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Early Effect of Supplemented Infant Formulae on Intestinal Biomarkers and Microbiota: A Randomized Clinical Trial

CIC INSERM U1404, Department of Pediatric, Rouen University Hospital Charles Nicolle, 76031 Rouen, France
Department of Neonatology, Alexandra Regional General Hospital, 11528 Athens, Greece
Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
Department of Neonatology, Maternite Regionale, CHRU Nancy, 54035 Nancy, France
Nestlé Research, Société des Produits Nestlé S.A., 1000 Lausanne, Switzerland
SBU Nutrition, Nestlé, 1800 Vevey, Switzerland
Nestlé Health Science, 1066 Epalinges, Switzerland
Department of Neonatology, University Hospital Croix Rousse, Hospices Civils de Lyon, 69317 Lyon France
INSERM U1060, INRA U1397, Claude Bernard University Lyon 1, Lyon, 69100 Villeurbanne, France
Author to whom correspondence should be addressed.
Nutrients 2020, 12(5), 1481;
Received: 20 April 2020 / Revised: 11 May 2020 / Accepted: 16 May 2020 / Published: 20 May 2020
(This article belongs to the Section Prebiotics and Probiotics)
Background: Post-natal gut maturation in infants interrelates maturation of the morphology, digestive, and immunological functions and gut microbiota development. Here, we explored both microbiota development and markers of gut barrier and maturation in healthy term infants during their early life to assess the interconnection of gut functions during different infant formulae regimes. Methods: A total of 203 infants were enrolled in this randomized double-blind controlled trial including a breastfed reference group. Infants were fed starter formulae for the first four weeks of life, supplemented with different combination of nutrients (lactoferrin, probiotics (Bifidobacterium animal subsp. Lactis) and prebiotics (Bovine Milk-derived Oligosaccharides—BMOS)) and subsequently fed the control formula up to eight weeks of life. Stool microbiota profiles and biomarkers of early gut maturation, calprotectin (primary outcome), elastase, α-1 antitrypsin (AAT) and neopterin were measured in feces at one, two, four, and eight weeks. Results: Infants fed formula containing BMOS had lower mean calprotectin levels over the first two to four weeks compared to the other formula groups. Elastase and AAT levels were closer to levels observed in breastfed infants. No differences were observed for neopterin. Global differences between the bacterial communities of all groups were assessed by constrained multivariate analysis with hypothesis testing. The canonical correspondence analysis (CCA) at genus level showed overlap between microbiota profiles at one and four weeks of age in the BMOS supplemented formula group with the breastfed reference, dominated by bifidobacteria. Microbiota profiles of all groups at four weeks were significantly associated with the calprotectin levels at 4 (CCA, p = 0.018) and eight weeks of age (CCA, p = 0.026). Conclusion: A meaningful correlation was observed between changes in microbiota composition and gut maturation marker calprotectin. The supplementation with BMOS seems to favor gut maturation closer to that of breastfed infants. View Full-Text
Keywords: early gut maturation; infant microbiota; probiotics; prebiotics early gut maturation; infant microbiota; probiotics; prebiotics
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MDPI and ACS Style

Castanet, M.; Costalos, C.; Haiden, N.; Hascoet, J.-M.; Berger, B.; Sprenger, N.; Grathwohl, D.; Brüssow, H.; De Groot, N.; Steenhout, P.; Pecquet, S.; Benyacoub, J.; Picaud, J.-C. Early Effect of Supplemented Infant Formulae on Intestinal Biomarkers and Microbiota: A Randomized Clinical Trial. Nutrients 2020, 12, 1481.

AMA Style

Castanet M, Costalos C, Haiden N, Hascoet J-M, Berger B, Sprenger N, Grathwohl D, Brüssow H, De Groot N, Steenhout P, Pecquet S, Benyacoub J, Picaud J-C. Early Effect of Supplemented Infant Formulae on Intestinal Biomarkers and Microbiota: A Randomized Clinical Trial. Nutrients. 2020; 12(5):1481.

Chicago/Turabian Style

Castanet, Mireille, Christos Costalos, Nadja Haiden, Jean-Michel Hascoet, Bernard Berger, Norbert Sprenger, Dominik Grathwohl, Harald Brüssow, Nanda De Groot, Philippe Steenhout, Sophie Pecquet, Jalil Benyacoub, and Jean-Charles Picaud. 2020. "Early Effect of Supplemented Infant Formulae on Intestinal Biomarkers and Microbiota: A Randomized Clinical Trial" Nutrients 12, no. 5: 1481.

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