Safety and efficacy of a probiotic-containing infant formula supplemented with 2\u2019-fucosyllactose: a double-blind randomized controlled trial

Philippe Alliet,Sabine N J Jespers,Stefaan Peeters,Jean-Philippe Stalens,Colin I Cercamondi,Norbert Sprenger,Giovanni Corsello,Guus A M Kortman,Bernard Berger,Paola Roggero,Mailis Amico,Yvan Vandenplas

doi:10.1186/s12937-022-00764-2

Abstract

BackgroundHuman milk oligosaccharides (HMOs) have important and diverse biological functions in early life. This study tested the safety and efficacy of a starter infant formula containing Limosilactobacillus (L.) reuteri DSM 17938 and supplemented with 2’-fucosyllactose (2’FL).MethodsHealthy infants < 14 days old (n = 289) were randomly assigned to a bovine milk-based formula containing L. reuteri DSM 17938 at 1 × 107 CFU/g (control group; CG) or the same formula with added 1.0 g/L 2’FL (experimental group; EG) until 6 months of age. A non-randomized breastfed group served as reference (BF; n = 60). The primary endpoint was weight gain through 4 months of age in the formula-fed infants. Secondary endpoints included additional anthropometric measures, gastrointestinal tolerance, stooling characteristics, adverse events (AEs), fecal microbiota and metabolism, and gut immunity and health biomarkers in all feeding groups.ResultsWeight gain in EG was non-inferior to CG as shown by a mean difference [95% CI] of 0.26 [-1.26, 1.79] g/day with the lower bound of the 95% CI above the non-inferiority margin (-3 g/day). Anthropometric Z-scores, parent-reported stooling characteristics, gastrointestinal symptoms and associated behaviors, and AEs were comparable between formula groups. Redundancy analysis indicated that the microbiota composition in EG was different from CG at age 2 (p = 0.050) and 3 months (p = 0.052), approaching BF. Similarly, between sample phylogenetic distance (weighted UniFrac) for BF vs EG was smaller than for BF vs CG at 3-month age (p = 0.045). At age 1 month, Clostridioides difficile counts were significantly lower in EG than CG. Bifidobacterium relative abundance in EG tracked towards that in BF. Fecal biomarkers and metabolic profile were comparable between CG and EG.ConclusionL. reuteri-containing infant formula with 2’FL supports age-appropriate growth, is well-tolerated and may play a role in shifting the gut microbial pattern towards that of breastfed infants.Trial RegistrationThe trial was registered on ClinicalTrials.gov (NCT03090360) on 24/03/2017.

Highlights

Human milk oligosaccharides (HMOs) have important and diverse biological functions in early life
Study Subjects A total of 289 formula-fed infants were randomized to experimental group (EG) (n = 144) and control group (CG) (n = 145) and 60 infants were enrolled into breastfed reference group (BF) (Fig. 1)
A higher proportion of delivery via Caesarian-section and lower proportion of mothers completing college was found among formula-fed infants compared to BF

Summary

Introduction

Human milk oligosaccharides (HMOs) have important and diverse biological functions in early life. Mature breast milk contains approximately 5–20 g/L HMOs of > 160 different known structures [1, 2]. HMOs play diverse and important roles in the development of infants. They have been shown to support the establishment and maintenance of a balanced gut microbiota, a key factor in the development of the mucosal immune system [2]. HMOs may play an important role in immune protection by providing anti-adhesive antimicrobial effects, regulating intestinal epithelial cell response, and modulating immune response via direct effects on immune cell populations and cytokine secretion [2,3,4]. Preclinical and observational data suggests potential beneficial effects of HMOs on brain development [5, 6]

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