C-section and systemic inflammation synergize to disrupt the neonatal gut microbiota and brain development in a model of prematurity
Infants born very preterm (below 28 weeks of gestation) are at high risk of developing neurodevelopmental disorders, such as intellectual deficiency, autism spectrum disorders, and attention deficit. Preterm birth often occurs in the context of perinatal systemic inflammation due to chorioamnionitis and postnatal sepsis. In addition, C-section is often performed for very preterm neonates to avoid hypoxia during a vaginal delivery. We have developed and characterized a mouse model based on intraperitoneal injections of IL-1β between postnatal days one and five to reproduce perinatal systemic inflammation. This model replicates several neuropathological, brain imaging, and behavioral deficits observed in preterm infants. We hypothesized that C-sections could synergize with systemic inflammation to induce more severe brain abnormalities. We observed that C-sections significantly exacerbated the deleterious effects of IL-1β on reduced gut microbial diversity, increased levels of circulating peptidoglycans, abnormal microglia/macrophage reactivity, impaired myelination, and reduced functional connectivity in the brain relative to vaginal delivery plus intraperitoneal saline. These data demonstrate the deleterious synergistic effects of C-section and neonatal systemic inflammation on brain maldevelopment and malfunction, two conditions frequently observed in very preterm infants, who are at high risk of developing neurodevelopmental disorders.
Authors
- Juliette Van Steenwinckel (ORCID: https://orcid.org/0000-0003-3463-4856)
- Irvin Sautet
- David Guenoun (ORCID: https://orcid.org/0000-0001-8377-4703)
- Rebeca Martín (ORCID: https://orcid.org/0000-0002-5980-4113)
- Amazigh Mokhtari (ORCID: https://orcid.org/0000-0002-6438-8978)
- Mireille Laforge (ORCID: https://orcid.org/0000-0002-1892-5250)
- Boris Matrot (ORCID: https://orcid.org/0000-0002-7845-9618)
- Pierre Gressèns
- Rochellys Diaz Heijtz (ORCID: https://orcid.org/0000-0001-6821-2569)
- Jean-Claude Mollet
- Bobbi Fleiss (ORCID: https://orcid.org/0000-0001-7828-673X)
- Cécile Morin (ORCID: https://orcid.org/0000-0002-8557-3937)
- Sead Chadi
- Cindy Bokobza (ORCID: https://orcid.org/0000-0003-0992-4317)
- Charlie Demené (ORCID: https://orcid.org/0000-0002-5329-700X)
- Julien Pansiot
- Sandrine Auger
- Andrée Delahaye‐Duriez (ORCID: https://orcid.org/0000-0003-4324-7372)
- Leslie Schwendimann (ORCID: https://orcid.org/0000-0002-3577-1062)
- Valérie Faivre (ORCID: https://orcid.org/0000-0001-6392-2297)
- Sihao Diao (ORCID: https://orcid.org/0000-0002-3644-7694)
- Flora Faure (ORCID: https://orcid.org/0000-0001-9367-8862)
- Jennifer Hua (ORCID: https://orcid.org/0000-0003-2014-918X)
- Ariane Heydari Olya
- Lara Tabet
- Mickaël Tanter (ORCID: https://orcid.org/0000-0001-7739-8051)
Institutions
- Inserm (FR)
- Université Paris Cité (FR)
- AgroParisTech (FR)
- Université Paris-Saclay (FR)
- Karolinska Institutet (SE)
- Microbiologie de l’alimentation au service de la santé (FR)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- NeuroDiderot (FR)
- RMIT University (AU)
Publication Details
- Journal
- Brain Behavior and Immunity
- Published
- 2024-10-21
- DOI
- https://doi.org/10.1016/j.bbi.2024.10.023
- Citations
- 9
- Primary Topic
- Infant Development and Preterm Care
- Type
- article
- Field-Weighted Citation Impact
- 9.98
Funders
- Fondation Air Liquide
- European Commission
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Vetenskapsrådet
- Fondation de France
- Fédération pour la Recherche sur le Cerveau
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
- Cerebral Palsy Alliance
- Fondation Princesse Grace de Monaco