ESPE Abstracts

Background: Prader–Willi syndrome (PWS) is a rare genetic disorder associated with hyperphagia, and excessive weight gain. Patients with PWS are at elevated risk of developing morbid obesity and associated life-threatening complications. Although gut microbiota has been suggested to play a role in disease phenotypes, little is known about its composition and how it relates to hyperphagia.

Objective: The aim of this study was to characterize the gut bacterial and fungal communities of children with PWS, and to understand the role of the microbiome in the course and outcome of hyperphagia, obesity, and metabolic deterioration in PWS.

Methods: We conducted a case-control study with 29 children with genetic diagnosis of Prader–Willi syndrome and 28 age-, sex-, and body mass index-matched controls. The subjects were metabolically characterized and we obtained fecal samples to assess microbiota composition by 16S rRNA sequencing.

Results: The composition of the fecal microbiota in children with PWS differed from controls. Principal coordinate analysis (PCoA) showed a significant difference in the microbial community structure between the two groups. At the phylum level, the PWS group was characterized by a significantly lower abundance of Firmicutes and higher abundance of Actinobacteriota and Proteobacteria than in the control group. At the genus level, dysbiosis in PWS was characterized by a decrease in many butyrate-producing genera within Firmicutes, including Faecalibacterium, Blautia, Agathobacter, Lachnospira, and Prevotella, and an expansion of genera such as Streptococcus, Escherichia-Shigella, Klebsiella. Random forest analysis showed PWS-related specific gut microbiota profile has high predictive accuracy for this disorder with area under the curve (AUC) values of 0.9. The PICRUST functional prediction results revealed overall down-regulation of metabolic pathways and reduced capacity for complex carbohydrate metabolism in PWS group of gut microbiota.

Conclusions: The gut microbiota of children with PWS differs from matched controls. Microbial taxa linked to butyrate production and intestinal mucus metabolism are identified as putative mediators of metabolic regulation. Future studies should explore the effect of metabolic regulation with probiotics intervention on the degree of hyperphagia, obesity, insulin sensitivity and lipid metabolism.