Characterization of the pathophysiological determinants of diarrheagenic Escherichia coli infection using a challenge model in healthy adults

Els van Hoffen, Annick Mercenier, Karine Vidal, Jalil Benyacoub, Joyce Schloesser*, Alwine Kardinaal, Elly Lucas-van de Bos, Ingrid van Alen, Iris Roggero, Kim Duintjer, Anneke Berendts, Ruud Albers, Michiel Kleerebezem, Sandra ten Bruggencate

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

An experimental human challenge model with an attenuated diarrheagenic Escherichia coli (E. coli) strain has been used in food intervention studies aimed to increase resistance to E. coli infection. This study was designed to refine and expand this challenge model. In a double-blind study, healthy male subjects were orally challenged with 1E10 or 5E10 colony-forming units (CFU) of E. coli strain E1392/75-2A. Three weeks later, subjects were rechallenged with 1E10 CFU of E. coli. Before and after both challenges, clinical symptoms and infection- and immune-related biomarkers were analyzed. Subset analysis was performed on clinically high- and low-responders. Regardless of inoculation dose, the first challenge induced clinical symptoms for 2–3 days. In blood, neutrophils, CRP, CXCL10, and CFA/II-specific IgG were induced, and in feces calprotectin and CFA/II-specific IgA. Despite clinical differences between high- and low-responders, infection and immune biomarkers did not differ. The first inoculation induced protection at the second challenge, with a minor clinical response, and no change in biomarkers. The refined study design resulted in a larger dynamic range of symptoms, and identification of biomarkers induced by a challenge with the attenuated E. coli strain E1392/75-2A, which is of value for future intervention studies. Addition of a second inoculation allows to study the protective response induced by a primary infection. Clinicaltrials.gov registration: NCT02541695 (04/09/2015).

Original languageEnglish
Article number6060
JournalScientific Reports
Volume11
Issue number1
DOIs
Publication statusPublished - 15 Mar 2021

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