A Randomized Crossover Fiber Intervention Study in Prader–Willi Syndrome: Insights into Metabolic and Microbiota Shifts

While increased fiber intake may benefit appetite and metabolism in the general population, its effects in individuals with Prader-Willi Syndrome (PWS), a condition characterized by hyperphagia, obesity and metabolic dysregulation, remain to be explored. This study assessed the effects of a fiber intervention on hyperphagia, metabolic health, and gut microbiota in individuals with PWS, and explored associations between changes in health markers and shifts in microbiota. Participants received either a high-dose fiber intervention (35g/day) or a control for 3 weeks. Following a washout period of 4 to 8 weeks, participants switched treatments for another 3 weeks. Fecal (bacterial 16S ribosomal RNA) and blood (immunometabolic markers, targeted metabolomics) samples were collected before and after each treatment. Fourteen participants (with a median age of 13.6 years, 8 [57.1%] were female) reported high tolerance to the fiber intervention. While it did not significantly alter hyperphagia or key metabolic markers, the fiber intervention led to shifts in gut microbiota diversity and increased the abundance of beneficial bacteria, such as Bifidobacterium longum and Faecalibacterium prausnitzii. Additionally, it altered fecal and serum metabolites, including a decrease in branched-chain fatty acids and an increase in serum C4-OH acylcarnitine. While this study did not observe significant changes in primary or secondary endpoints, it suggests that a short-term high-fiber intervention may induce beneficial shifts in gut microbiota and microbial metabolites in individuals with PWS. Further research is warranted to investigate the long-term effects and potential therapeutic applications of fiber interventions in PWS.