A young child formula with Limosilactobacillus reuteri and GOS modulates gut microbiome and enhances bone and muscle development: a randomized trial

In this randomized, double-blind controlled trial, 182 Filipino 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; n = 91) or a minimally fortified milk (CM; n = 91) for 6 months. Primary outcome was tibia speed of sound and secondary outcomes were muscle strength, blood vitamin D levels, bone turnover markers, gut microbiota, fecal calcium fatty acid soaps and gastro-intestinal tolerance. Compared to CM, those in the EYCF group showed increased tibia speed of sound after 3 and 6 months. The intervention remodeled the stool microbiome composition, assessed by shotgun metagenomics, with enrichment of L. reuteri and higher bifidobacteria presence in the EYCF group. Increased L. reuteri abundance after 6 months of EYCF consumption associates with higher bone quality and muscle strength. Stool metabolomics show 45 metabolites modulated by EYCF consumption and associated to microbiome compositional changes, leading to enrichment of tryptophane and indole metabolism. In summary, consumption of EYCF containing a L. reuteri + GOS synbiotic improves musculoskeletal development in toddlers via modulation of microbiota composition and function. These results provide insights on gut-musculoskeletal crosstalk during early life. Clinicaltrial.gov NCT04799028.