Background/Objectives:The combination of energy dense diets and reduced energy expenditure in modern society has escalated the prevalence of obesity and obesity-related comorbidities. Among these disease states, type-2 diabetics (T2D) are disproportionately associated with obesity, suggesting a shared etiology. In conjunction with defects in hormonal and inflammatory states, obesity and T2D are also characterized by dysbiosis.Methods:We have recently described the beneficial effects of duodenal nutrient exclusion, as induced by the duodenal endoluminal sleeve (DES); including body weight loss, prevented fat mass accumulation, and improved glucose tolerance in the ZDF rat, a rodent model of obesity and type-2 diabetes (T2D). To assess the relative role of DES on hindgut microbiota in the context of these metabolic changes, we analyzed cecal samples from rats implanted with a duodenal endoluminal sleeve (DES), or a sham control of this procedure. A group of pair-fed (pf) sham controls was also included to account for changes induced by reduced body weight and food intake.Results:Analysis of hindgut microbiota following DES in the ZDF rat elucidated discrete changes in several microbial populations including a reduction in Paraprevotella family members of the Clostridiales order along with an increase in Akkermansia muciniphila and species of the Allobaculum and Bifidobacterium genera.Conclusions:Altogether, these observations suggest that like Roux-en Y gastric bypass (RYGB) and Metformin, regulation of gut microbiota may be a contributing factor to the therapeutic effects of DES.