title: Extensive Modulation of the Fecal Metagenome in Children With Crohn's Disease During Exclusive Enteral Nutrition.
abstract: OBJECTIVE
  Exploring associations between the gut microbiota and colonic inflammation and assessing sequential changes during exclusive enteral nutrition (EEN) may offer clues into the microbial origins of Crohn's disease (CD).
  
  
  METHODS
  Fecal samples (n=117) were collected from 23 CD and 21 healthy children. From CD children fecal samples were collected before, during EEN, and when patients returned to their habitual diets. Microbiota composition and functional capacity were characterized using sequencing of the 16S rRNA gene and shotgun metagenomics.
  
  
  RESULTS
  Microbial diversity was lower in CD than controls before EEN (P=0.006); differences were observed in 36 genera, 141 operational taxonomic units (OTUs), and 44 oligotypes. During EEN, the microbial diversity of CD children further decreased, and the community structure became even more dissimilar than that of controls. Every 10 days on EEN, 0.6 genus diversity equivalents were lost; 34 genera decreased and one increased during EEN. Fecal calprotectin correlated with 35 OTUs, 14 of which accounted for 78% of its variation. OTUs that correlated positively or negatively with calprotectin decreased during EEN. The microbiota of CD patients had a broader functional capacity than healthy controls, but diversity decreased with EEN. Genes involved in membrane transport, sulfur reduction, and nutrient biosynthesis differed between patients and controls. The abundance of genes involved in biotin (P=0.005) and thiamine biosynthesis decreased (P=0.017), whereas those involved in spermidine/putrescine biosynthesis (P=0.031), or the shikimate pathway (P=0.058), increased during EEN.
  
  
  CONCLUSIONS
  Disease improvement following treatment with EEN is associated with extensive modulation of the gut microbiome.
authors.affiliation: Warwick Medical School, University of Warwick, Warwick, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Quince
authors.affiliation: School of Engineering, University of Glasgow, Glasgow, UK.
authors.forename: Umer Zeeshan
authors.initials: UZ
authors.lastname: Ijaz
authors.affiliation: Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK.
authors.forename: Nick
authors.initials: N
authors.lastname: Loman
authors.affiliation: Josephine Bay Paul Center for Comparative Molecular Biology and Evolution, Marine Biological Laboratory, Woods Hole, Massachusetts, USA.
authors.forename: A Murat
authors.initials: AM
authors.lastname: Eren
authors.affiliation: Department of Gastrointestinal Microbiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee, Nuthetal, Germany.
authors.forename: Delphine
authors.initials: D
authors.lastname: Saulnier
authors.affiliation: School of Engineering, University of Glasgow, Glasgow, UK.
authors.forename: Julie
authors.initials: J
authors.lastname: Russell
authors.affiliation: School of Engineering, University of Glasgow, Glasgow, UK.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Haig
authors.affiliation: Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK.
authors.forename: Szymon T
authors.initials: ST
authors.lastname: Calus
authors.affiliation: Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK.
authors.forename: Joshua
authors.initials: J
authors.lastname: Quick
authors.affiliation: Department of Paediatric Gastroenterology, Hepatology and Nutrition, Royal Hospital for Children, Glasgow, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Barclay
authors.affiliation: Department of Gastrointestinal Microbiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee, Nuthetal, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Bertz
authors.affiliation: Department of Gastrointestinal Microbiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee, Nuthetal, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Blaut
authors.affiliation: Department of Paediatric Gastroenterology, Hepatology and Nutrition, Royal Hospital for Children, Glasgow, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Hansen
authors.affiliation: Department of Paediatric Gastroenterology, Hepatology and Nutrition, Royal Hospital for Children, Glasgow, UK.
authors.forename: Paraic
authors.initials: P
authors.lastname: McGrogan
authors.affiliation: Department of Paediatric Gastroenterology, Hepatology and Nutrition, Royal Hospital for Children, Glasgow, UK.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Russell
authors.affiliation: Human Nutrition, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow Royal Infirmary, Glasgow, UK.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Edwards
authors.affiliation: Human Nutrition, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow Royal Infirmary, Glasgow, UK.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Gerasimidis
mesh_terms: D000293:Adolescent; D002648:Child; D003424:Crohn Disease / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology*; D004750:Enteral Nutrition; D005243:Feces / Q000737:chemistry; D005260:Female; D006801:Humans; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism; D016014:Linear Models; D008297:Male; D054892:Metagenome; D056186:Metagenomics / Q000379:methods; D064307:Microbiota / Q000235:genetics; D012336:RNA, Ribosomal, 16S; D017423:Sequence Analysis, RNA
chemical_list: D039841:Leukocyte L1 Antigen Complex; D012336:RNA, Ribosomal, 16S