The Roles and Mechanisms of Direct and Indirect Prebiotic Activities of Lactoferrin and Its Application in Disease Control Original paper

What Was Reviewed?

This paper is a comprehensive review that synthesizes both in vitro and in vivo research on lactoferrin’s (LF) prebiotic, antimicrobial, and immunomodulatory functions. The authors explore lactoferrin’s dualistic role, both as a selective antimicrobial agent and as a growth enhancer for specific probiotic strains. The review emphasizes the mechanistic insights behind LF’s function in modulating the gut microbiome, supporting probiotic growth, and providing therapeutic benefit in various disease contexts.

Who Was Reviewed?

The review synthesizes data across diverse studies, including in vitro analyses using various probiotic strains, animal models, and clinical trials involving infants, preterm neonates, and adults. The scope of organisms includes Gram-positive and Gram-negative pathogens, commensals, and probiotics, allowing a broad understanding of LF’s selective biological interactions.

What Were the Most Important Findings?

Lactoferrin exhibits a paradoxical yet beneficial role in the microbiome: it selectively inhibits pathogens while preserving or enhancing probiotic viability under certain conditions. Its antimicrobial action stems from iron sequestration and LF-derived peptides like lactoferricin. Importantly, many probiotics, including Lactobacillus and Bifidobacterium species, show resilience to LF’s antibacterial effects, and some even demonstrate enhanced growth in its presence, especially under environmental stress like cold temperatures (e.g., 22°C).

Transcriptomic data reveal that LF modulates central metabolic and stress-response pathways in L. rhamnosus GG, enabling it to thrive under suboptimal conditions. In vivo, LF supplementation has correlated with shifts in microbiota favoring beneficial taxa, including Lactobacillus and Bifidobacterium, and with decreased levels of Enterobacter and Klebsiella. When paired with probiotics, LF exerts synergistic effects, enhancing pathogen suppression and supporting metabolic and immune resilience, especially in models of NAFLD, sepsis, and bacterial vaginosis. These effects are mechanistically linked to LF’s ability to interact with probiotic surface proteins, influence gene expression, and possibly deliver glycan-bound energy substrates.

What Are the Greatest Implications of This Review?

This review highlights lactoferrin as a promising adjunct in microbiome-targeted interventions (MBTIs). Its ability to differentially influence microbial populations, suppressing pathogens while supporting probiotics, makes it uniquely valuable for targeted microbiota modulation. Mechanistic insights suggest that LF can help restore balance in dysbiotic ecosystems, enhance resilience under physiological stress, and synergize with probiotics to improve outcomes in metabolic, infectious, and inflammatory conditions. The findings justify the inclusion of lactoferrin in clinical protocols aiming to manipulate gut flora for therapeutic benefit, especially in vulnerable populations like neonates, obese individuals, and those with infection-prone immune profiles.