Limosilactobacillus reuteri normalizes blood–brain barrier dysfunction and neurodevelopment deficits associated with prenatal exposure to lipopolysaccharide
Jing Lu,
Xiaobing Fan,
Lei Lu,
Yueyue Yu,
Erica Markiewicz,
Jessica C. Little,
Ashley M. Sidebottom,
Erika C. Claud
Affiliations
Jing Lu
Department of Pediatrics, The University of Chicago, Pritzker School of Medicine, Chicago, IL, USA
Xiaobing Fan
Magnetic Resonance Imaging and Spectroscopy Laboratory, The University of Chicago, Department of Radiology, Chicago, IL, USA
Lei Lu
Department of Pediatrics, The University of Chicago, Pritzker School of Medicine, Chicago, IL, USA
Yueyue Yu
Department of Pediatrics, The University of Chicago, Pritzker School of Medicine, Chicago, IL, USA
Erica Markiewicz
Magnetic Resonance Imaging and Spectroscopy Laboratory, The University of Chicago, Department of Radiology, Chicago, IL, USA
Jessica C. Little
Duchossois Family Institute, The University of Chicago, Host-Microbe Metabolomics Facility, Chicago, IL, USA
Ashley M. Sidebottom
Duchossois Family Institute, The University of Chicago, Host-Microbe Metabolomics Facility, Chicago, IL, USA
Erika C. Claud
Department of Pediatrics, The University of Chicago, Pritzker School of Medicine, Chicago, IL, USA
ABSTRACTMaternal immune activation (MIA) derived from late gestational infection such as seen in chorioamnionitis poses a significantly increased risk for neurodevelopmental deficits in the offspring. Manipulating early microbiota through maternal probiotic supplementation has been shown to be an effective means to improve outcomes; however, the mechanisms remain unclear. In this study, we demonstrated that MIA modeled by exposing pregnant dams to lipopolysaccharide (LPS) induced an underdevelopment of the blood vessels, an increase in permeability and astrogliosis of the blood–brain barrier (BBB) at prewean age. The BBB developmental and functional deficits early in life impaired spatial learning later in life. Maternal Limosilactobacillus reuteri (L. reuteri) supplementation starting at birth rescued the BBB underdevelopment and dysfunction-associated cognitive function. Maternal L. reuteri-mediated alterations in β-diversity of the microbial community and metabolic responses in the offspring provide mechanisms and potential targets for promoting BBB integrity and long-term neurodevelopmental outcomes.
