Prader–Willi syndrome and the gut microbiota–endocrine–brain axis in hyperphagia and metabolic dysfunction
Year: 2026
Type: article
Abstract: Introduction Prader–Willi syndrome (PWS) is a genetic neuroendocrine disorder with developmental transitions from infant feeding difficulty to hyperphagia, altered body composition, and heterogeneous metabolic risk. The contribution of intestinal microbial activity to these features remains uncertain. Aim of the study To critically appraise evidence for microbiota–endocrine–brain interactions in PWS and identify testable mechanisms that may distinguish PWS from common obesity. Methods This mechanism-oriented narrative review integrates human PWS observational and intervention studies identified through a documented PubMed search to 16 September 2026, supplemented by targeted mechanistic literature. Evidence is distinguished by study population, experimental design, and causal directness. Results PWS cohorts show context-dependent microbiota differences without a reproducible disease-specific taxonomic signature. Donor-to-mouse transfers support transmissibility of selected metabolic traits, whereas dietary and strain-specific probiotic trials show heterogeneous endocrine and clinical findings. A randomized fiber intervention modified microbial and metabolite measures without significant improvement in hyperphagia. Microbial metabolites may influence insulin physiology and enteroendocrine GLP-1/PYY signaling; links to ghrelin dynamics, oxytocin, and POMC–α-MSH–MC4R circuitry remain incompletely demonstrated in PWS. Conclusion The gut microbiota is best regarded as a potential context-dependent modifier of genetically driven PWS rather than a proven cause of hyperphagia. Research should prioritize reproducible microbial functions, temporally matched metabolite–hormone measurements, and PWS-specific clinical endpoints.
Source: Frontiers in Endocrinology
Institution: Second Hospital of Hebei Medical University
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7225613335