Immunomodulatory effects of lactoferrin 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 comprehensive review of the immunomodulatory effects of lactoferrin (Lf), a multifunctional iron-binding glycoprotein found abundantly in mammalian colostrum and other secretions. The review synthesizes evidence from in vitro and in vivo studies to explore Lf’s diverse roles in immune modulation, antimicrobial defense, and its therapeutic potential. It places special emphasis on Lf’s interactions with various immune cells and outlines how these interactions affect innate and adaptive immune responses. Additionally, the review discusses lactoferrin’s emerging applications in infant formulas, antimicrobial therapies, chronic inflammation, and potentially in oncology and metabolic disorders.
Who Was Reviewed?
The review aggregates findings across multiple model systems, including human and animal in vitro cell lines and in vivo studies conducted in mice, piglets, and preterm infants. It references clinical data involving human supplementation trials, particularly in neonates and immunocompromised individuals, along with recombinant and bovine lactoferrin applications across species.
What Were the Most Important Findings?
Lactoferrin modulates immunity by influencing both innate and adaptive arms. It suppresses pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), promotes anti-inflammatory mediators (IL-10), and interacts with key immune receptors like CD14 and TLR4 to temper inflammatory responses. Notably, Lf blocks LPS-CD14 interaction, preventing downstream NF-κB activation, and enhances antigen presentation by upregulating dendritic cell function and stimulating Th1 responses. It also boosts B-cell maturation and IgA/IgG secretion, acting as an immune bridge molecule. On a microbiome level, Lf inhibits pathogenic colonization and biofilm formation while supporting the proliferation of beneficial gut bacteria by promoting mucosal immunity and epithelial barrier integrity, especially crucial in neonates with immature guts. Lf’s impact on early microbial colonization and interaction with Lf receptors in intestinal brush border cells underscores its role in shaping the neonatal immune-microbiome axis.
What Are the Implications of This Review?
The review establishes lactoferrin as a potent immunomodulatory agent with both therapeutic and prophylactic relevance. Its ability to bridge innate and adaptive immunity, regulate cytokine networks, and reduce inflammation presents major opportunities in managing inflammatory diseases, sepsis, neonatal necrotizing enterocolitis, and microbial infections. From a microbiome perspective, Lf represents a natural intervention that supports epithelial integrity, regulates microbial-host interactions, and facilitates immune tolerance during early colonization. Clinically, this positions Lf as a valuable adjunct in infant formula, immunocompromised care, and potentially as an anti-inflammatory nutraceutical or therapeutic biologic in chronic disease.