Infant gut microbiomes contribute to metabolic states that impact brain function

Midani, F. S.; Lee, D.-H.; Moon, Y.; Seale, M.; Horvath, T. D.; Ardis, A. K.; Cantu, J.; Coles, E.; Pizzini, J. D.; Zhu, D.; Dooling, S. W.; Ahern, G. J.; Ardis, C. K.; Beckford, A.; Ruggiero, N. M.; Shin, J.; Joos, R.; Stanton, C.; Ross, R. P.; Dai, D. D. L.; Mandhane, P. J.; Petersen, C.; Turvey, S. E.; Kiely, M. E.; Murray, D. M.; Costa-Mattioli, M.; Tolias, K. F.; Britton, R. A.; Danhof, H. A.

doi:10.64898/2026.03.09.710596

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bioRxiv · 10.64898/2026.03.09.710596

Infant gut microbiomes contribute to metabolic states that impact brain function

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Abstract

Alterations in the gut microbiome are associated with neurodevelopmental disorders, but causal mechanisms and therapeutic strategies remain undefined. Here, we demonstrate that human infant microbiomes isolated during the first six months of life drive behavioral impairments in mice and that microbiota-based interventions restore mice to normal behavior. Early-life microbiomes from twelve infants who later exhibited cognitive deficits at 2 years old (low-scoring) transferred adverse metabolic, brain, and behavioral phenotypes to mice, in contrast to microbiomes from twenty-three cognitively typical or high-scoring infants. Deficits in mice were rescued by fecal microbiota transplant from high-scoring infants or a rationally designed consortium that promoted amino acid levels. We confirmed lower fecal amino acid concentrations in low-scoring infants and replicated the association between early-life microbiome composition and cognitive outcomes in a second geographically independent infant cohort. Altogether, we discovered an early-life microbiome-mediated metabolic state causally linked to cognitive deficits and amenable to microbial intervention.

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Midani, F. S., Lee, D.-H., Moon, Y., Seale, M., Horvath, T. D., Ardis, A. K., Cantu, J., Coles, E., Pizzini, J. D., Zhu, D., Dooling, S. W., Ahern, G. J., Ardis, C. K., Beckford, A., Ruggiero, N. M., Shin, J., Joos, R., Stanton, C., Ross, R. P., Dai, D. D. L., Mandhane, P. J., Petersen, C., Turvey, S. E., Kiely, M. E., Murray, D. M., Costa-Mattioli, M., Tolias, K. F., Britton, R. A., Danhof, H. A.. 2026-03-10. Infant gut microbiomes contribute to metabolic states that impact brain function. https://doi.org/10.64898/2026.03.09.710596

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