Lactoferrin: a review Original paper

What Was Reviewed?

The article offers a foundational synthesis of the biological properties, mechanisms, and therapeutic roles of lactoferrin (Lf), a multifunctional glycoprotein found in milk, secretions from exocrine glands, and neutrophil granules. As a member of the transferrin family, lactoferrin primarily binds iron but exerts a wide range of biological effects that extend beyond its iron-binding capabilities. This review discusses lactoferrin’s molecular structure, synthesis, metabolism, receptor interactions, and its influence on various physiological and pathological processes, including microbial infections, immune responses, inflammation, cancer progression, and bone metabolism.

Who Was Reviewed?

This review draws from in vitro experiments, animal studies, and human clinical and observational data, examining how lactoferrin behaves across various biological systems and species. Populations include neonates, pregnant women, and individuals exposed to pathogens or inflammatory conditions. Animal models such as rodents, cattle, rabbits, and horses also inform the physiological relevance of lactoferrin in veterinary and human health. The review compares lactoferrin concentrations and functions across species and contexts, emphasizing its potential in both human and veterinary medicine.

Most Important Findings?

Lactoferrin exerts potent antimicrobial effects by sequestering iron, thereby limiting bacterial growth, while simultaneously promoting beneficial microbiota such as Lactobacillus and Bifidobacterium. This dual action defines it as a major microbial association (MMA) molecule with both prebiotic and antimicrobial characteristics. It demonstrates direct bactericidal effects independent of iron binding, especially through its N-terminal domain and pepsin-derived fragments like lactoferricin. Lf also prevents biofilm formation (e.g., Pseudomonas aeruginosa) and blocks pathogen adhesion to host cells.

Beyond bacteria, lactoferrin inhibits viral entry by binding to glycosaminoglycans on host cells, disrupting infections from HSV, CMV, HIV, and others. It also demonstrates antiparasitic effects via iron competition and membrane disruption. Immunologically, Lf modulates inflammation by suppressing TNF-α, IL-1β, and IL-6 while upregulating IL-10, and interacts with immune cells such as neutrophils, macrophages, and NK cells. Its tumor-suppressive activity involves cell-cycle arrest, increased Fas-mediated apoptosis, and enhanced NK cell cytotoxicity.

The review reinforces lactoferrin’s microbial and immunomodulatory actions by highlighting its presence at mucosal sites, where it maintains barrier integrity and regulates microbial colonization. They have documented its effects across several species, particularly in humans and cattle, where lactoferrin concentrations correlate with stages of development, lactation, and immune status.

What Are the Implications of This Review?

This review highlights lactoferrin as a promising, naturally occurring therapeutic agent that interfaces meaningfully with the microbiome, immune system, and inflammatory processes. Its ability to regulate microbial populations while enhancing host defense mechanisms positions it as a vital molecule for managing infections, supporting mucosal immunity, and mitigating inflammatory diseases. Its broad spectrum of action, from antimicrobial and antiviral defense to cancer inhibition and bone support, makes lactoferrin highly relevant in both clinical and veterinary applications. For clinicians, lactoferrin represents an opportunity to integrate a microbiome-altering compound into therapeutic protocols for neonatal care, gastrointestinal disorders, chronic inflammation, and immune modulation.