162655 20251017144654.0 doi 10.1016/j.jnutbio.2025.110073 sideral 145120 ART-2025-145120 eng Buey, Berta (orcid)0000-0002-8467-0356 Protective role of bovine lactoferrin in modulating the intestinal serotonergic system: implications in intestinal inflammation 2025 Access copy available to the general public Unrestricted Bovine lactoferrin (bLf) is a multifunctional milk glycoprotein with diverse biological activities pivotal for gastrointestinal health. This study investigates the modulatory effects of bLf on the intestinal serotonergic system and its implications for intestinal inflammation and homeostasis. Intestinal serotonergic system plays a critical role in gut homeostasis, regulating various physiological processes via serotonin (5-HT) signaling. Dysregulation of this system contributes to inflammatory bowel diseases, characterized by chronic inflammation and disrupted intestinal function. We evaluated the impact of bLf on the intestinal serotonergic system in vitro and in vivo. In Caco-2/TC7 cells, bLf treatment enhanced serotonin transporter (SERT) activity and mRNA expression and modulated the mRNA levels of several serotonin receptors (5-HTRs). In mice, oral bLf administration upregulated SERT, tryptophan hydroxylase 2 (TPH2), and 5-HTRs mRNA expression in the ileum. Moreover, in a dextran sodium sulphate (DSS)-induced colitis model, bLf attenuated clinical signs of colonic inflammation, while normalizing the mRNA expression of SERT, TPH1, TPH2, and 5-HTRs in colon. These findings highlight the ability of bLf to modulate key components of the intestinal serotonergic system under both physiological and inflammatory conditions. Given the leading role of serotonin in gut-brain axis and immune regulation, bLf emerges as a promising functional food ingredient with potential for preventing or managing intestinal inflammation. Further exploration of its dietary applications may support the development of innovative nutritional strategies targeting gut-related disorders. info:eu-repo/grantAgreement/ES/DGA/A20-20R info:eu-repo/grantAgreement/ES/DGA/A20-23R info:eu-repo/grantAgreement/ES/MINECO/AGL2017-82987 info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Abad, Inés Bellés, Andrea (orcid)0000-0002-6546-6149 Castro, Marta Universidad de Zaragoza (orcid)0000-0001-8584-3979 Valero, Marta Sofía Universidad de Zaragoza (orcid)0000-0002-2231-7565 Arruebo, María Pilar Universidad de Zaragoza (orcid)0000-0002-2114-0577 Grasa, Laura Universidad de Zaragoza (orcid)0000-0002-5306-9365 Sánchez, Lourdes Universidad de Zaragoza (orcid)0000-0001-5964-823X Plaza, Miguel Ángel Universidad de Zaragoza (orcid)0000-0002-7412-2073 Mesonero, José Emilio Universidad de Zaragoza (orcid)0000-0003-4758-3998 Latorre, Eva Universidad de Zaragoza (orcid)0000-0002-5797-3909 1012 410 Universidad de Zaragoza Dpto. Farmac.Fisiol.y Med.L.F. Área Fisiología 1002 050 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Biología Celular 2008 780 Universidad de Zaragoza Dpto. Produc.Animal Cienc.Ali. Área Tecnología de Alimentos 146 (2025), 110073 [11 pp.] J. nutr. biochem. Journal of Nutritional Biochemistry 0955-2863 1656085 http://zaguan.unizar.es/record/162655/files/texto_completo.pdf Versión publicada 2880137 http://zaguan.unizar.es/record/162655/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:162655 articulos driver 2025-10-17-14:37:39 ARTICLE