Revealing the importance of prenatal gut microbiome in offspring neurodevelopment in humans

It has been widely recognized that a critical time window for neurodevelopment occurs in early life and the host's gut microbiome plays an important role in neurodevelopment. Following recent demonstrations that the maternal prenatal gut microbiome influences offspring brain development in murine models, we aim to explore whether the critical time window for the association between the gut microbiome and neurodevelopment is prenatal or postnatal for human.

Here we leverage a large-scale human study and compare the associations between the gut microbiota and metabolites from mothers during pregnancy and their children with the children's neurodevelopment. Specifically, using multinomial regression integrated in Songbird, we assessed the discriminating power of the maternal prenatal and child gut microbiome for children's neurodevelopment at early life as measured by the Ages & Stages Questionnaires (ASQ).

We show that the maternal prenatal gut microbiome is more relevant than the children's gut microbiome to the children's neurodevelopment in the first year of life (maximum Q² = 0.212 and 0.096 separately using the taxa at the class level). Moreover, we found that Fusobacteriia is more associated with high fine motor skills in ASQ in the maternal prenatal gut microbiota but become more associated with low fine motor skills in the infant gut microbiota (rank = 0.084 and -0.047 separately), suggesting the roles of the same taxa with respect to neurodevelopment can be opposite at the two stages of fetal neurodevelopment.

These findings shed light, especially in terms of timing, on potential therapeutic interventions to prevent neurodevelopmental disorders.

This work was supported by the National Institutes of Health (grant numbers: R01AI141529, R01HD093761, RF1AG067744, UH3OD023268, U19AI095219, U01HL089856, R01HL141826, K08HL148178, K01HL146980), and the Charles A. King Trust Postdoctoral Fellowship.