Protective role of bovine lactoferrin in modulating the intestinal serotonergic system: Implications in intestinal inflammation

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.