Effects of an infant formula containing a whey protein concentrate on feeding tolerance and markers of intestinal immune defense in Chinese infants

Abstract Background Human milk (HM) bioactive components can have immune modulatory functions, impact the gut microbiome, and may result in functional benefits when added to infant formula (IF). In this single-arm, prospective, intervention study, we tested the effectiveness of an IF with a whey protein concentrate co-enriched in α-lactalbumin, milk fat globule membrane (MFGM), and Sn-2 palmitate resulting in protein and lipid profiles observed in HM. The outcomes tested were feeding tolerance, Bifidobacteria abundance, and intestinal and immune health of Chinese infants. Methods Predominantly formula-fed (FF) and breastfed (BF) infants were enrolled between 3 and 28 days and assigned to the FF (N= 60) or BF (N=60) group, per their feeding practice, for 6 weeks. The primary endpoint was Infant Gastrointestinal Symptom Questionnaire (IGSQ) index score assessed using a validated IGSQ-13 questionnaire after 6 weeks of intervention; non-inferiority of FF vs BF was tested. Secondary endpoints included fecal Bifidobacteria abundance assessed using shotgun metagenomics sequencing; fecal short chain fatty acids (SCFAs) analyzed by ultra-performance liquid chromatography-tandem mass spectrometry; fecal markers of immune response, inflammation, intestinal barrier integrity (secretory immunoglobulin A sIgA), cytokines, calprotectin, α1 antitrypsin, lipocalin-2) assessed using enzyme-linked immunosorbent assay; stool consistency assessed using gastrointestinal (GI) diary; anthropometric assessments; quality of life; physician reported adverse events; and use of medications. Results Good GI tolerance was observed in both groups at V2 (mean±SD IGSQ score FF: 19.9±7.4; BF: 16.8±4.2); difference of means 1.35 [95% CI: -1.312, 4.012]). After 6 weeks, Bifidobacterium genus relative abundance was not significantly different between the groups. Total SCFAs were significantly higher (p<0.05) in the FF versus BF group, driven by increased levels of valeric and propanoic acids (p<0.05 for both). The IGSQ domain scores, stool consistency, fecal markers of immunity, inflammation, and intestinal barrier integrity (except lipocalin-2 which was significantly higher in BF vs FF), anthropometric Z-scores, common illnesses, antibiotic use, and adverse events were not significantly different between groups at week 6. Conclusions Our results support the effectiveness of this tested infant formula in supporting good GI tolerance, growth, specific intestinal and immune health markers, and Bifidobacteria abundance similar to that of the BF group. Trial registration NCT04880083 (2021-05-06)