Mucosal microbial load in Crohn's disease: A potential predictor of response to faecal microbiota transplantation

Guillaume Sarrabayrouse, Stefania Landolfi, Marta Pozuelo, Joseane Willamil, Encarna Varela, Allison Clark, David Campos, Claudia Herrera, Alba Santiago, Kathleen Machiels, Severine Vermeire, Marc Martí, Eloy Espin, Chaysavanh Manichanh*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

21 Citations (Scopus)

Abstract

Background: The remission of Crohn's disease (CD) can be accomplished by faecal microbiota transplantation (FMT). However, this procedure has a low success rate, which could be attributed to mis-communication between recipient intestinal mucosa and donor microbiota. Methods: Here we used a human explant tissue model and an in vivo mouse model to examine changes in recipient intestinal mucosa upon contact with a faecal suspension (FS) obtained from a healthy donor. CD patients provided resected inflamed and non-inflamed mucosal tissues, whereas control colonic mucosa samples were collected from colorectal cancer patients. For the models, mucosal microbiome composition and tissue response were evaluated. Findings: We show that cytokine release and tissue damage were significantly greater in inflamed compared to non-inflamed CD tissues. Moreover, mucosal samples harbouring an initial low microbial load presented a shift in composition towards that of the FS, an increase in the relative count of Faecalibacterium prausnitzii, and a higher secretion of anti-inflammatory cytokine IL-10 compared to those with a high microbial load. Interpretation: Our results indicate that FMT during active inflammatory disease can compromise treatment outcome. We recommend the stratification of FMT recipients on the basis of tissue microbial load as a strategy to ensure successful colonization. Funding: This study was supported by grants from the Instituto de Salud Carlos III/FEDER (PI17/00614), the European Commission: (INCOMED-267128) and PERIS (SLT002/16). K.M. is a postdoctoral fellow and S.V. a senior clinical investigator of the Fund for Scientific Research Flanders, Belgium (FWO-Vlaanderen).

Original languageEnglish
Article number102611
JournalEBioMedicine
Volume51
DOIs
Publication statusPublished - Jan 2020

Keywords

  • Anti-inflammatory cytokines
  • Crohn's disease
  • FMT
  • Intestinal microbiome
  • Microbial load
  • Recipient stratification

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