title: Oral application of Escherichia coli bacteriophage: safety tests in healthy and diarrheal children from Bangladesh.
abstract: A T4-like coliphage cocktail was given with different oral doses to healthy Bangladeshi children in a placebo-controlled randomized phase I safety trial. Fecal phage detection was oral dose dependent suggesting passive gut transit of coliphages through the gut. No adverse effects of phage application were seen clinically and by clinical chemistry. Similar results were obtained for a commercial phage preparation (Coliproteus from Microgen/Russia). By 16S rRNA gene sequencing, only a low degree of fecal microbiota conservation was seen in healthy children from Bangladesh who were sampled over a time interval of 7 days suggesting a substantial temporal fluctuation of the fecal microbiota composition. Microbiota variability was not associated with the age of the children or the presence of phage in the stool. Stool microbiota composition of Bangladeshi children resembled that found in children of other regions of the world. Marked variability in fecal microbiota composition was also seen in 71 pediatric diarrhea patients receiving only oral rehydration therapy and in 38 patients receiving coliphage preparations or placebo when sampled 1.2 or 4 days apart respectively. Temporal stability of the gut microbiota should be assessed in case-control studies involving children before associating fecal microbiota composition with health or disease phenotypes.
authors.affiliation: International Centre for Diarrheal Diseases Research, Bangladesh (icddr,b), Clinical Sciences Division, 68 Shaheed Tajuddin Ahmed Sharani, Mohakhali, Dhaka, 1212, Bangladesh.
authors.forename: Shafiqul Alam
authors.initials: SA
authors.lastname: Sarker
authors.affiliation: Nutrition Health Research, Nestlé Research Centre, Nestec Ltd, Vers-chez-les-Blanc, Lausanne, 26 CH-1000, Switzerland.
authors.forename: Bernard
authors.initials: B
authors.lastname: Berger
authors.affiliation: Nutrition Health Research, Nestlé Research Centre, Nestec Ltd, Vers-chez-les-Blanc, Lausanne, 26 CH-1000, Switzerland.
authors.forename: Ying
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Nutrition Health Research, Nestlé Research Centre, Nestec Ltd, Vers-chez-les-Blanc, Lausanne, 26 CH-1000, Switzerland.
authors.forename: Silas
authors.initials: S
authors.lastname: Kieser
authors.affiliation: Nutrition Health Research, Nestlé Research Centre, Nestec Ltd, Vers-chez-les-Blanc, Lausanne, 26 CH-1000, Switzerland.
authors.forename: Francis
authors.initials: F
authors.lastname: Foata
authors.affiliation: Nestlé Institute of Health Sciences, EPFL Innovation Park, Functional Genomics Group, CH-1015 Lausanne, Switzerland.
authors.forename: Deborah
authors.initials: D
authors.lastname: Moine
authors.affiliation: Nestlé Institute of Health Sciences, EPFL Innovation Park, Functional Genomics Group, CH-1015 Lausanne, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Descombes
authors.affiliation: International Centre for Diarrheal Diseases Research, Bangladesh (icddr,b), Clinical Sciences Division, 68 Shaheed Tajuddin Ahmed Sharani, Mohakhali, Dhaka, 1212, Bangladesh.
authors.forename: Shamima
authors.initials: S
authors.lastname: Sultana
authors.affiliation: International Centre for Diarrheal Diseases Research, Bangladesh (icddr,b), Clinical Sciences Division, 68 Shaheed Tajuddin Ahmed Sharani, Mohakhali, Dhaka, 1212, Bangladesh.
authors.forename: Sayeeda
authors.initials: S
authors.lastname: Huq
authors.affiliation: International Centre for Diarrheal Diseases Research, Bangladesh (icddr,b), Clinical Sciences Division, 68 Shaheed Tajuddin Ahmed Sharani, Mohakhali, Dhaka, 1212, Bangladesh.
authors.forename: Pradip Kumar
authors.initials: PK
authors.lastname: Bardhan
authors.affiliation: Nutrition Health Research, Nestlé Research Centre, Nestec Ltd, Vers-chez-les-Blanc, Lausanne, 26 CH-1000, Switzerland.
authors.forename: Valérie
authors.initials: V
authors.lastname: Vuillet
authors.affiliation: Nutrition Health Research, Nestlé Research Centre, Nestec Ltd, Vers-chez-les-Blanc, Lausanne, 26 CH-1000, Switzerland.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Praplan
authors.affiliation: Nutrition Health Research, Nestlé Research Centre, Nestec Ltd, Vers-chez-les-Blanc, Lausanne, 26 CH-1000, Switzerland.
authors.forename: Harald
authors.initials: H
authors.lastname: Brüssow
mesh_terms: D001435:Bacteriophages / Q000502:physiology*; D001459:Bangladesh; D001691:Biological Therapy / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D003967:Diarrhea / Q000382:microbiology / Q000628:therapy*; D004926:Escherichia coli / Q000502:physiology / Q000821:virology*; D004927:Escherichia coli Infections / Q000382:microbiology / Q000628:therapy*; D005243:Feces / Q000382:microbiology / Q000821:virology; D005260:Female; D006801:Humans; D008297:Male; D012336:RNA, Ribosomal, 16S
chemical_list: D012336:RNA, Ribosomal, 16S