The human gut microbiota contributes to type-2 diabetes non-resolution 5-years after Roux-en-Y gastric bypass
Jean Debédat, Tiphaine Le Roy, Lise Voland, Eugeni Belda, Rohia Alili, Solia Adriouch, Pierre Bel Lassen, Kazuyuki Kasahara, Evan R. Hutchison, Laurent Genser, Lícia Torres, Camille Gamblin, Christine Rouault, Jean‐Daniel Zucker, Nathalie Kapel, Christine Poitou, Geneviève Marcelin, Federico E. Rey, Judith Aron‐Wisnewsky, Karine Clément
Abstract
. A key observation is that patients who underwent major metabolic improvements do not harbor this enrichment in Bacteroidia, as those who presented mild cases of T2D at all times. In a separate group of 36 patients with similar baseline clinical characteristics and preoperative GM sequencing, we showed that this increase in Bacteroidia was already present at baseline in the most severe cases of T2D. To explore the causal relationship linking this enrichment in Bacteroidia and metabolic alterations, we selected 13 patients across T2D severity clusters at 5-years and performed fecal matter transplants in mice. Our results show that 14 weeks after the transplantations, mice colonized with the GM of Severe donors have impaired glucose tolerance and insulin sensitivity as compared to Mild-recipients, all in the absence of any difference in body weight and composition. GM sequencing of the recipient animals revealed that the hallmark T2D-severity associated bacterial features were transferred and were associated with the animals' metabolic alterations. Therefore, our results further establish the GM as a key contributor to long-term glucose metabolism improvements (or lack thereof) after RYGB.