Microscopic Colitis Patients Possess a Perturbed and Inflammatory Gut Microbiota

Sandra Hertz, Juliana Durack, Karina Frahm Kirk, Hans Linde Nielsen, Din L Lin, Douglas Fadrosh, Kole Lynch, Yvette Piceno, Ole Thorlacius-Ussing, Henrik Nielsen, Susan V Lynch

Research output: Contribution to journalJournal articleResearchpeer-review

12 Citations (Scopus)

Abstract

BACKGROUND: Microscopic colitis (MC), an inflammatory disease of the colon, is characterized by chronic non-bloody diarrhea with characteristic inflammation and for some, collagen deposits in mucosal biopsies. The etiology of MC is unclear, although previous findings implicate luminal factors and thus the gut microbiome. However, the relationships between fecal microbiota and MC are relatively unexplored.

METHODS: Stool microbiota of MC (n = 15) and healthy controls (HC; n = 21) were assessed by 16S rRNA V4 amplicon sequencing and analysis performed in QIIME. Gut microbiota functions were predicted using Piphillin and inflammatory potential assessed using an in vitro HT29 colonocyte cell assay.

RESULTS: MC patient fecal microbiota were less diverse (Faiths index; p < 0.01) and compositionally distinct (PERMANOVA, weighted UniFrac, R2 = 0.08, p = 0.02) compared with HC subjects. MC microbiota were significantly depleted of members of the Clostridiales, enriched for Prevotella and more likely to be dominated by this genus (Chi2 = 0.03). Predicted pathways enriched in MC microbiota included those related to biosynthesis of antimicrobials, and sphingolipids, to glycan degradation, host defense evasion, and Th17 cell differentiation and activation. In vitro, exposure of cultured colonocytes to cell-free products of MC patient feces indicates reduced gene expression of IL-1B and occludin and increased GPR119 and the lymphocyte chemoattractant CCL20.

CONCLUSION: MC gut microbiota are distinct from HC and characterized by lower bacterial diversity and Prevotella enrichment and distinct predicted functional pathways. Limited in vitro experiments indicate that compared with cell-free products from healthy fecal microbiota, MC microbiota induce distinct responses when co-cultured with epithelial cells, implicating microbiota perturbation in MC-associated mucosal dysfunction.

Original languageEnglish
JournalDigestive Diseases and Sciences
Volume67
Issue number6
Pages (from-to)2433–2443
Number of pages11
ISSN0163-2116
DOIs
Publication statusPublished - Jun 2022

Bibliographical note

© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Keywords

  • 16S rRNA sequencing
  • Dysbiosis
  • Gastrointestinal microbiota
  • Microscopic colitis
  • Prevotella

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