Lactoferrin: a secret weapon in the war against pathogenic bacteria Original paper

What Was Reviewed?

This definitive review meticulously examined the antimicrobial properties of lactoferrin (Lf), a cationic glycoprotein integral to the innate immune system, and its potential as a therapeutic weapon against pathogenic bacteria—particularly in the face of escalating antimicrobial resistance. The authors delved into Lf’s multifaceted mechanisms of action, which include iron sequestration to starve bacteria, direct disruption of bacterial membranes leading to lysis, and the generation of potent antimicrobial peptides like lactoferricins (Lfcins) and lactoferrampin (Lfampin). The review also explored Lf’s ability to neutralize bacterial virulence factors, such as lipopolysaccharides (LPS), secretion systems, and biofilms, across a diverse range of Gram-positive and Gram-negative bacteria. Additionally, it highlighted Lf’s synergistic potential with antibiotics, positioning it as a promising adjuvant in antimicrobial therapies. By synthesizing evidence from in vitro, in vivo, and clinical studies, the review underscored Lf’s versatility and safety, emphasizing its approval as a dietary supplement and its accessibility for clinical use.

Who Was Reviewed?

The review encompassed a broad spectrum of studies investigating lactoferrin’s antibacterial activity, primarily focusing on in vitro experiments with clinically relevant bacterial species. Key pathogens included Escherichia coli (notably enteropathogenic E. coli [EPEC] and enteroaggregative E. coli [EAEC]), Salmonella Typhimurium, Klebsiella pneumoniae, Pseudomonas aeruginosa, Streptococcus mutans, Streptococcus pneumoniae, and Helicobacter pylori, among others. It also included research on Lf’s effects on bacterial virulence mechanisms, such as biofilm formation and secretion systems, as well as studies exploring its synergistic potential with antibiotics. While the review emphasized laboratory findings, it also touched upon the clinical applications of bovine Lf (bLf), which has been approved as a dietary supplement, highlighting its relevance for both human and veterinary medicine.

What Were the Most Important Findings?

The review conclusively demonstrated that lactoferrin (Lf) and its derived peptides exhibit broad-spectrum antimicrobial and anti-biofilm activity against a wide array of pathogenic bacteria, significantly impacting microbiome-relevant taxa. Specific targets include Escherichia coli, Salmonella Typhimurium, Klebsiella pneumoniae, Pseudomonas aeruginosa, Streptococcus mutans, Streptococcus pneumoniae, Streptococcusagalactiae (GBS) and Helicobacter pylori, alongside others like Bacteroides fragilis and Bacteroides thetaiotaomicron, which are notable in gut microbiota contexts. Lf’s mechanisms extend beyond iron sequestration to include direct membrane disruption, inhibition of bacterial adhesion to host cells, and suppression of biofilm formation—a critical factor in chronic infections and dysbiosis. For instance, Lf disrupts biofilms in P. aeruginosa, S. pneumoniae, and S. mutans, key players in microbiome imbalance. It also impairs virulence by targeting secretion systems and proteases in pathogens like H. pylori and Porphyromonas gingivalis. Although not directly focused on microbiome signatures, Lf’s ability to modulate bacterial communities—particularly by inhibiting pathogens and biofilms—suggests a pivotal role in maintaining microbial balance in mucosal sites like the gut and oral cavity, reinforced by its presence in breast milk and potential influence on infant microbiome development.

What Are the Greatest Implications of this Review?

The review firmly establishes lactoferrin (Lf) as a versatile, nontoxic therapeutic agent with profound implications for combating antimicrobial resistance, offering clinicians a robust alternative or adjuvant to conventional antibiotics. Its broad-spectrum activity against multidrug-resistant bacteria, without reported resistance development, positions Lf as a critical tool for managing infections where traditional therapies falter. For clinicians focused on microbiome health, Lf’s capacity to inhibit biofilms and virulence factors in pathogens like Pseudomonas aeruginosa and Streptococcus pneumoniae suggests it could restore microbial equilibrium in dysbiotic states, such as in the gut or oral cavity. Its safety, affordability, and regulatory approval as a dietary supplement enhance its clinical accessibility for prevention and treatment. Future research into Lf’s specific impacts on microbiome signatures and potential synergies with probiotics could further amplify its utility, bridging microbiome research with practical therapeutic applications.