Laurent Béghin1, Sebastian Tims2, Mieke Roelofs3, Carole Rougé4, Raish Oozeer3, Thameur Rakza5, Gaetano Chirico6, Guus Roeselers3, Jan Knol7, Jean Christophe Rozé8, Dominique Turck9. 1. Univ. Lille, CHU Lille, Clinical Investigation Center, CIC-1403-Inserm-CHU and U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000, Lille, France. 2. Danone Nutricia Research, Utrecht, the Netherlands. Electronic address: sebastian.tims@danone.com. 3. Danone Nutricia Research, Utrecht, the Netherlands. 4. Laboratoire Gallia, Limonest, France. 5. Department of Neonatology, Lille University Jeanne de Flandre Children's Hospital and Faculty of Medicine, University of Lille, F-59000, Lille, France. 6. Department of Neonatology, Spedali Civili, Brescia, Italy. 7. Danone Nutricia Research, Utrecht, the Netherlands; Laboratory of Microbiology, Wageningen University, the Netherlands. 8. Department of Neonatal Medicine, Nantes University Hospital, Nantes, France. 9. Univ. Lille, CHU Lille, Clinical Investigation Center, CIC-1403-Inserm-CHU and U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000, Lille, France; Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Lille University Jeanne de Flandre Children's Hospital and Faculty of Medicine, University of Lille, F-59000, Lille, France.
Abstract
BACKGROUND & AIMS: Microbiome-modulators can help positively steer early-life microbiota development but their effects on microbiome functionality and associated safety and tolerance need to be demonstrated. We investigated the microbiome impact of a new combination of bioactive compounds, produced by the food-grade microorganisms Bifidobacterium breve C50 and Streptococcus thermophilus ST065 during a fermentation process, and prebiotics in an infant formula. Tolerance and safety were also assessed. METHODS: An exploratory prospective, randomized, double-blind, controlled, multi-centre study was designed to investigate the effect of bioactive compounds and prebiotics (short-chain galacto-oligosaccharides (scGOS)/long-chain fructo-oligosaccharides (lcFOS) 9:1). Experimental formulas containing these bioactive compounds and prebiotics (FERM/scGOS/lcFOS), prebiotics (scGOS/lcFOS), or bioactive compounds (FERM), were compared to a standard cow's milk-based control formula (Control). Exclusively breastfed infants were included as a reference arm since exclusive breastfeeding is considered as the optimal feeding for infants. The study lasted six months and included visits to health care professionals at baseline, two, four and six months of age. Stool SIgA concentration was the primary study outcome parameter. RESULTS: There were 280 infants randomized over the experimental arms and 70 infants entered the breastfed-reference arm. Demographics were balanced, growth and tolerance parameters were according to expectation and adverse events were limited. At four months of age the median SIgA concentration in the FERM/scGOS/lcFOS group was significantly higher compared to the Control group (p = 0.03) and was more similar to the concentrations found in the breastfed-reference group. Bifidobacterium increased over time in all groups. The FERM/scGOS/lcFOS combination resulted in a microbiota composition and metabolic activity closer to the breastfed infants' microbiome. CONCLUSION: The FERM/scGOS/lcFOS combination showed a significant positive effect on SIgA levels. All formulas tested were associated with normal growth and were well-tolerated. Additionally, at four months of age the FERM/scGOS/lcFOS formula brought the microbiome composition and metabolic activity closer towards that of breastfed infants. CLINICAL TRIAL REGISTRY: Registration number NTR2726 (Netherlands Trial Register; www.trialregister.nl/).
RCT Entities:
BACKGROUND & AIMS: Microbiome-modulators can help positively steer early-life microbiota development but their effects on microbiome functionality and associated safety and tolerance need to be demonstrated. We investigated the microbiome impact of a new combination of bioactive compounds, produced by the food-grade microorganisms Bifidobacterium breve C50 and Streptococcus thermophilus ST065 during a fermentation process, and prebiotics in an infant formula. Tolerance and safety were also assessed. METHODS: An exploratory prospective, randomized, double-blind, controlled, multi-centre study was designed to investigate the effect of bioactive compounds and prebiotics (short-chain galacto-oligosaccharides (scGOS)/long-chain fructo-oligosaccharides (lcFOS) 9:1). Experimental formulas containing these bioactive compounds and prebiotics (FERM/scGOS/lcFOS), prebiotics (scGOS/lcFOS), or bioactive compounds (FERM), were compared to a standard cow's milk-based control formula (Control). Exclusively breastfed infants were included as a reference arm since exclusive breastfeeding is considered as the optimal feeding for infants. The study lasted six months and included visits to health care professionals at baseline, two, four and six months of age. Stool SIgA concentration was the primary study outcome parameter. RESULTS: There were 280 infants randomized over the experimental arms and 70 infants entered the breastfed-reference arm. Demographics were balanced, growth and tolerance parameters were according to expectation and adverse events were limited. At four months of age the median SIgA concentration in the FERM/scGOS/lcFOS group was significantly higher compared to the Control group (p = 0.03) and was more similar to the concentrations found in the breastfed-reference group. Bifidobacterium increased over time in all groups. The FERM/scGOS/lcFOS combination resulted in a microbiota composition and metabolic activity closer to the breastfed infants' microbiome. CONCLUSION: The FERM/scGOS/lcFOS combination showed a significant positive effect on SIgA levels. All formulas tested were associated with normal growth and were well-tolerated. Additionally, at four months of age the FERM/scGOS/lcFOS formula brought the microbiome composition and metabolic activity closer towards that of breastfed infants. CLINICAL TRIAL REGISTRY: Registration number NTR2726 (Netherlands Trial Register; www.trialregister.nl/).