Lactoferrin (Lf) is an iron-binding milk glycoprotein that promotes the growth of selected probiotic strains. The effect of Lf on the growth and diversification of intestinal microbiota may have an impact on several issues, including (i) strengthening the permeability of the epithelial cell monolayer, (ii) favoring the microbial antagonism that discourages the colonization and proliferation of enteric pathogens, (iii) enhancing the growth and maturation of cell-monolayer components and gut nerve fibers, and (iv) providing signals to balance the anti- and pro-inflammatory responses resulting in gut homeostasis. Given the beneficial role of probiotics, this contribution aims to review the current properties of bovine and human Lf and their derivatives in in vitro probiotic growth and Lf interplay with microbiota described in the piglet model. By using Lf as a component in pharmacological products, we may enable novel strategies that promote probiotic growth while conferring antimicrobial activity against multidrug-resistant microorganisms that cause life-threatening diseases, especially in neonates.

Intestinal homeostasis encompasses a complex and balanced interplay among a wide array of components that collaborate to maintain gut barrier integrity. The appropriate function of the gut barrier requires the mucus layer, a sticky cushion of mucopolysaccharides that overlays the epithelial cell surface. Mucus plays a critical anti-inflammatory role by preventing direct contact between luminal microbiota and the surface of the epithelial cell monolayer. Moreover, mucus is enriched with pivotal effectors of intestinal immunity, such as immunoglobulin A (IgA). A fragile and delicate equilibrium that supports proper barrier function can be disturbed by stress. The impact of stress upon intestinal homeostasis results from neuroendocrine mediators of the brain-gut axis (BGA), which comprises a nervous branch that includes the enteric nervous system (ENS) and the sympathetic and parasympathetic nervous systems, as well as an endocrine branch of the hypothalamic-pituitary-adrenal axis. This review is the first to discuss the experimental animal models that address the impact of stress on components of intestinal homeostasis, with special emphasis on intestinal mucus and IgA. Basic knowledge from animal models provides the foundations of pharmacologic and immunological interventions to control disturbances associated with conditions that are exacerbated by emotional stress, such as irritable bowel syndrome.

Stress is a condition that maintains the homeostasis of the organism through the activation of different neuroendocrine pathways and secretion of wide array of chemical mediators including, corticotropin-releasing hormone (CRH), neurotransmitters and glucocorticoids hormones. These molecules fulfill important physiological functions but under stressful conditions, they can induce or aggravate a pathological state depending on type, severity and duration of stress. For this reason, the search of compounds that modulate the activity of the neuroendocrine pathways is crucial for the control of diseases associated with stressful situations. Bovine lactoferrin (bLf) is an iron-binding multifunctional glycoprotein that exhibits modulatory properties on neuroendocrine system. Bovine lactoferrin affects the production and secretion of neuroendocrine components of the hypothalamus-pituitary-adrenal (HPA) axis. Neuroendocrine mechanisms of bLf entails either the down- or up-modulation of adrenal corticosteroids via HPA pathway activation, nitric oxide (NO) generation and opioid nervous system pathway activation. This manuscript is focused to review the current contributions about of bLf modulatory actions on the response of hormones, neurotransmitters, involved in the stress and behavior. Sustained use of drugs for stress-associated dysfunctions lost efficacy and requires the dose increase by tolerance and drug dependence. Therefore, bLf may be included as therapeutic and/or adjunctive agent of drug-based therapies for the treatment with stress-associated emotional-disturbances.