Partially Hydrolyzed, Whey-Based Infant Formula with Six Human Milk Oligosaccharides, B. infantis LMG11588, and B. lactis CNCM I-3446 is Safe, Well Tolerated, and Improves Gut Health: Staged Analysis of a Randomized Trial

Jean-charles PICAUD^1,2*Olivier CLARIS³Mercedes Gil_Campos⁴Ignacio Salamanca De La Cueva⁵Luc Cornette⁶Philippe Alliet⁷Andre Leke⁸Mireille Castanet⁹Hugues Piloquet¹⁰Virginie de Halleux¹¹DELPHINE MITANCHEZ¹²Yvan Vandenplas¹³Pierre Maton¹⁴Frank Jochum¹⁵Dirk Olbertz¹⁶Sergio Negre Policarpo¹⁷Luca Lavalle¹⁸Cecilia Fumero¹⁸Paula Rodriguez-Garcia¹⁹Janne Marie Moll¹⁹Irma Silva-Zolezzi²⁰Boutaina Zemrani²⁰Nicholas P Hays²⁰Norbert Sprenger¹⁸Javier Miranda-Mallea²¹

• ¹Université Claude Bernard Lyon 1, Lyon, France
• ²Hôpital de La Croix-Rousse, Lyon, France
• ³Hôpital Femme Mère Enfants, Bron, France
• ⁴University of Córdoba, IMIBIC, CIBEROBN, Córdoba, Spain
• ⁵Instituto Hispalense de Pediatria, Sevilla, Spain
• ⁶AZ Sint-Jan Hospital, Brugge, Belgium
• ⁷Jessa Hospital, Hasselt, Belgium
• ⁸Centre Hospitalier Universitaire Amiens Picardie, Amiens, France
• ⁹Rouen University Hospital Charles Nicole, Rouen, France
• ¹⁰Centre Hospitalier Universitaire de Nantes, Nantes, France
• ¹¹Centre Hospitalier Universitaire de Liège, Liège, Belgium
• ¹²Centre Hospitalier Universitaire de Tours, Tours, France
• ¹³Vrije Universiteit Brussel, Brussels, Belgium
• ¹⁴Clinique CHC-Montlégia, Liège, Belgium
• ¹⁵Evangelisches Waldkrankenhaus Spandau, Berlin, Germany
• ¹⁶Klinikum Südstadt Rostock, Rostock, Germany
• ¹⁷Hospital Quironsalud, Valencia, Spain
• ¹⁸Nestlé Research, Lausanne, Switzerland
• ¹⁹Cmbio, Copenhagen, Denmark
• ²⁰Nestlé Product Technology Center – Nutrition, Vevey, Switzerland
• ²¹Hospital Vithas, Valencia, Spain

Background and aims: Gut health and microbiome development are closely linked in early life, with human milk oligosaccharides (HMOs) playing a key role. Here, we report results through age 4 months of a trial evaluating infant formula containing a synbiotic blend of HMOs and probiotics on growth, gastrointestinal (GI) tolerance, and gut health biomarkers from birth to 15 months.Methods: Healthy infants aged ≤14 days were randomized to experimental (SYN; control formula plus 6 HMOs and two probiotics [B. infantis, B. lactis]) or control formula (CTRL; partially hydrolyzed 100% whey-based formula). Non-randomized breastfed (BF) infants served as a reference group. The primary endpoint was weight gain velocity in SYN vs. CTRL through 4 months. Secondary endpoints included fecal outcomes (Bifidobacterium abundance, immune and gut health markers), GI tolerance, and adverse events (AEs).Results: There were 313 infants in the full analysis set (FAS; 118 SYN, 114 CTRL, 81 BF), and 227 in the per-protocol population (PP; 84, 84, 59, respectively). Weight gain velocity through 4 months in SYN was non-inferior to CTRL in both FAS and PP (both p<0.0001). Parent-reported GI tolerance and stooling patterns were similar in SYN and CTRL through 4 months. Bifidobacterium abundance at 3 months was higher in SYN vs. CTRL (p=0.004). Fecal pH in SYN was lower than CTRL (p=0.018) and closer to BF at 3 months, while immune and gut health markers were similar between SYN and BF. No significant differences in AEs were observed.Conclusion: The synbiotic-supplemented infant formula supported healthy, age-appropriate growth, good GI tolerance, and an increased abundance of beneficial Bifidobacterium through age 4 months.