Caesarean Delivery's Effect on the Early Life Microbiome and Neurodevelopment

项目摘要/摘要

PROJECT SUMMARY / ABSTRACT The microbiome is the community of bacteria, fungi, and viruses that live in and on a host. Over the past few decades, advances in sequencing technology have allowed us to better understand the composition of the mammalian microbiome and the ways it affects host development. Recent evidence shows that Caesarean- section delivery, though a medical necessity for some births, may disrupt the vertical transfer of microbiota from mother to child. This can cause different microbial communities during critical periods of development. The brain may be particularly sensitive to microbiome changes because neurogenesis in many brain regions and myelination continue through childhood. This may be one explanation for the increased prevalence of neurodevelopmental disorders like autism spectrum disorder and attention deficit hyperactivity disorder that are associated with Caesarean delivery. Nevertheless, it remains unknown whether microbial communities, and specifically those caused by differential birth mode, can cause neuroanatomical changes. To advance our understanding of Caesarean delivery’s effect on neurodevelopment, we will use a mouse model of Caesarean delivery that will allow us to separately quantify the effect of birth mode on both the offsprings’ microbial communities (Aim 1) and neurodevelopment (Aim 2). We hypothesize that perturbation of the infant microbiome by Caesarean delivery will disrupt the normal pattern of neurodevelopment in pre-weaning mice (≤ postnatal day 21). To test this hypothesis, in Aim 1 we will study microbial communities through next generation sequencing, community structure analysis, and predicted bacterial gene content . Additionally, the direct and local effects of the microbial community will be quantified by mRNA transcriptomic analysis of gastrointestinal tissues. In Aim 2, we will study brain development through histology and transcriptomics of the cerebellum and hippocampus. Both regions exhibit neurodevelopment in the early postnatal period and are implicated in the pathogenesis of neurodevelopmental diseases. Gene expression will be quantified in each brain region through mRNA transcriptomics. The results of this proposed study may inform targeted microbiome-based interventions that restore microbial composition and function and facilitate proper neurogenesis. This research will be completed between two labs at Rutgers university that have expertise in microbiome analysis and neurodevelopment. The fellow will receive training to achieve his goal of becoming an independent physician-scientist. This will entail field-specific training in microbial ecology and neuroscience, as well as the generalizable skills necessary to become an independent investigator, including: experimental design, scientific writing and communication, and presentation skills.