Gut microbiota in patients with Prader-Willi syndrome is linked to metabolic health despite severe obesity

ObjectiveThe gut microbiota has been implicated in the etiology of obesity and associated comorbidities such as diabetes. Patients with Prader-Willi syndrome (PWS) are severely obese but partly protected against insulin resistance. We hypothesized that the gut microbiota of PWS patients would confer improved metabolic health compared to obese controls and use PWS as a model to study the role of gut microbiota in the prevention of metabolic complications linked to obesity. DesignA case-control study where 17 adult PWS patients and 17 obese subjects matched for percentage fat mass, body fat mass index, gender and age were metabolically characterized by biochemical and anthropometric measurements was conducted. The fecal microbiota of patients and controls was profiled by 16S rRNA gene sequencing. The patients' parents were used as a non-obese control group. Stool samples from two PWS patients and two obese controls were used for fecal microbiota transplantations in germ-free mice to examine the impact of the microbiota on glucose metabolism.Results The composition of the fecal microbiota in patients with PWS differed from that of obese controls, and was characterized by higher phylogenetic diversity and increased abundance of several taxa such as Akkermansia, Desulfovibrio and Archaea, as well as decreased abundance of Dorea. Microbial taxa that were prevalent in the PWS microbiota were associated with markers of insulin sensitivity. The improved insulin resistance of PWS could be partly transmitted by fecal microbiota transplantations into germ-free mice.ConclusionThe gut microbiota of PWS patients is similar to that of their non-obese parents and might play a role for the protection of PWS patients from obesity-related metabolic complications.