Abstract
The microbiota plays important roles in host metabolism and immunity, and its disruption affects adult brain physiology and behavior. Although such findings have been attributed to altered neurodevelopment, few studies have actually examined microbiota effects on the developing brain. This review focuses on developmental effects of the earliest exposure to microbes. At birth, the mammalian fetus enters a world teeming with microbes which colonize all body sites in contact with the environment. Bacteria reach the gut within a few hours of birth and cause a measurable response in the intestinal epithelium. In adults, the gut microbiota signals to the brain via the vagus nerve, bacterial metabolites, hormones, and immune signaling, and work in perinatal rodents is beginning to elucidate which of these signaling pathways herald the very first encounter with gut microbes in the neonate. Neural effects of the microbiota during the first few days of life include changes in neuronal cell death, microglia, and brain cytokine levels. In addition to these effects of direct exposure of the newborn to microbes, accumulating evidence points to a role for the maternal microbiota in affecting brain development via bacterial molecules and metabolites while the offspring is still in utero. Hence, perturbations to microbial exposure perinatally, such as through C-section delivery or antibiotic treatment, alter microbiota colonization and may have long-term neural consequences. The perinatal period is critical for brain development and a close look at microbiota effects during this time promises to reveal the earliest, most primary effects of the microbiota on neurodevelopment.
Highlights
The womb has long been assumed to be sterile, with the first direct exposure to microbes occurring at birth
We focus on microbe exposure in the immediate peri-partum period to address key questions and identify gaps in our knowledge related to: (1) how microbes signal to the neonatal brain, (2) which microbes first colonize the gut and exactly when that occurs, (3) what the effects are of microbe exposure on the neonatal brain, and (4) whether effects of microbe exposure on brain development begin in utero
The gut microbiota is comprised of bacteria, viruses, fungi, and protozoa, bacteria have received by far the most attention to date
Summary
The womb has long been assumed to be sterile, with the first direct exposure to microbes occurring at birth. Other studies do not see offspring-associated microbiota in healthy pregnancies distinct from contaminating DNA, supporting the “sterile womb” hypothesis (e.g., de Goffau et al, 2019; reviewed in Walter and Hornef, 2021) Regardless of this debate’s outcome, all agree that microbes from maternal and environmental sources rapidly and densely colonize the neonate at birth. Germ-free (GF) mice, for example, have alterations in social behavior, stress responding, cognition, and other functions (Cryan and Dinan, 2012) Some of these effects can be corrected with exposure to a microbiota in adolescence, but others persist (e.g., Clarke et al, 2013), suggesting that early life is a sensitive period for effects of microbe exposure on the brain.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
