Abstract The gut microbiota has emerged as a key endocrine modulator that shapes host appetite regulation through its metabolites and their interactions with enteroendocrine and central neuroendocrine pathways. Microbial metabolites—including short-chain fatty acids, bile acid derivatives, indole compounds, and tryptophan-derived serotonin—activate receptors such as G-protein-coupled receptor 41/43, Takeda G protein-coupled receptor 5, and Toll-like receptor 4 on enteroendocrine cells, influence the secretion of appetite-related hormones including ghrelin, leptin, glucagon-like peptide-1, peptide YY, nesfatin-1, and cholecystokinin. These hormones subsequently modulate hypothalamic circuits, particularly the NPY/AgRP and POMC/CART pathways, establishing a mechanistic link between microbial signaling and central appetite control. Ghrelin serves as the primary orexigenic hormone, whereas leptin, glucagon-like peptide-1, peptide YY, nesfatin-1, and cholecystokinin collectively exert anorexigenic effects that promote satiety and energy homeostasis. Dysbiosis disrupts receptor-mediated endocrine signaling, alters hormonal secretion, and contributes to leptin resistance, impaired glucagon-like peptide-1 responsiveness, and dysregulated appetite—key features in obesity, insulin resistance, and metabolic syndrome. This review synthesizes current mechanistic insights into the microbiota–hormone axis and highlights how microbial modulation influences endocrine appetite regulation. Understanding these interactions provides a translational framework for developing microbiota-targeted endocrine therapies aimed at restoring metabolic balance and preventing obesity and related metabolic disorders.
Arvas et al. (Tue,) studied this question.