Authors
Kenneth Klingenberg Barfod, Julian Chun Lui, Signe Schmidt Kjølner Hansen, Sreyoshee Sengupta, Line Sidsel Fisker Zachariassen, Axel Kornerup Hansen, Jorid Birkelund Sørli
Publication date
2023/3/6
Journal
Frontiers in Microbiomes
Volume
2
Pages
1085508
Publisher
Frontiers Media SA
Description
Early-life changes to lung and gut microbiota have been linked to alterations in immune responses that may lead to pulmonary diseases later in life. Associations between early-life microbiota, germ-free status, lung gene expression, lung development and function are not well described. In this study, we compare early-life lung gene transcription under germ-free and different perinatal microbial exposures, and analyze with a predetermined focus on lung capacity and lung surfactant. We also analyze the later-in-life physiological measures of breathing patterns and lung surfactant function between the germ-free, gnotophoric and gnotobiotic offspring. To achieve this, we kept pregnant BALB/c germ-free mice in separate germ-free isolators until exposure to either A: no exposure (GF), B: Bifidobacterium animalis ssp. Lactis (BI04) or C: full cecum content harvested from other female SPF mice (Cecum). Subsequently, perinatally exposed offspring were used for the analyses. Lung tissue transcriptomics analysis was done at postnatal day 10 (PNday10) at the first phase of lung alveolar development. Head-out plethysmography for breathing pattern analysis was performed on the siblings at PNday23 followed by lung surfactant collection. The function of the collected lung surfactant was then analyzed ex vivo using the constrained drop surfactometer. Our results show that lung transcriptomics had differentially expressed genes related to surfactant turnover between groups and sex at PNday10. They also show that the GF and BI04 animals had lower respiratory rate than Cecum mice, or compared to age-matched specific pathogen-free (SPF) reference …