Brain effects of gestating germ-free persist in mouse neonates despite acquisition of a microbiota at birth

Frontiers in Neuroscience

Neuroscience

Benoit Chassaing¹  Charlène J. G. Dauriat¹  Nicole M. Ronczkowski²  Aviva Gars³  Hannah Sturgeon³  Dhanya N. Pyaram³  Alexandra Castillo-Ruiz³  Nancy G. Forger³ 

[1] INSERM U1016, Team “Mucosal Microbiota in Chronic Inflammatory Diseases,” Université Paris Cité, Paris, France;Medical College of Georgia, Augusta University, Augusta, GA, United States;Neuroscience Institute, Georgia State University, Atlanta, GA, United States;

关键词: cross-fostering;    cell death;    microglia;    forebrain size;    bacterial load;    colonic content;   

DOI  :  10.3389/fnins.2023.1130347

 received in 2022-12-23, accepted in 2023-04-10,  发布年份 2023

来源: Frontiers

【 摘 要 】

At birth, mammals experience a massive colonization by microorganisms. We previously reported that newborn mice gestated and born germ-free (GF) have increased microglial labeling and alterations in developmental neuronal cell death in the hippocampus and hypothalamus, as well as greater forebrain volume and body weight when compared to conventionally colonized (CC) mice. To test whether these effects are solely due to differences in postnatal microbial exposure, or instead may be programmed in utero, we cross-fostered GF newborns immediately after birth to CC dams (GF→CC) and compared them to offspring fostered within the same microbiota status (CC→CC, GF→GF). Because key developmental events (including microglial colonization and neuronal cell death) shape the brain during the first postnatal week, we collected brains on postnatal day (P) 7. To track gut bacterial colonization, colonic content was also collected and subjected to 16S rRNA qPCR and Illumina sequencing. In the brains of GF→GF mice, we replicated most of the effects seen previously in GF mice. Interestingly, the GF brain phenotype persisted in GF→CC offspring for almost all measures. In contrast, total bacterial load did not differ between the CC→CC and GF→CC groups on P7, and bacterial community composition was also very similar, with a few exceptions. Thus, GF→CC offspring had altered brain development during at least the first 7 days after birth despite a largely normal microbiota. This suggests that prenatal influences of gestating in an altered microbial environment programs neonatal brain development.

【 授权许可】

Unknown   
Copyright © 2023 Castillo-Ruiz, Gars, Sturgeon, Ronczkowski, Pyaram, Dauriat, Chassaing and Forger.