The Relationship Between the Preterm Infant Gut Microbiome and Later Childhood Behavior

Abstract Background and Objectives Very Low Birth Weight (VLBW) infants, born weighing less than 1500 grams, are at risk for both gut dysbiosis and later neuropsychological developmental deficits. With gut dysbiosis there is a disequilibrium of the gut microbial community. The Gammaproteobacteriadominated gut dysbiosis in VLBW infants likely results from a combination of immaturity derived from interrupted intrauterine development and environmental exposures in the Neonatal Intensive Care Unit (NICU) after birth. The extent of later neurobehavioral consequences associated with such microbial dysbiosis have yet to be determined. Methods We explored associations between the infants’ gut microbiome richness, diversity, composition, and network and early childhood behavior at 2 and 4 years of age in 25 children who were previously preterm born and studied while hospitalized in the Neonatal Intensive Care Unit (NICU). Behavior was measured with the Child Behavior Checklist (CBCL) at home visits at 32.2+/-4.8 months, and again at 49 +-3.6 months. We also measured children’s microbiomes at 2 and 4 years of age. Results The diversity and richness of the gut microbiome in VLBW infants were associated with later parent-reported maladaptive behavioral and emotional symptoms, including symptoms associated with autism, anxiety, Attention-Deficit/Hyperactivity Disorder (ADD), attention problems, and aggressive behavior. Microbiome compositional signatures were also associated with later childhood behavior. Network analysis revealed that the microbiome networks differed in the children at 2 and 4 years of age and different amplicon sequence variants (ASVs) were associated with behavior at these timepoints. Conclusions These data provide preliminary support for relationships between both the VLBW and later child gut microbiome dysbiosis and childhood behavior.