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

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,...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/eed09261907148fd8249007c79203b92
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:eed09261907148fd8249007c79203b92
record_format	dspace
spelling	oai:doaj.org-article:eed09261907148fd8249007c79203b922021-12-02T16:31:14ZCharacterization of the pathophysiological determinants of diarrheagenic Escherichia coli infection using a challenge model in healthy adults10.1038/s41598-021-85161-12045-2322https://doaj.org/article/eed09261907148fd8249007c79203b922021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85161-1https://doaj.org/toc/2045-2322Abstract 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).Els van HoffenAnnick MercenierKarine VidalJalil BenyacoubJoyce SchloesserAlwine KardinaalElly Lucas-van de BosIngrid van AlenIris RoggeroKim DuintjerAnneke BerendtsRuud AlbersMichiel KleerebezemSandra ten BruggencateNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 Characterization of the pathophysiological determinants of diarrheagenic Escherichia coli infection using a challenge model in healthy adults
description	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).
format	article
author	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
author_facet	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
author_sort	Els van Hoffen
title	Characterization of the pathophysiological determinants of diarrheagenic Escherichia coli infection using a challenge model in healthy adults
title_short	Characterization of the pathophysiological determinants of diarrheagenic Escherichia coli infection using a challenge model in healthy adults
title_full	Characterization of the pathophysiological determinants of diarrheagenic Escherichia coli infection using a challenge model in healthy adults
title_fullStr	Characterization of the pathophysiological determinants of diarrheagenic Escherichia coli infection using a challenge model in healthy adults
title_full_unstemmed	Characterization of the pathophysiological determinants of diarrheagenic Escherichia coli infection using a challenge model in healthy adults
title_sort	characterization of the pathophysiological determinants of diarrheagenic escherichia coli infection using a challenge model in healthy adults
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/eed09261907148fd8249007c79203b92
work_keys_str_mv	AT elsvanhoffen characterizationofthepathophysiologicaldeterminantsofdiarrheagenicescherichiacoliinfectionusingachallengemodelinhealthyadults AT annickmercenier characterizationofthepathophysiologicaldeterminantsofdiarrheagenicescherichiacoliinfectionusingachallengemodelinhealthyadults AT karinevidal characterizationofthepathophysiologicaldeterminantsofdiarrheagenicescherichiacoliinfectionusingachallengemodelinhealthyadults AT jalilbenyacoub characterizationofthepathophysiologicaldeterminantsofdiarrheagenicescherichiacoliinfectionusingachallengemodelinhealthyadults AT joyceschloesser characterizationofthepathophysiologicaldeterminantsofdiarrheagenicescherichiacoliinfectionusingachallengemodelinhealthyadults AT alwinekardinaal characterizationofthepathophysiologicaldeterminantsofdiarrheagenicescherichiacoliinfectionusingachallengemodelinhealthyadults AT ellylucasvandebos characterizationofthepathophysiologicaldeterminantsofdiarrheagenicescherichiacoliinfectionusingachallengemodelinhealthyadults AT ingridvanalen characterizationofthepathophysiologicaldeterminantsofdiarrheagenicescherichiacoliinfectionusingachallengemodelinhealthyadults AT irisroggero characterizationofthepathophysiologicaldeterminantsofdiarrheagenicescherichiacoliinfectionusingachallengemodelinhealthyadults AT kimduintjer characterizationofthepathophysiologicaldeterminantsofdiarrheagenicescherichiacoliinfectionusingachallengemodelinhealthyadults AT annekeberendts characterizationofthepathophysiologicaldeterminantsofdiarrheagenicescherichiacoliinfectionusingachallengemodelinhealthyadults AT ruudalbers characterizationofthepathophysiologicaldeterminantsofdiarrheagenicescherichiacoliinfectionusingachallengemodelinhealthyadults AT michielkleerebezem characterizationofthepathophysiologicaldeterminantsofdiarrheagenicescherichiacoliinfectionusingachallengemodelinhealthyadults AT sandratenbruggencate characterizationofthepathophysiologicaldeterminantsofdiarrheagenicescherichiacoliinfectionusingachallengemodelinhealthyadults
_version_	1718383907215245312

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

Ejemplares similares