Project Summary
The gut microbiota, a community of symbiotic bacteria, fungi, and archaea residing in the mammalian
gastrointestinal tract, plays an integral role in the neurodevelopment and neurophysiology of the host. Its
disruption has been associated with neurodevelopmental and neurodegenerative diseases. Microglia are the
resident immune cells in the central nervous system; they are continually influenced by gut microbiota, raising
the possibility that microglia dysfunction may be the link between dysbiosis and altered brain functions. This
proposal investigates how early-life exposure to penicillin, the most-used antibiotics in perinatal medicine,
affects the interplay between gut microbiota, the immune system, cortical development, and sensory
processing in mice, and explores the potential of probiotics as a preventative measure. Aim 1 studies how
perinatal penicillin exposure (PPE)-induced gut dysbiosis affects cortical microglia and sensory processing in
adolescent and adult mice. It also explores whether early postnatal normalization of gut microbiota prevents
microglia activation and behavioral defects later in life. Aim 2 studies how PPE alters microglia motility, their
synaptic contact, synapse pruning, and cortical neuronal activities associated with the defective sensory
processing. This study will advance our understanding of the gut-immune-brain axis in neural development,
circuit function, and behavior, with significant relevance to clinical medicine and public health.
