Long-term benefits of probiotics and calcium supplementation during childhood, and other biomedical and socioenvironmental factors, on adolescent neurodevelopmental outcomes

Abstract

• Probiotics supplementation in childhood improve adolescent neurodevelopment. • The effects of probiotics on neurodevelopment are strain-specific. • Low calcium supplementation resulted in lower BDNF as compared to regular calcium. • Combined childhood interventions with probiotics and socioenvironmental components are warranted. We evaluated the impact of 6-month probiotics and calcium supplementation at 1–6 years of age on neurodevelopment in adolescence, along with the effects of other biomedical and socioenvironmental factors. We re-enrolled 238 adolescents 10-years after supplementation with low-lactose milk with either low calcium (LC; ∼50 mg/d; n = 53), regular calcium (RC; ∼440 mg/d; n = 70), RC with 5x10 8 CFU/d Lactobacillus reuteri DSM17938 (reuteri; n = 55), or RC with 5x10 8 CFU/d L. casei CRL431 (casei; n = 60). Compared to RC, the casei group scored 0.38 SD (effect size, 0.04–0.72) higher on the Raven’s Progressive Matrices; the reuteri group was 0.38 SD (0.01–0.75) lower on the Children’s Depression Inventory; and the LC and younger adolescents in the reuteri group were 0.36 (0.01–0.71) and 0.49 SD (0.02–0.95) lower in brain-derived neurotrophic factor. Diet quality, physical activity, and home environment contributed similar effect sizes. Probiotics supplementation in childhood have strain-specific long-term neurodevelopmental benefits and integration with socioenvironmental interventions are warranted.