title: Bacteriophages Targeting Adherent Invasive Escherichia coli Strains as a Promising New Treatment for Crohn's Disease.
abstract: OBJECTIVE
  Adherent invasive Escherichia coli [AIEC] are abnormally predominant on the ileal mucosa of Crohn's disease [CD] patients. They bind to the CEACAM6 receptor expressed on the surface of epithelial cells. We aimed to assess the potential of bacteriophages, viruses infecting bacteria, to decrease the levels of AIEC bacteria associated with the intestinal mucosa.
  
  
  METHODS
  We combined ex vivo and in vivo experiments with murine and human intestinal samples to quantify the ability of virulent bacteriophages to target the prototype AIEC strain LF82.
  
  
  RESULTS
  We found that three virulent bacteriophages were able to replicate in ileal, caecal and colonic sections and faeces homogenates from murine gut samples colonised with the prototype AIEC strain LF82. A single day of per os treatment with the three bacteriophages cocktail given to LF82-colonised CEABAC10 transgenic mice, expressing the human CEACAM6 receptor for AIEC, decreased significantly the number of AIEC in faeces and in the adherent flora of intestinal sections. In addition, a single dose of the cocktail reduced dextran sodium sulphate-induced colitis symptoms on conventional mice colonised with the strain LF82 over a 2-week period. The cocktail targeted also LF82 bacteria in homogenates of ileal biopsies taken from CD patients.
  
  
  CONCLUSIONS
  These findings demonstrate that bacteriophages are a new treatment option for targeting AIEC in CD patients and represent a strong basis for a clinical trial evaluation.
authors.affiliation: Institut Pasteur, Département de Microbiologie, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, Paris, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Galtier
authors.affiliation: Institut Pasteur, Département de Microbiologie, Paris, France.
authors.forename: Luisa
authors.initials: L
authors.lastname: De Sordi
authors.affiliation: Université Clermont Auvergne, INSERM U1071, USC-INRA 2018, M2iSH, Clermont-Ferrand, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Sivignon
authors.affiliation: Université Clermont Auvergne, INSERM U1071, USC-INRA 2018, M2iSH, Clermont-Ferrand, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: de Vallée
authors.affiliation: Institut Pasteur, Département de Microbiologie, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, Paris, France.|Department of Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Damien
authors.initials: D
authors.lastname: Maura
authors.affiliation: Division de Bactériologie, Communauté d'Universités et d'Etablissements Lille Nord de France, Lille, France.|Lille Inflammation Research International Center, Lille, France.
authors.forename: Christel
authors.initials: C
authors.lastname: Neut
authors.affiliation: Division de Bactériologie, Communauté d'Universités et d'Etablissements Lille Nord de France, Lille, France.|Lille Inflammation Research International Center, Lille, France.
authors.forename: Oumaira
authors.initials: O
authors.lastname: Rahmouni
authors.affiliation: Ferring International Center SA, St-Prex, Switzerland.
authors.forename: Kristin
authors.initials: K
authors.lastname: Wannerberger
authors.affiliation: Université Clermont Auvergne, INSERM U1071, USC-INRA 2018, M2iSH, Clermont-Ferrand, France.
authors.forename: Arlette
authors.initials: A
authors.lastname: Darfeuille-Michaud
authors.affiliation: Lille Inflammation Research International Center, Lille, France.|Service des Maladies de l'Appareil Digestif et de la Nutrition, Hôpital Claude Huriez, Lille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Desreumaux
authors.affiliation: Université Clermont Auvergne, INSERM U1071, USC-INRA 2018, M2iSH, Clermont-Ferrand, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Barnich
authors.affiliation: Institut Pasteur, Département de Microbiologie, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Debarbieux
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001435:Bacteriophages / Q000254:growth & development; D002432:Cecum / Q000382:microbiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000382:microbiology / Q000628:therapy*; D003106:Colon / Q000382:microbiology; D003424:Crohn Disease / Q000382:microbiology* / Q000628:therapy; D004847:Epithelial Cells / Q000378:metabolism; D004926:Escherichia coli / Q000821:virology*; D005243:Feces / Q000382:microbiology; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D007082:Ileum / Q000382:microbiology; D007413:Intestinal Mucosa / Q000166:cytology / Q000382:microbiology*; D051379:Mice; D008822:Mice, Transgenic; D000071059:Phage Therapy
chemical_list: D015703:Antigens, CD; C504117:CEACAM6 protein, human; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins
keywords: Phage therapy; antibiotics; colitis; dysbiosis; microbiota