<p>Inflammatory bowel diseases affect ever-increasing numbers of individuals worldwide. Alterations of the intestinal microbiome were reported for Crohn’s disease and at relapse in Ulcerative Colitis (UC); they were not clearly detected in UC at remission. Here we report the characterization of the microbiome by quantitative metagenomics in a cohort of 121 individuals, composed of 65 UC adult patients in remission and 56 healthy controls. A cross-sectional comparison revealed substantial microbiome differences, patients in remission having lower microbiome richness and paucity of the Ruminococcus species driven enterotype. The observed microbiome alterations allowed robust classification of patients by intestinal species abundance, yielding an area under the curve (AUC) of 0.87 in a Receiver-Operator Characteristic (ROC) analysis. Loss of richness was linked to an aggressive UC phenotype and to the importance of past relapses; it was associated with a worse IBD quality of life score (IBDQ-36). Unexpectedly, onset of inflammatory bouts, as assessed by white blood cell count and fecal calprotectin levels, was associated with higher richness; in a longitudinal study of patients at high risk of disease flare, we observed a link between increasing gut microbiome richness over time and calprotectin level, in turn related to clinical inflammatory response and relapse.</p>

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Fecal microbiome of patients with ulcerative colitis reflects their phenotype and inflammatory level

  • Nicolas Maziers,
  • Emmanuelle Le Chatelier,
  • Florian Plaza Oñate,
  • Sébastien Fromentin,
  • Florence Thirion,
  • Nicolas Pons,
  • Natalia Borruel,
  • Francesc Casellas,
  • Antonio Torrejon,
  • Virginia Robles-Alonso,
  • Chaysavanh Manichanh,
  • Encarna Varela,
  • Muriel Derrien,
  • Patrick Veiga,
  • Raish Oozeer,
  • Shinichi Sunagawa,
  • Vincent Lombard,
  • Nicolas Terrapon,
  • Bernard Henrissat,
  • Mathieu Almeida,
  • Maria Antolin,
  • François Artiguenave,
  • Manimozhiyan Arumugam,
  • Jean-Michel Batto,
  • Marcelo Bertalan,
  • Hervé Blottière,
  • Peer Bork,
  • Christian Brechot,
  • Thomas Bruls,
  • Søren Brunak,
  • Kristoffer S. Burgdorf,
  • Paul Igor Costea,
  • Antonella Cultrone,
  • Willem M. de Vos,
  • Christine Delorme,
  • Gérard Denariaz,
  • Rozenn Dervyn,
  • Doré Doré,
  • Gwen Falony,
  • Qiang Feng,
  • Kristoffer Forslund,
  • Niels Grapup,
  • Eric Guedon,
  • Valborg Gudmundsdottir,
  • Florence Haimet,
  • Torben Hansen,
  • Rajna Hercog,
  • Falk Hildebrand,
  • Alexandre Jamet,
  • Torben Jørgensen,
  • Agnieska S. Junker,
  • Catherine Juste,
  • Ghalia Khaci,
  • Sean Kennedy,
  • Michiel Kleerebezem,
  • Jan Knoll,
  • Karsten Kristiansen,
  • Jens Roat Kultima,
  • Séverine Layec,
  • Denis Le Paslier,
  • Marion Leclerc,
  • Pierre Leonard,
  • Florence Levenez,
  • Junhua Li,
  • Christine M’Rini,
  • Emmanuelle Maguin,
  • Daniel R. Mende,
  • Alexandre Mérieux,
  • Trine Nielsen,
  • Henrik Bjørn Nielsen,
  • Julian Parkhill,
  • Helle Krogh Pedersen,
  • Oluf Pedersen,
  • Eric Pelletier,
  • Edi Prifti,
  • Junjie Qin,
  • Jeroen Raes,
  • Simon Rasmussen,
  • Pierre Renault,
  • Maria Rescigno,
  • Nicolas Sanchez,
  • Thomas Sicheritz-Ponten,
  • Julien Tap,
  • Sebastian Tims,
  • Keith Turner,
  • Maarten van de Guchte,
  • Johan E. T. van Hylckama Vlieg,
  • Gaetana Vandemeulebrouck,
  • Henrik Vestergaard,
  • Sara Vieira-Silva,
  • Anita Yvonne Voigt,
  • Jian Wang,
  • Jun Wang,
  • Jean Weissenbach,
  • Yohanan Winogradski,
  • Takuji Yamada,
  • Huanming Yang,
  • Erwin G. Zoetendal,
  • Francisco Guarner,
  • S. Dusko Ehrlich

摘要

Inflammatory bowel diseases affect ever-increasing numbers of individuals worldwide. Alterations of the intestinal microbiome were reported for Crohn’s disease and at relapse in Ulcerative Colitis (UC); they were not clearly detected in UC at remission. Here we report the characterization of the microbiome by quantitative metagenomics in a cohort of 121 individuals, composed of 65 UC adult patients in remission and 56 healthy controls. A cross-sectional comparison revealed substantial microbiome differences, patients in remission having lower microbiome richness and paucity of the Ruminococcus species driven enterotype. The observed microbiome alterations allowed robust classification of patients by intestinal species abundance, yielding an area under the curve (AUC) of 0.87 in a Receiver-Operator Characteristic (ROC) analysis. Loss of richness was linked to an aggressive UC phenotype and to the importance of past relapses; it was associated with a worse IBD quality of life score (IBDQ-36). Unexpectedly, onset of inflammatory bouts, as assessed by white blood cell count and fecal calprotectin levels, was associated with higher richness; in a longitudinal study of patients at high risk of disease flare, we observed a link between increasing gut microbiome richness over time and calprotectin level, in turn related to clinical inflammatory response and relapse.