or with its host. In conclusion, these experiments showed that the phage was able to infect the E. coli K1 in the system but did not completely eliminate the bacterial load.
This research was funded by the Walloon Public Service, BIOWIN (Health Cluster of Wallonia, Belgium) project: Inteliphages.