Overview of Lactoferrin as a Natural Immune Modulator Original paper
Researched by:
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Divine Aleru
ID
Divine Aleru
I am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.
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Divine Aleru
Researched by:
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Divine Aleru
ID
Divine Aleru
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Divine Aleru
What Was Reviewed?
This paper is a detailed review of lactoferrin’s multifaceted role as a natural immune modulator, highlighting both its innate and adaptive immunological functions. It synthesizes findings from molecular, cellular, and systemic levels, addressing lactoferrin’s antimicrobial properties, cytokine modulation capabilities, and receptor interactions that drive immune balance. The review emphasizes lactoferrin’s structural features that allow it to bind to microbial components (like LPS), host receptors, and immune signaling molecules, thereby influencing immune responses at mucosal surfaces and beyond.
Who Was Reviewed?
The review draws from a broad body of in vivo and in vitro studies, including data from human and animal models. It reviews evidence involving polymorphonuclear neutrophils (PMNs), antigen-presenting cells (APCs), lymphocytes, and epithelial/endothelial cells. This paper also evaluates lactoferrin’s impact in both physiological and inflammatory contexts, including infection, allergy, and neurodegenerative conditions, with particular emphasis on its oral supplementation as a dietary immune intervention.
What Were the Most Important Findings?
Lactoferrin serves as a potent immune modulator by interacting with both pathogen-associated molecular patterns (PAMPs) and host receptors. It regulates cytokine balance—reducing pro-inflammatory mediators like TNF-α, IL-1, and IL-6, while enhancing IL-4 and IL-10. Lactoferrin binds and neutralizes LPS and unmethylated CpG DNA, thereby dampening toll-like receptor (TLR)-mediated inflammation. Notably, its N-terminal domain (especially lactoferricin and lactoferrampin peptides) mediates many of these effects through high-affinity interactions with cellular and microbial targets.
Lactoferrin also modulates immune cell activity by engaging various surface receptors, such as intelectin-1 and surface nucleolin. These interactions influence immune cell migration, cytokine release, and antigen presentation. Furthermore, lactoferrin’s ability to form complexes with immunoregulatory proteins like osteopontin and ceruloplasmin expands its functional repertoire. It acts as an alarmin, recruiting dendritic cells and monocytes and linking innate to adaptive immunity, while shaping the Th1/Th2 balance—a critical aspect for microbiome-host equilibrium.
What Are the Implications of This Review?
This review affirms lactoferrin as a versatile regulator of immune responses, positioning it as a central molecule for both microbial control and immune tolerance. Its capacity to simultaneously suppress excessive inflammation and support immune activation makes it a highly valuable agent for microbiome-integrated therapies. From a clinical standpoint, lactoferrin holds therapeutic potential for managing conditions involving chronic inflammation, infection, and immune dysregulation, including IBD, neonatal sepsis, and neuroinflammation. Its oral bioactivity also supports its application in functional foods and infant formulas designed to fortify immune resilience via gut-immune interactions.