Infant microbes and metabolites point to childhood neurodevelopmental disorders

This study has followed a birth cohort for over 20 years to find factors associated with neurodevelopmental disorder (ND) diagnosis. Detailed, early-life longitudinal questionnaires captured infection and antibiotic events, stress, prenatal factors, family history, and more. Biomarkers including cord serum metabolome and lipidome, human leukocyte antigen (HLA) genotype, infant microbiota, and stool metabolome were assessed. Among the 16,440 Swedish children followed across time, 1,197 developed an ND. Significant associations emerged for future ND diagnosis in general and for specific ND subtypes, spanning intellectual disability, speech disorder, attention-deficit/hyperactivity disorder, and autism. This investigation revealed microbiome connections to future diagnosis as well as early emerging mood and gastrointestinal problems. The findings suggest links to immunodysregulation and metabolism, compounded by stress, early-life infection, and antibiotics. The convergence of infant biomarkers and risk factors in this prospective, longitudinal study on a large-scale population establishes a foundation for early-life prediction and intervention in neurodevelopment.
ABIS was supported by Barndiabetesfonden (Swedish Child Diabetes Foundation) ; Swedish Council for Working Life and Social Research grant/award numbers FAS2004-1775 and FAS2004-1775; Swedish Research Council grant/award numbers K2005-72X-11242-11A, K2008-69X-20826-01-4, and K2008-69X-20826-01-4; Östgöta Brandstodsbolag; Medical Research Council of Southeast Sweden (FORSS) ; JDRF Wallenberg Foundation grant/award number K98-99D-12813-01A; ALF and LFoU grants from Region Östergötland and Linköping University, Sweden; and the Joanna Cocozza Foundation. This research was funded by JDRF grant no. 1-INO-2018-637-A-N and supported by the "Inflammation in human early life: targeting impacts on life-course health" (INITIALISE) consortium funded by the Horizon Europe Program of the European Union under grant agreement 101094099.