Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner


Morgane Sonia Thion, Donovan Low, Aymeric Silvin, Jinmiao Chen, Pauline Grisel, Jonas Schulte-Schrepping, Ronnie Blecher, Thomas Ulas, Paola Squarzoni, Guillaume Hoeffel, Fanny Coulpier, Eleni Siopi, Friederike Sophie David, Claus Scholz, Foo Shihui, Josephine Lum, Arlaine Anne Amoyo, Anis Larbi, Michael Poidinger, Anne Buttgereit, Pierre-Marie Lledo, Melanie Greter, Jerry Kok Yen Chan, Ido Amit, Marc Beyer, Joachim Ludwig Schultze, Andreas Schlitzer, Sven Pettersson, Florent Ginhoux, Sonia Garel


Microglia are embryonically seeded macrophages that contribute to brain development, homeostasis, and pathologies. It is thus essential to decipher how microglial properties are temporally regulated by intrinsic and extrinsic factors, such as sexual identity and the microbiome. Here, we found that microglia undergo differentiation phases, discernable by transcriptomic signatures and chromatin accessibility landscapes, which can diverge in adult males and females. Remarkably, the absence of microbiome in germ-free mice had a time and sexually dimorphic impact both prenatally and postnatally: microglia were more profoundly perturbed in male embryos and female adults. Antibiotic treatment of adult mice triggered sexually biased microglial responses revealing both acute and long-term effects of microbiota depletion. Finally, human fetal microglia exhibited significant overlap with the murine transcriptomic signature. Our study shows that microglia respond to environmental challenges in a sex- and time-dependent manner from prenatal stages, with major implications for our understanding of microglial contributions to health and disease.

Dataset information:

Genomic assay Microarray Samples Microglia and its progenitors
Method for deriving gene sets Hierarchical clustering Number of gene sets 7
Figure source Figure 1 Data source Table S1

Associated gene sets:

Gene set # Description No. of genes
1 Progenitor 1 1033
2 Progenitor 2 1583
3 Progenitor 3 1399
4 Embryonic 1 1017
5 Embryonic 2 1611
6 Adult 1 1826
7 Adult 2 890

A total of 9359 genes are associated with this dataset.