Effects of early-life penicillin exposure on the gut microbiome and frontal cortex and amygdala gene expression
Angelina Volkova,
Kelly Ruggles,
Anjelique Schulfer,
Zhan Gao,
Stephen D. Ginsberg,
Martin J. Blaser
Affiliations
Angelina Volkova
Institute for Systems Genetics, New York University Grossman School of Medicine, New York, NY 10016, USA
Kelly Ruggles
Institute for Systems Genetics, New York University Grossman School of Medicine, New York, NY 10016, USA; Department of Medicine, New York University Grossman School of Medicine, New York, NY 10016, USA
Anjelique Schulfer
Department of Medicine, New York University Grossman School of Medicine, New York, NY 10016, USA
Zhan Gao
Department of Medicine, New York University Grossman School of Medicine, New York, NY 10016, USA; Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, NJ 08854, USA
Stephen D. Ginsberg
Center for Dementia Research. Nathan Kline Institute, Orangeburg, NY 10962, USA; Departments of Psychiatry, Neuroscience & Physiology, and NYU Neuroscience Institute, New York University Grossman School of Medicine, New York, NY 10016, USA; Corresponding author
Martin J. Blaser
Department of Medicine, New York University Grossman School of Medicine, New York, NY 10016, USA; Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, NJ 08854, USA; Corresponding author
Summary: We have established experimental systems to assess the effects of early-life exposures to antibiotics on the intestinal microbiota and gene expression in the brain. This model system is highly relevant to human exposure and may be developed into a preclinical model of neurodevelopmental disorders in which the gut–brain axis is perturbed, leading to organizational effects that permanently alter the structure and function of the brain. Exposing newborn mice to low-dose penicillin led to substantial changes in intestinal microbiota population structure and composition. Transcriptomic alterations implicate pathways perturbed in neurodevelopmental and neuropsychiatric disorders. There also were substantial effects on frontal cortex and amygdala gene expression by bioinformatic interrogation, affecting multiple pathways underlying neurodevelopment. Informatic analyses established linkages between specific intestinal microbial populations and the early-life expression of particular affected genes. These studies provide translational models to explore intestinal microbiome roles in the normal and abnormal maturation of the vulnerable central nervous system.
