Lactoferrin combined with Bifidobacterium animalis subsp. lactis BB-12 improves respiratory tract infections and modulates Gut microbiome function in children: a randomized, double-blind, placebo-controlled trial.

OBJECTIVES AND STUDY: To explore the effects and mechanisms of lactoferrin combined with Bifidobacterium animalis subsp. lactis BB-12 on Respiratory tract infections (RTIs) in healthy children through a randomized, double-blind, placebo-controlled trial.

METHODS

Eligible healthy children aged 0-6 years were randomized into intervention group (IG, n = 60, receiving lactoferrin and probiotic for 3 months) and control group (CG, n = 34, receiving placebo). The study primarily assessed changes in the incidence and severity of RTIs, and monitored gastrointestinal adverse events. Fecal samples were collected pre- and post-intervention to analyze gut microbiota composition and metabolomic profiles, including short-chain fatty acids (SCFAs).

RESULTS

After the intervention, the incidence of RTIs showed no significant difference between groups (55% vs. 61.8%, p = 0.52), but both the RTI severity score (3.0 vs. 4.0, p < 0.05) and mean duration per RTI episode (3.54 d vs. 5.27 d, p < 0.05) were significantly lower in the IG. No serious adverse events were reported, and the incidence of indigestion was significantly reduced in the IG compared with the CG (8.3% vs. 23.5%, p = 0.04). The intervention significantly altered phylogenetic diversity (PD-whole tree within IG: p = 0.0011; baseline between IG and CG: p = 0.63; post-intervention between IG and CG: p = 0.029) and community structure (weighted UniFrac within IG: 0.012; between IG and CG at 3 months: p = 0.036 vs. baseline p = 0.01). The gut microbiota in the intervention group exhibited a trend toward greater stability over time. Integrated microbiome-metabolite analysis showed attenuation of fatty acid oxidation-and energy metabolism-related metabolic drivers after intervention, together with no significant changes in fecal SCFA levels.

CONCLUSIONS

The intervention improved clinical outcomes and induced phylogenetic restructuring of the gut microbiota rather than changes in overall abundance, accompanied by a shift toward greater stability in gut microbial structure and energy metabolic patterns.

CLINICAL TRIAL REGISTRATION: identifier ChiCTR2500111308.