A YOUNG CHILD FORMULA SUPPLEMENTED WITH L. REUTERI AND GALACTO-OLIGOSACCHARIDES MODULATES THE COMPOSITION AND FUNCTION OF THE GUT MICROBIOME SUPPORTING BONE AND MUSCLE DEVELOPMENT IN TODDLERS
Authors: Bonnet Nicolas , Capeding Maria Rosario , Siegwald Léa , Garcia-Garcera Marc , Desgeorges Thibaut , Tytgat Hanne L.P. , Krattinger Laura-Florina , Lebumfacil Jowena , Phee Loudhie Cyd , Moll Janne Marie , Gudjonsson Alexander , Rodriguez-Garcia Paula , Feige Jerome N , Jankovic Ivana , Chen Yipu , Egli Delphine , Horcajada Marie-Noëlle 
Published: December 2024

AbstractKey PointsThis section will be completed furtherImportanceToddlerhood is a key window of opportunity for development of musculoskeletal system and microbiome. In this study we tested the efficacy of a synbiotic-based young child formula on bone and muscle strength and microbiome maturation in young children during motor-skill development.InterventionIn this randomized, double-blind controlled trial, children aged 2-3 years received either an experimental young child formula (EYCF) containing a combination ofLimosilactobacillus reuteriDSM 17938 and galacto-oligosaccharides (GOS) or a minimally fortified milk (CM) for 6 months. A third arm remained on their habitual diet.Main outcomes and measuresBone quality (tibia speed of sound), muscle strength (handgrip), microbiota composition (shotgun metagenomics) and functionality (fecal metabolome) were evaluated at baseline, and after 3 months and 6 months of intervention. Microbiota and metabolomic features were associated to each other and to clinical bone and muscle readouts at the same timepoints.ResultsTibial speed of sound was significantly increased after 6 months (primary end point, p<0.01) and 3 months (p<0.05) of EYCF vs CM feeding. These effects on bone strength were paralleled by significantly higher muscle strength after 6 months in EYCF vs CM. The intervention significantly remodeled microbiome composition, with enrichment ofL. reuteri, and higher bifidobacteria presence in the stools of EYCF vs CM children at both 3 and 6 months. IncreasedL. reuteriabundance after 6 months of EYCF consumption was associated with higher bone quality and muscle strength. Stool metabolomics were significantly modulated by EYCF consumption with 45 metabolites significantly modified and associated to microbiome compositional changes such asBifidobacteriumspp. andL. reuteriexpansion. Pairing of metagenomic and metabolomic signatures induced by EYCF revealed an enrichment of tryptophane and indole metabolism which significantly associated to bone and muscle strength clinical outcomes.Conclusions and relevanceConsumption of an experimental young child formula containing aL. reuteri+ GOS synbiotic improves musculoskeletal development in toddlers that was associated with a modulation of microbiota composition and functionality. These results provide novel mechanistic insights on gut-musculoskeletal crosstalk during early life and demonstrate that nutritional interventions targeting the microbiome can support healthy bone and muscle development and may contribute to functional motorskills acquisition during childhood.Trial registrationThe trial was registered atclinicaltrial.govasNCT04799028