Prader–Willi syndrome and the gut microbiota–endocrine–brain axis in hyperphagia and metabolic dysfunction
- 1Department of Pediatrics, The Second Hospital of Hebei Medical University
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.
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BibTeX
@article{wang2026praderwilli,
title = {{Prader–Willi syndrome and the gut microbiota–endocrine–brain axis in hyperphagia and metabolic dysfunction}},
author = {Kaixi Wang and Yutong Xing and Xinyu Ma and Yetong Jin and Huifeng Zhang and Xue Yan},
journal = {Frontiers in Endocrinology},
year = {2026},
month = nov,
doi = {10.3389/fendo.2026.2007004},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.2007004/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Prader–Willi syndrome and the gut microbiota–endocrine–brain axis in hyperphagia and metabolic dysfunction
AU - Kaixi Wang
AU - Yutong Xing
AU - Xinyu Ma
AU - Yetong Jin
AU - Huifeng Zhang
AU - Xue Yan
PY - 2026
DA - 2026/11/09
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.2007004
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.2007004/full
AB - 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.
SN - 1664-2392
ER -