Author:
Aron-Wisnewsky Judith,Prifti Edi,Belda Eugeni,Ichou Farid,Kayser Brandon D,Dao Maria Carlota,Verger Eric O,Hedjazi Lyamine,Bouillot Jean-Luc,Chevallier Jean-Marc,Pons Nicolas,Le Chatelier Emmanuelle,Levenez Florence,Ehrlich Stanislav Dusko,Dore Joel,Zucker Jean-Daniel,Clément Karine
Abstract
ObjectivesDecreased 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.DesignSixty-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.ResultsLow 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.ConclusionsWe 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 numberNCT01454232.
Funder
Fondation Nestlé
Institut Appert
Programme Hospitalier de Recherche Clinique
Fondation de l’Avenir pour la Recherche Médicale Appliquée
FP7 Health
Aviesan alliance nationale pour les sciences de la vie et de la santé ITMO santé publique
Human Nutrition Research Center (CRNH Ile de France), Pitié-Salpêtrière Hospital
Cited by
297 articles.
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