Escherichia coli K1 is a leading cause of neonatal meningitis. The asymptomatic carriage of these strains in the maternal intestinal microbiota constitutes a risk of vertical transmission to the infant at birth. The aim of this work was to evaluate the efficacy of phage therapy against E. coli 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.

Functional symbiotic intestinal microbiota regulates immune defense and the metabolic processing of xenobiotics in the host. The aryl hydrocarbon receptor (AhR) is one of the transcription factors mediating host–microbe interaction. An in vitro static simulation of the human colon was used in this work to analyze the evolution of bacterial populations, the microbial metabolic output, and the potential induction of AhR transcriptional activity in healthy gut ecosystems. Fifteen target taxa were explored by qPCR, and the metabolic content was chromatographically profiled using SPME-GC-MS and UPLC-FLD to quantify short-chain fatty acids (SCFA) and biogenic amines, respectively. Over 72 h of fermentation, the microbiota and most produced metabolites remained stable. Fermentation supernatant induced AhR transcription in two of the three reporter gene cell lines (T47D, HepG2, HT29) evaluated. Mammary and intestinal cells were more sensitive to microbiota metabolic production, which showed greater AhR agonism than the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) used as a positive control. Some of the SCFA and biogenic amines identified could crucially contribute to the potent AhR induction of the fermentation products. As a fundamental pathway mediating human intestinal homeostasis and as a sensor for several microbial metabolites, AhR activation might be a useful endpoint to include in studies of the gut microbiota.

New control methods are needed to counter antimicrobial resistances and the use of bacteriophages as an alternative treatment seems promising. To that end, the effect of the phage vB_KpnP_K1-ULIP33, whose host is the hypervirulent Klebsiella pneumoniae SA12 (ST23 and capsular type K1), was assessed on intestinal microbiota, using an in vitro model: the SHIME^® system (Simulator of the Human Intestinal Microbial Ecosystem). After stabilization of the system, the phage was inoculated for 7 days and its persistence in the different colons was studied until its disappearance from the system. The concentration of short chain fatty acids in the colons showed good colonization of the bioreactors by the microbiota and no significant effect related to the phage treatment. Diversity (α and β), the relative abundance of bacteria, and qPCR analysis targeting different genera of interest showed no significant variation following phage administration. Even if further in vitro studies are needed to assess the efficacy of this phage against its bacterial host within the human intestinal ecosystem, the phage ULIP33 exerted no significant change on the global colonic microbiota.