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

Key PointsThis section will be completed further ImportanceToddlerhood 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 of Limosilactobacillus reuteri DSM 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 of L. reuteri, and higher bifidobacteria presence in the stools of EYCF vs CM children at both 3 and 6 months. Increased L. reuteri abundance 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 as Bifidobacterium spp. and L. reuteri expansion. 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 a L. 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 at clinicaltrial.gov as NCT04799028