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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
Persistence of birth mode-dependent effects on gut microbiome composition, immune system stimulation and
Susheel Bhanu Busi1, Laura de Nies1, Janine Habier1
1Systems Ecology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
Insights
Caesarean section delivery (CSD) alters infant gut microbiome composition and immune priming long-term. These birth mode differences persist to 1 year, impacting microbial populations and antimicrobial resistance (AMR) gene abundance.
Area of Science:
- Microbiology
- Immunology
- Genetics
Background:
- Caesarean section delivery (CSD) disrupts the initial seeding of the infant gut microbiome and immune system development compared to vaginal delivery (VD).
- The long-term consequences of these early-life disruptions on microbiome composition and host physiology are not fully understood.
- Investigating these persistent effects is crucial for understanding infant health trajectories.
Purpose of the Study:
- To investigate whether differences in gut microbiome composition and host physiological impacts, established at birth, persist until 1 year of age in infants born via CSD versus VD.
- To characterize the specific microbial populations and functional gene repertoires that differ between CSD and VD infants at 1 year.
- To assess the impact of these microbiome differences on host immune cell responses and antimicrobial resistance (AMR) gene prevalence.
Main Methods:
- High-resolution, quantitative metagenomic analysis of gut microbiomes from infants (CSD and VD) from birth to 1 year.
- Isolation of lipopolysaccharide (LPS) from neonatal stool samples for immune cell stimulation assays.
- Analysis of functional gene repertoires, including antibiotic biosynthesis and AMR genes, within the metagenomes.
Main Results:
- Distinct microbial populations were enriched in CSD infants (e.g., Bacteroides caccae, Bifidobacterium bifidum) versus VD infants (e.g., Faecalibacterium prausnitizii, Bifidobacterium breve) at 1 year.
- LPS from CSD infant stool induced higher levels of tumor necrosis factor alpha (TNF-α) in immune cells compared to VD infant stool.
- Increased abundance of AMR genes, particularly against synthetic antibiotics, was observed in CSD infants early post-birth, with mobile genetic elements contributing to AMR gene spread.
Conclusions:
- Birth mode-dependent differences in early gut microbiome colonization have persistent effects on microbiome composition and host immune priming up to 1 year of age.
- CSD is associated with altered immune responses and a distinct gut microbial profile at 1 year.
- The study highlights the long-lasting impact of CSD on the infant gut microbiome and the potential implications for health and disease, including the development of antimicrobial resistance.
Abstract:
Caesarean section delivery (CSD) disrupts mother-to-neonate transmission of specific microbial strains and functional repertoires as well as linked immune system priming. Here we investigate whether differences in microbiome composition and impacts on host physiology persist at 1 year of age. We perform high-resolution, quantitative metagenomic analyses of the gut microbiomes of infants born by vaginal delivery (VD) or by CSD, from immediately after birth through to 1 year of life. Several microbial populations show distinct enrichments in CSD-born infants at 1 year of age including strains of Bacteroides caccae, Bifidobacterium bifidum and Ruminococcus gnavus, whereas others are present at higher levels in the VD group including Faecalibacterium prausnitizii, Bifidobacterium breve and Bifidobacterium kashiwanohense. The stimulation of healthy donor-derived primary human immune cells with LPS isolated from neonatal stool samples results in higher levels of tumour necrosis factor alpha (TNF-α) in the case of CSD extracts over time, compared to extracts from VD infants for which no such changes were observed during the first year of life. Functional analyses of the VD metagenomes at 1 year of age demonstrate a significant increase in the biosynthesis of the natural antibiotics, carbapenem and phenazine. Concurrently, we find antimicrobial resistance (AMR) genes against several classes of antibiotics in both VD and CSD. The abundance of AMR genes against synthetic (including semi-synthetic) agents such as phenicol, pleuromutilin and diaminopyrimidine are increased in CSD children at day 5 after birth. In addition, we find that mobile genetic elements, including phages, encode AMR genes such as glycopeptide, diaminopyrimidine and multidrug resistance genes. Our results demonstrate persistent effects at 1 year of life resulting from birth mode-dependent differences in earliest gut microbiome colonisation.
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