A divergent gut bacterial composition associates with diabetes and obesity remission in Roux en Y gastric bypass surgery

Background and aims. Roux en Y gastric bypass (RYGB) surgery induces weight loss and recovers glucose homeostasis in patients with obesity and type 2 diabetes (T2D). Systemic improvement is accompanied by metabonome and gut microbial changes. However, it is unclear whether the microbiome actively participates in T2D remission and what role the change in intestinal macroanatomy plays. We assessed early post-surgery longitudinal changes in metabolism and gut bacterial composition on two variants of RYGB with differing lengths of biliopancreatic limb. Methods. Fifty patients were randomly assigned to a standard (50 cm) or long (150 cm) biliopancreatic limb length RYGB. Faecal samples were collected, and clinical markers measured prior to surgery, 1-3 weeks and 2-8 months after surgery. Bacterial composition was assessed by 16S rRNA gene sequencing. Clinical markers and gut bacteria were compared across time and limb length, and a dissimilarity measure was used to identify patients with a bacterial composition highly divergent to that from pre-surgery. Results. RYGB surgery improved clinical markers of T2D and obesity, but biliopancreatic limb length had little impact on this improvement. Alpha-diversity was similar among both surgeries, and an increase in Megamonas, Megasphaera and Negativicutes was observed in long limb patients. Patients with a markedly different bacterial composition to that of pre-surgery had higher alpha-diversity, lower Lactococcus and Mitsuokella genera abundance, and a higher T2D and obesity remission than non-divergent patients, who retained a more similar pre-surgery composition. Conclusion. Patients who achieve a higher gut bacterial community divergence post-surgery showed the greatest benefit from RYGB. Divergence associated taxa could be important players in T2D and obesity remission.