Limosilactobacillus reuteri normalizes blood–brain barrier dysfunction and neurodevelopment deficits associated with prenatal exposure to lipopolysaccharide

ABSTRACT

Maternal 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.

KEYWORDS:

• Maternal inflammation
• lipopolysaccharide
• probiotics
• blood–brain barrier

Acknowledgment(s)

The authors would like to thank Dr. Christine Labno at the Integrated Light Microscopy Core Facility at the University of Chicago for her technical support for imaging analysis and Nicholas Dylla at the Duchossois Family Institute of the University of Chicago for his support in 16S rRNA sequencing analysis. The current work is supported by NIH R01 HD105234 (E. C. Claud), NIH R21 NS121432 (J. Lu), NIDDKP30DK42086 (Center for Interdisciplinary Study of inflammatory Intestinal Disorders (C-IID)), and the SET Center and The Duchossois Family Institute of the University of Chicago.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data are available from the corresponding author on request. https://www.ncbi.nlm.nih.gov/bioproject/PRJNA866398

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2178800

Additional information

Funding

This current work is supported in part by National Institutes of Health R01 HD105234 (E. C. Claud), National Institutes of Health R21 NS121432 (J. Lu), Center for Interdisciplinary Study of Inflammatory Intestinal Disorders (C-IID) National Institutes of Health P30DK042086, The Duchossois Family Institute and The SET Center of the University of Chicago.