Compositional and Temporal Changes in the Gut Microbiome of Pediatric Ulcerative Colitis Patients Are Linked to Disease Course

Melanie Schirmer, Lee Denson, Hera Vlamakis, Eric A. Franzosa, Sonia Thomas, Nathan M. Gotman, Paul Rufo, Susan S. Baker, Cary Sauer, James Markowitz, Marian Pfefferkorn, Maria Oliva-Hemker, Joel Rosh, Anthony Otley, Brendan Boyle, David Mack, Robert Baldassano, David Keljo, Neal LeLeiko, Melvin HeymanAnne Griffiths, Ashish S. Patel, Joshua Noe, Subra Kugathasan, Thomas Walters, Curtis Huttenhower, Jeffrey Hyams, Ramnik J. Xavier

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Evaluating progression risk and determining optimal therapy for ulcerative colitis (UC) is challenging as many patients exhibit incomplete responses to treatment. As part of the PROTECT (Predicting Response to Standardized Colitis Therapy) Study, we evaluated the role of the gut microbiome in disease course for 405 pediatric, new-onset, treatment-naive UC patients. Patients were monitored for 1 year upon treatment initiation, and microbial taxonomic composition was analyzed from fecal samples and rectal biopsies. Depletion of core gut microbes and expansion of bacteria typical of the oral cavity were associated with baseline disease severity. Remission and refractory disease were linked to species-specific temporal changes that may be implicative of therapy efficacy, and a pronounced increase in microbiome variability was observed prior to colectomy. Finally, microbial associations with disease-associated serological markers suggest host-microbial interactions in UC. These insights will help improve existing treatments and develop therapeutic approaches guiding optimal medical care. Many patients exhibit incomplete responses to ulcerative colitis (UC) therapy. Schirmer et al. investigate the gut microbiome's role in pediatric UC treated with two conventional therapies. Baseline and longitudinal microbial trends are implicated in disease severity and progression, including remission and colectomy requirement. These insights may motivate new therapeutic approaches.

Original languageEnglish (US)
Pages (from-to)600-610.e4
JournalCell Host and Microbe
Volume24
Issue number4
DOIs
StatePublished - Oct 10 2018

Keywords

  • 5ASA
  • colectomy
  • corticosteroids
  • disease course
  • gut microbiome
  • host-microbial interactions
  • pediatric ulcerative colitis
  • response to therapy
  • serological markers
  • treatment-naive

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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    Schirmer, M., Denson, L., Vlamakis, H., Franzosa, E. A., Thomas, S., Gotman, N. M., Rufo, P., Baker, S. S., Sauer, C., Markowitz, J., Pfefferkorn, M., Oliva-Hemker, M., Rosh, J., Otley, A., Boyle, B., Mack, D., Baldassano, R., Keljo, D., LeLeiko, N., ... Xavier, R. J. (2018). Compositional and Temporal Changes in the Gut Microbiome of Pediatric Ulcerative Colitis Patients Are Linked to Disease Course. Cell Host and Microbe, 24(4), 600-610.e4. https://doi.org/10.1016/j.chom.2018.09.009