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Microbiome Influences Brain’s Immune Cells in a Sex and Age-dependent manner

21 Dec 2017 | By INSERM (Newsroom) | Cell biology, development and evolution


A joint study conducted by Inserm researchers from IBENS (Institute of Biology of the Ecole Normale Supérieure – Inserm/CNRS/ENS) in Paris and researchers from SIgN (Singapore Immunology Network, A*STAR) in Singapore reveals a hitherto undiscovered impact of microbiota on immune brain cells, occurring from fetal stages. These cells, called microglia, which are known players in brain development and functioning, differentially respond to microbiome perturbations in male or female mice. These results are published in Cell.

Microglia are immune cells that respond to traumatic injury or inflammatory signals to protect the brain, acting as sensors of various environmental signals. In addition to their role as immune sentinels, microglia have also been show to regulate several steps of brain wiring and functioning. Consistently, microglia dysfunction has been linked with the etiology of several neurodegenerative diseases and neurodevelopmental disorders, including Schizophrenia or Autism Spectrum Disorders. Microglia therefore play major roles in brain circuits and could constitute an entry point for environmental signals.

To test this hypothesis, Morgane Thion and Sonia Garel, Inserm researchers, together with their associates, used a multidisciplinary approach involving germ-free mice, which lack all the microbiome, and adult mice treated with antibiotics, which acutely destroys the gut flora. Through a combination of global genomic analyses and histological studies, researchers have shown that microglia are profoundly affected by microbiota disruption, already from prenatal stages. Strikingly, the impact of the microbiome on microglia depended on the sexual identity and the age: microglia of males were perturbed prenatally whereas those of females were affected in adulthood. This surprising sexual dimorphism echoes the fact that many neurodevelopmental disorders have a higher incidence in men, whereas autoimmune diseases are more prevalent in women.

While the underlying mechanisms and consequences remain to be discovered, this study reveals a key role of microglia at the brain/environment interface and shows that males and females have distinct susceptibilities time windows to microbiome alterations. For the authors, these elements should be systematically taken into consideration at preclinical and clinical level.

Researcher Contact
Sonia Garel Directrice de recherche Inserm Institut de biologie de l’Ecole normale supérieure (IBENS), Ecole Normale Supérieure, Paris Tel : 06 33 49 48 14 Mel : rf.sne.eigoloib@lerag
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Microbiome influences prenatal and adult microglia in a sex-specific manner   Morgane Sonia Thion1,15, Donovan Low2,15, Aymeric Silvin2,16, Jinmiao Chen2,16, Pauline Grisel1,16, Jonas Schulte-Schrepping3, Ronnie Blecher4, Thomas Ulas3, Paola Squarzoni1, Guillaume Hoeffel2, Fanny Coulpier1, Eleni Siopi5, Friederike Sophie David3,Claus Scholz3, Foo Shihui2, Josephine Lum2, Arlaine Anne Amoyo6, Anis Larbi2, Michael Poidinger2, Anne Buttgereit7, Pierre-Marie Lledo5, Melanie Greter7, Jerry Kok Yen Chan8,9, Ido Amit4, Marc Beyer3,10, Joachim Ludwig Schultze3,11, Andreas Schlitzer2,12,Sven Pettersson11,14, Florent Ginhoux2,17,18,*, Sonia Garel1,17,*   1Institut de Biologie de l’Ecole normale supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Research University, 75005 Paris, France 2Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, 138648, Singapore 3Genomics and Immunoregulation, Life and Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany 4Department of Immunology, Weizmann Institute of Science, 76100 Rehovot, Israel 5Institut Pasteur, Unité Perception et Mémoire, CNRS, UMR 3571, F-75015 Paris, France 6National Cancer Centre, Singapore, 169610, Singapore 7Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland 8Department of Reproductive Medicine, KK Women's and Children's Hospital, Singapore, 229899, Singapore 9KK Research Centre, KK Women’s and Children’s Hospital, 100 Bukit Timah Road, Singapore, 229899, Singapore 10Molecular Immunology in Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany 11Platform of Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases and the University of Bonn, 53175 Bonn, Germany 12Myeloid Cell Biology, LIMES-Institute, University of Bonn, 53115 Bonn, Germany 13Lee Kong Chian School of Medicine and School of Biological Sciences, Nanyang Technological University, Singapore, 639798, Singapore 14Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, 17165, Sweden Cell,