Infant Saliva Microbiome Activity Modulates Nutritional Impacts on Neurodevelopment

Neurodevelopment is influenced by complex interactions between environmental factors, including social determinants of health (SDOH), nutrition, and even the microbiome. This longitudinal cohort study of 142 infants tested the hypothesis that microbial activity modulates the effects of nutrition on neurodevelopment. Salivary microbiome activity was measured at 6 months using RNA sequencing. Infant nutrition was assessed longitudinally with the Infant Feeding Practices survey. The primary outcome was presence/absence of neurodevelopmental delay (NDD) at 18 months on the Survey of Wellbeing in Young Children. A logistic regression model employing two microbial factors, one nutritional factor, and two SDOH accounted for 33.3% of the variance between neurodevelopmental groups (p < 0.001, AIC = 77.7). NDD was associated with Hispanic ethnicity (OR 18.1, 2.36–139.3; p = 0.003), no fish consumption (OR 10.6, 2.0–54.1; p = 0.003), and increased Candidatus Gracilibacteria activity (OR 1.43, 1.00–2.07; p = 0.007). Home built after 1977 (OR 0.02, 0.001–0.53; p = 0.004) and Chlorobi activity (OR 0.76, 0.62–0.93, p = 0.001) were associated with reduced risk of NDD. Microbial alpha diversity modulated the effect of fish consumption on NDD (X² = 5.7, p = 0.017). These data suggest the benefits of fish consumption for neurodevelopment may be mediated by microbial diversity. Confirmation in a larger, randomized trial is required.