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Updated: Oct 17, 2025
A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
Maternal gut microbiome regulates immunity to RSV infection in offspring
Wendy Fonseca1, Carrie-Anne Malinczak1, Kei Fujimura2
1Department of Pathology, University of Michigan, Ann Arbor, MI.
Insights
Maternal Lactobacillus supplementation protects offspring from respiratory syncytial virus (RSV) by altering the gut microbiome and reducing inflammation. This probiotic approach enhances neonatal airway immunity against RSV infection.
Area of Science:
- Immunology
- Microbiology
- Neonatal Health
Background:
- Early life respiratory syncytial virus (RSV) infection can cause lasting immune changes.
- Previous studies showed Lactobacillus johnsonii reduced airway inflammation in adult mice post-RSV.
Purpose of the Study:
- To investigate if maternal Lactobacillus johnsonii supplementation protects offspring from RSV-induced airway immunopathology.
- To determine the mechanisms behind this protection, including microbiome and metabolic changes.
Main Methods:
- Mice were supplemented with Lactobacillus johnsonii during pregnancy and lactation.
- Offspring were infected with RSV, and immune responses, lung pathology, and microbiome composition were analyzed.
- Cross-fostering experiments were used to distinguish prenatal and postnatal effects.
Main Results:
- Offspring of supplemented mothers showed reduced airway mucus and Th2 immune responses to RSV.
- Maternal and offspring gut microbiomes were more consistent with supplementation.
- Plasma and breastmilk from supplemented mothers, and offspring plasma, had lower inflammatory metabolites.
- Prenatal Lactobacillus exposure decreased Th2 cytokines and lung inflammation; postnatal exposure reduced mucus production.
Conclusions:
- Lactobacillus modulation of the maternal microbiome and metabolic reprogramming provides significant airway protection against RSV in neonates.
- This highlights a potential probiotic strategy for preventing severe RSV outcomes in infants.
Abstract:
Development of the immune system can be influenced by diverse extrinsic and intrinsic factors that influence the risk of disease. Severe early life respiratory syncytial virus (RSV) infection is associated with persistent immune alterations. Previously, our group had shown that adult mice orally supplemented with Lactobacillus johnsonii exhibited decreased airway immunopathology following RSV infection. Here, we demonstrate that offspring of mice supplemented with L. johnsonii exhibit reduced airway mucus and Th2 cell-mediated response to RSV infection. Maternal supplementation resulted in a consistent gut microbiome in mothers and their offspring. Importantly, supplemented maternal plasma and breastmilk, and offspring plasma, exhibited decreased inflammatory metabolites. Cross-fostering studies showed that prenatal Lactobacillus exposure led to decreased Th2 cytokines and lung inflammation following RSV infection, while postnatal Lactobacillus exposure diminished goblet cell hypertrophy and mucus production in the lung in response to airway infection. These studies demonstrate that Lactobacillus modulation of the maternal microbiome and associated metabolic reprogramming enhance airway protection against RSV in neonates.
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