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Original article
Major microbiota dysbiosis in severe obesity: fate after bariatric surgery
  1. Judith Aron-Wisnewsky1,2,
  2. Edi Prifti3,4,
  3. Eugeni Belda3,4,
  4. Farid Ichou5,
  5. Brandon D Kayser1,
  6. Maria Carlota Dao1,
  7. Eric O Verger1,
  8. Lyamine Hedjazi5,
  9. Jean-Luc Bouillot6,
  10. Jean-Marc Chevallier7,
  11. Nicolas Pons8,
  12. Emmanuelle Le Chatelier8,
  13. Florence Levenez8,
  14. Stanislav Dusko Ehrlich8,
  15. Joel Dore8,
  16. Jean-Daniel Zucker3,4,
  17. Karine Clément1,2
  1. 1Sorbonne Université, INSERM, NutriOmics Team, ICAN, Paris, France
  2. 2Assistance Publique Hôpitaux de Paris, Nutrition Department, CRNH Ile de France, Pitié-Salpêtrière Hospital, Paris, France
  3. 3Unité de Modélisation Mathématique et Informatique des Systèmes Complexes, IRD, Sorbonne Université, UMMISCO
  4. 4Integromics, Institute of Cardiometabolism and Nutrition, ICAN, Paris, France
  5. 5Metabolomics Platforms, Institute of Cardiometabolism and Nutrition ICAN, Paris, France
  6. 6Visceral surgery department of Ambroise Paré, Assistance Publique Hôpitaux de Paris, APHP, Paris, France
  7. 7Visceral Surgery Department of HEGP, Assistance Publique Hôpitaux de Paris, APHP, Paris, France
  8. 8MGP MetaGénoPolis, INRA, Université Paris-Saclay, Jouy-en-Josas, France
  1. Correspondence to Dr Karine Clément, Nutrition department, Faculty of medicine INSERM, ICAN, Pitié-Salpêtrière Hospital, Sorbonne University, Paris 75013, France; Karine.Clement{at}psl.aphp.fr

Abstract

Objectives Decreased gut microbial gene richness (MGR) and compositional changes are associated with adverse metabolism in overweight or moderate obesity, but lack characterisation in severe obesity. Bariatric surgery (BS) improves metabolism and inflammation in severe obesity and is associated with gut microbiota modifications. Here, we characterised severe obesity-associated dysbiosis (ie, MGR, microbiota composition and functional characteristics) and assessed whether BS would rescue these changes.

Design Sixty-one severely obese subjects, candidates for adjustable gastric banding (AGB, n=20) or Roux-en-Y-gastric bypass (RYGB, n=41), were enrolled. Twenty-four subjects were followed at 1, 3 and 12 months post-BS. Gut microbiota and serum metabolome were analysed using shotgun metagenomics and liquid chromatography mass spectrometry (LC-MS). Confirmation groups were included.

Results Low gene richness (LGC) was present in 75% of patients and correlated with increased trunk-fat mass and comorbidities (type 2 diabetes, hypertension and severity). Seventy-eight metagenomic species were altered with LGC, among which 50% were associated with adverse body composition and metabolic phenotypes. Nine serum metabolites (including glutarate, 3-methoxyphenylacetic acid and L-histidine) and functional modules containing protein families involved in their metabolism were strongly associated with low MGR. BS increased MGR 1 year postsurgery, but most RYGB patients remained with low MGR 1 year post-BS, despite greater metabolic improvement than AGB patients.

Conclusions We identified major gut microbiota alterations in severe obesity, which include decreased MGR and related functional pathways linked with metabolic deteriorations. The lack of full rescue post-BS calls for additional strategies to improve the gut microbiota ecosystem and microbiome–host interactions in severe obesity.

Trial registration number NCT01454232.

  • intestinal tract
  • intestinal bacteria
  • gastric surgery
  • obesity
  • obesity surgery

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Footnotes

  • JA-W, EP and EB contributed equally.

  • Contributors JA-W and KC conceptualised the study. JA-W, EP and KC drafted the manuscript and have primary responsibility for the final content of the manuscript. EP, EB, JA-W, EOV, J-DZ, MCD and BDK analysed the data, conducted the statistical tests, and drafted the tables and figures. JLB and J-MC performed the bariatric surgeries. NP, ELC, FL, SDE and JD produced metagenomics data and determined the microbiome composition. FI and LH produced the metabolomics data. All authors read and approved the final manuscript.

  • Funding This project is supported by the ’Programme Hospitalier de Recherche Clinique' (PHRC Microbaria AOM10285/P100111 to KC). JA-W received a grant from Institut Appert, from Nestlé research and from Aviesan alliance nationale pour les sciences de la vie et de la santé ITMO santé publique. Partners have received funding from the European Union’s Seventh Framework Programme (FP7) for research, technological development and demonstration under grant agreement HEALTH-F4-2012-305312 (MetaCardis) and from the French ’Investissement d’Avenir' FORCE and the MetaGenoPolis grant ANR-11-DPBS-0001. Clinical investigation is performed at the Human Nutrition Research Center (CRNH Ile de France), Pitié-Salpêtrière Hospital.

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval Ethical approval was obtained from the Pitié-Salpêtrière Hospital Research Ethics Committee (CPP Ile-de-France).

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

  • Correction notice This article has been corrected since it published Online First. Lyamine Hedjazi’s name has been corrected.

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