Infants exposed to antibiotics after birth have altered recognition memory responses at one month of age.

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. Fig. 1SCHEMATIC OF THE 64-CHANNEL HYDROCEL GEODESIC SENSOR NET (NETSTATION, EGI) AND CLUSTERS OF ELECTRODES (CIRCLED) USED FOR DATA ANALYSIS OF P2 WAVEFORMS.: Leads 7, 9, and 12 make up the right frontal group; leads 16, 20, and 22 comprise the right central lead grouping; leads 3, 54, and 60 the left frontal, and 49, 50, and 51 the left central lead grouping.Fig. 2GRANDMEAN EVENT-RELATED POTENTIALS IN RESPONSE TO MOTHER'S VOICE (BLACK LINE) AND STRANGER'S VOICE (GRAY LINE).: Each row contains a representative lead from each scalp electrode region cluster. Arrowheads denote P2. Equivalent of 10-10 scalp net system lead is indicated in the box to the right of each grandmean x-axis.Fig. 3HEAT MAPS OF P2 AMPLITUDE RESPONSES (ELECTRICAL POTENTIALS DEPICTED AS A COLOR GRADIENT) TO MOTHER AND STRANGER VOICE IN INFANTS EXPOSED TO ANTIBIOTICS OR NOT.: Cranium orientation indicated by letters (A: anterior, P: posterior, L: left, R: right). Black dots represent individual scalp electrode locations.Fig. 4DIFFERENCE IN P2 AMPLITUDE (FAMILIAR-NOVEL) BY SCALP REGION.: Dark gray, control group; light gray, antibiotic-treated group. *p < 0.05.