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Original article
Fungi participate in the dysbiosis of gut microbiota in patients with primary sclerosing cholangitis
  1. Sara Lemoinne1,2,3,
  2. Astrid Kemgang1,2,3,
  3. Karima Ben Belkacem1,2,3,
  4. Marjolène Straube1,4,
  5. Sarah Jegou1,4,
  6. Christophe Corpechot1,2,3,
  7. Saint-Antoine IBD Network,
  8. Olivier Chazouillères1,2,3,
  9. Chantal Housset1,2,3,
  10. Harry Sokol1,4,5
  1. 1 Centre de Recherche Saint-Antoine (CRSA), Sorbonne Université, INSERM, Paris, France
  2. 2 Institute of Cardiometabolism and Nutrition (ICAN), Sorbonne Université, INSERM, Paris, France
  3. 3 Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis (MIVB-H), Department of Hepatology, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
  4. 4 Department of Gastroenterology, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
  5. 5 UMR1319 Micalis, AgroParisTech, INRA, Jouy-en-Josas, France
  1. Correspondence to Prof Harry Sokol, Department of Gastroenterology, AP-HP, Hôpital Saint-Antoine, Paris 75012, France; harry.sokol{at}aphp.fr

Abstract

Objective Patients with primary sclerosing cholangitis (PSC) were previously shown to display a bacterial gut dysbiosis but fungal microbiota has never been examined in these patients. The aim of this study was to assess the fungal gut microbiota in patients with PSC.

Design We analysed the faecal microbiota of patients with PSC and concomitant IBD (n=27), patients with PSC and no IBD (n=22), patients with IBD and no PSC (n=33) and healthy subjects (n=30). Bacterial and fungal composition of the faecal microbiota was determined using 16S and ITS2 sequencing, respectively.

Results We found that patients with PSC harboured bacterial dysbiosis characterised by a decreased biodiversity, an altered composition and a decreased correlation network density. These alterations of the microbiota were associated with PSC, independently of IBD status. For the first time, we showed that patients with PSC displayed a fungal gut dysbiosis, characterised by a relative increase in biodiversity and an altered composition. Notably, we observed an increased proportion of Exophiala and a decreased proportion of Saccharomyces cerevisiae. Compared with patients with IBD and healthy subjects, the gut microbiota of patients with PSC exhibited a strong disruption in bacteria-fungi correlation network, suggesting an alteration in the interkingdom crosstalk.

Conclusion This study demonstrates that bacteria and fungi contribute to gut dysbiosis in PSC.

  • gut microbiota
  • fungi
  • inflammatory bowel disease
  • primary sclerosing cholangitis

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Footnotes

  • 36 CH and HS share senior authorship

  • SL and AK authors share first authorship

  • 36 ‡The list of members of the Saint-Antoine Inflammatory Bowel Disease (IBD)Network is provided as Supplementary Material.

  • Contributors SL, AK: study execution, collection and analysis of data, drafting of the manuscript. KBB, MS, SJ: acquisition of data. HS: statistical analyses, interpretation of data, design of the figures. HS, CH: study concept, design and supervision. OC, CH: fund raising for the study. CC, OC, HS, CH: critical revision of the manuscript. All authors approved the final version. Saint-Antoine IBD Network provided the patients.

  • Funding This study was supported by the Microbiome Foundation.

  • Competing interests None declared.

  • Ethics approval The study was approved by the regional ethics committee for human studies (Comité de Protection des Personnes Ile-de-France IV, IRB 00003835 Suivitheque study; registration number 2012/05NICB).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Collaborators Members of the Saint-Antoine IBD Network: Arrivé Lionel, Beaugerie Laurent, Bourrier Anne, Camus Marine, ChafaiNajim, Chambenois Édouard, ChaputUlriikka, Delattre Charlotte, Martineau Chloé, Cholley Monnier Laurence, DeboveClotilde, Dray Xavier, Fléjou Jean-François, Le Gall Guillaume, Hoyeau Nadia, Kirchgesner Julien, Landman Cecilia, LevèvreJérémie, Marteau Philippe, Nion-Larmurier Isabelle, Ozenne Violaine, Parc Yann,Seksik Philippe, Sokol Harry, Svrcek Magali.

  • Correction notice This article has been corrected since it published Online First. The collaborator statement has been added.

  • Patient consent for publication Obtained.

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