Prebiotic and modulatory evidence of lactoferrin on gut health and function Original paper

What was reviewed?

This review comprehensively examined the structure, mechanisms, and functional role of lactoferrin (LF) in gut health, with a strong emphasis on its prebiotic effects, immune modulation, gut barrier integrity, and anti-pathogenic activity. The authors synthesized findings from in vitro, in vivo, and clinical studies to present LF as a multifaceted intervention for modulating the intestinal microbiota, suppressing inflammation, and supporting host immunity.

Who was reviewed?

The review included data from a broad range of models: human clinical trials, animal studies (mice, rats, piglets, zebrafish), and cell cultures (Caco-2, IPEC-J2, HT-29, macrophage lines). It also encompassed microbial interaction studies with Gram-positive and Gram-negative bacteria, viruses, and protozoa to assess the antimicrobial and immunological effects of LF.

Most Important Findings

Lactoferrin exhibits potent immunomodulatory effects and serves as a dual-function agent, simultaneously suppressing enteric pathogens and promoting beneficial microbial taxa such as Bifidobacterium and Lactobacillus species while suppressing Enterobacteriaceae, E. coli O157:H7, and Salmonella. It may serve as a potent microbiota-shaping agent in dysbiotic conditions.

LF reduces intestinal inflammation by modulating pro-inflammatory cytokines and enhancing anti-inflammatory mediators like IL-10. LF also reinforces gut barrier integrity by upregulating tight junction proteins (Claudin-1, Occludin, ZO-1) and restoring epithelial morphology in models of colitis and inflammatory damage. Notably, in both its apo- (iron-depleted) and holo- (iron-saturated) forms, LF inhibits adhesion and proliferation of pathogens such as E. coli, Salmonella, Shigella, and Staphylococcus aureus, often through iron sequestration or membrane disruption.

LF and its peptide derivatives—lactoferricin and lactoferrampin, enhance gut immunity and exhibit higher antimicrobial activity than the intact protein. LF has also been shown to modulate Toll-like receptor (TLR) signaling and gut microbiota composition disrupted by antibiotics. Clinical studies revealed its efficacy in reducing diarrhea, improving iron absorption without gastrointestinal side effects, and lowering the risk of sepsis in neonates.

What Are the Implications of This Review?

Lactoferrin’s ability to modulate both host immunity and microbial communities establishes it as a promising natural therapeutic or adjunct intervention for gut-related conditions, including colitis, infections, and colorectal cancer. Its compatibility with probiotic therapies and its low side-effect profile make it a compelling candidate for both preventative and therapeutic applications. LF’s prebiotic classification is increasingly supported by mechanistic insights, including direct microbial interactions and epithelial barrier restoration. This positions lactoferrin as a valuable clinical tool in microbiome-targeted interventions, particularly in patients with inflammatory bowel disorders, antibiotic-induced dysbiosis, and vulnerable populations such as infants and immunocompromised individuals.