THE ROLE OF PEPTIDE YY IN COLITIS AND GUT-BRAIN SIGNALING

Inflammatory bowel disease (IBD) is not only a gastrointestinal disorder but is also closely linked to brain function, with many patients experiencing anxiety and depression; however, the underlying gut–brain mechanisms remain unclear. Peptide YY (PYY) is a gut hormone secreted by the enteroendocrine cells, classically known to regulate gut motility, secretion, and satiety. In this study, we investigated the role of PYY in colitis and colitis-induced behavioral disturbances. Using wild-type and Pyy deficient (Pyy-KO) mice, we established a dextran sulfate sodium (DSS)-induced colitis model. Oral PYY administration was applied to assess potential therapeutic effects. Disease activity was evaluated by body weight loss and disease activity index (DAI) scores, while behavioral changes were assessed using the elevated plus maze, open field test, and splash test. Fecal microbiota composition was analysed by 16S rRNA gene sequencing. In vitro, an Electric Cell-substrate Impedance Sensing (ECIS) system was used to measure barrier integrity in primary human colonic epithelial cells. Pyy-KO mice exhibited higher DAI scores and greater weight loss following DSS treatment, along with altered behavioral responses. Both Pyy deficiency and DSS treatment significantly changed gut microbial composition. Oral PYY administration modulated behaviour but did not alter colitis severity. In vitro, DSS increased epithelial permeability, providing a suitable model to assess direct effects of PYY on barrier function. These findings suggest that PYY influences gut–brain communication and behaviour during intestinal inflammation, while epithelial barrier dysfunction may contribute to these interactions.