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Microscopic Colitis Patients Possess a Perturbed and Inflammatory Gut Microbiota

Digestive Diseases and Sciences volume 67, pages 2433–2443 (2022)Cite this article

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.

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Acknowledgments

This study was supported in part by grants from the Lundbeck Foundation to the Innovation Centre, Denmark, and UCSF to fund the Danish American Research Exchange (DARE) fellowship program for Sandra Hertz

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Authors and Affiliations

  1. Department of Medicine, University of California San Francisco, 513 Parnassus Ave, S357D, Box 0538, San Francisco, CA, 94143, USA

    Sandra Hertz, Juliana Durack, Din L. Lin, Douglas Fadrosh, Kole Lynch, Yvette Piceno & Susan V. Lynch

  2. Department of Infectious Diseases, Aalborg University Hospital, Mølleparkvej 4, 7th floor, east wing, 9000, Aalborg, Denmark

    Sandra Hertz, Karina Frahm Kirk & Henrik Nielsen

  3. Department of Clinical Microbiology, Aalborg University Hospital, Mølleparkvej 10, 6th floor, 9000, Aalborg, Denmark

    Hans Linde Nielsen

  4. Department of Gastrointestinal Surgery, Aalborg University Hospital, Hobrovej 18-22, 9000, Aalborg, Denmark

    Ole Thorlacius-Ussing

  5. Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

    Hans Linde Nielsen, Ole Thorlacius-Ussing & Henrik Nielsen

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  1. Sandra Hertz
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Correspondence to Sandra Hertz.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Stool samples used in this study were collected in clinical studies approved by the Regional Ethics Committee of Northern Jutland, Denmark (N-20130070).

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Hertz, S., Durack, J., Kirk, K.F. et al. Microscopic Colitis Patients Possess a Perturbed and Inflammatory Gut Microbiota. Dig Dis Sci 67, 2433–2443 (2022). https://doi.org/10.1007/s10620-021-07045-8

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  • DOI: https://doi.org/10.1007/s10620-021-07045-8

Keywords

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