Background/Objectives: Lactoferrin, a key bioactive component in human milk, may bridge functional gaps in infant formula; however, its long-term effects on growth and the gut microbiota in term infants remain underexplored, particularly in real-world settings. Methods: This real-world evidence (RWE) study assessed the impact of lactoferrin-fortified formula (LF) on infant growth, the gut microbiota, and feeding tolerance compared with control formula (CF) and exclusive breastfeeding (BF). After propensity score matching (PSM) for maternal education level and infant age, 111 matched Chinese infants (37 per group: LF, CF, and BF; age: 6–12 months) were analyzed. Growth was evaluated using WHO Z-scores (WAZ, LAZ, WLZ, and zBMI). The gut microbiota was profiled via 16S rRNA sequencing (n = 81). Feeding challenges were quantified using the Montreal Children’s Hospital Feeding Scale (MCH-FS). Results: The LF group exhibited significantly higher length-for-age Z-scores (LAZ) compared with both the BF and CF groups (p < 0.001), indicating superior linear growth. LF infants also showed reduced MCH-FS scores (18.0 vs. 36.2 in CF; p < 0.001), signifying fewer feeding difficulties. Gut microbiota analysis revealed enrichment of Bifidobacterium breve and butyrate-producing taxa (e.g., Faecalibacterium and Ruminococcaceae), higher alpha diversity, and metabolic divergence, involving enhanced lysine fermentation to acetate/butyrate in LF infants, suggesting a higher level of short-chain fatty acid (SCFA) production. Beta diversity analysis demonstrated that the LF microbiota clustered close to BF. Conclusions: Lactoferrin-fortified formula was associated with improved linear growth and feeding tolerance while shaping a healthy gut microbiota, showing similarities to breastfed infants’ microbiota. These findings support LF fortification as a strategy to improve functional outcomes in formula-fed infants.
Shi et al. (Fri,) studied this question.