Plant‐Derived Bioactives and PPAR Signaling in Functional Dyspepsia: Mechanistic Insights and Therapeutic Perspectives

Functional dyspepsia (FD) is a common disorder of gut-brain interaction in which gastric sensorimotor abnormalities may coexist with impaired duodenal barrier function, low-grade immune activation, and altered neuroimmune signaling. Peroxisome proliferator-activated receptors (PPARs) are relevant to this emerging model because they regulate epithelial differentiation, inflammatory responses, mitochondrial metabolism, redox balance, and lipid-mediator signaling. Impaired duodenal release of palmitoylethanolamide (PEA) provides direct translational evidence that defective PPARα-dependent lipid signaling may contribute to FD. Experimental studies further suggest that several plant-derived bioactives modulate PPAR-related pathways and other mechanisms involved in mucosal adaptation. Whether these effects restore duodenal function or improve clinically meaningful outcomes in humans remains uncertain. This review examines PPAR signaling as a mechanistic link between duodenal dysfunction and the actions of plant-derived bioactives. Therefore, we distinguish disease-specific evidence from findings obtained in other experimental settings and identify priorities for the development of mechanism-based phytotherapy in FD.