Background: Neonatal exposure to antibiotics, in the absence of infection, results in abnormal learning and memory in animals and is linked to changes in gut microbes. The relevance of early-life antibiotic exposure to brain function in humans is not known. Methods: Recognition memory was assessed at 1 month of age in 15 term-born infants exposed to antibiotics (with negative cultures) and 57 unexposed infants using event-related potentials (ERPs). Linear regression analysis, adjusting for covariates, was employed to compare groups with respect to ERP features representing early stimulus processing (P2 amplitude) and discrimination between mother and stranger voices. Results: Infants exposed to antibiotics exhibited smaller P2 amplitudes for both voice conditions (p = 0.001), with greatest reductions observed for mother’s voice in frontal and central scalp regions (p < 0.04). Infants exposed to antibiotics showed larger P2 amplitudes to stranger’s as compared to mother’s voice, a reversal of the typical response exhibited by unexposed infants. Abnormal ERP responses did not consistently correlate with increased inflammatory cytokines within the antibiotic-exposed group. Conclusions: Otherwise healthy infants exposed to antibiotics soon after birth demonstrated altered auditory processing and recognition memory responses, supporting the possibility of a microbiota–gut–brain axis in humans during early life. Impact: Infants exposed to antibiotics after birth demonstrate altered auditory processing and recognition memory responses at 1 month of age.Preclinical models support a role for gut microbiomes in modulating brain function and behavior, particularly in developing brains. This study is one of the first to explore the relevance of these findings for human infants.The findings of this study have implications for the management and follow-up of at-risk infants with exposure to gut-microbiome disrupting factors and lay foundation for future studies to further characterize the short- and long-term effects of gut microbiome perturbation on brain development.
Bibliographical noteFunding Information:
This project was supported by NIH R01HD080444 (to E.W.D.) and NIH R21HD099473 (to C.A.G.).
© 2020, International Pediatric Research Foundation, Inc.