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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
Integrated multi-omics reveals distinct maternal and neonatal gut microbial and metabolic signatures associated with
Xiangyu Bian1, Huisong Xu2, Jianqiang Li1
1State Key Laboratory for Quality and Safety of Agro-products & Food Sciences Institute, Zhejiang Academy of Agricultural Sciences, Hangzhou, China.
Insights
Early life gut microbiome and metabolome differ in infants born small for gestational age (SGA). These alterations in gut bacteria and metabolites in SGA neonates and mothers may impact future metabolic health.
Area of Science:
- Microbiology
- Metabolomics
- Neonatal Health
Background:
- Infants born small for gestational age (SGA) face increased risks for later metabolic disorders.
- The gut microbiota and metabolomic profiles in SGA mother-infant dyads are not well understood.
Purpose of the Study:
- To investigate the fecal metagenomic, metabolomic, and short-chain fatty acid (SCFA) profiles in SGA and appropriate for gestational age (AGA) mother-infant dyads.
- To identify early-life gut microbial and metabolic signatures associated with being born SGA.
Main Methods:
- Integrated analysis of fecal metagenomics, metabolomics, and SCFA profiling in 10 SGA and 10 AGA mother-infant dyads.
- Evaluation of taxonomic composition, microbial function, carbohydrate-active enzyme (CAZyme) profiles, and metabolite pathways.
Main Results:
- SGA neonates showed reduced microbial richness, altered beta-diversity, and increased Enterococcus faecalis and Escherichia coli.
- SGA mothers had divergent CAZyme gene profiles and altered polysaccharide degradation capacity.
- Metabolomic analysis revealed perturbed tryptophan metabolism and disrupted SCFA profiles (increased butyrate in mothers, reduced propionate/isobutyrate in neonates).
Conclusions:
- Distinct early fecal microbiome and metabolome features are present in SGA neonates within 48 hours of birth.
- These findings suggest differences in initial colonization and metabolism in SGA infants.
- Longitudinal follow-up is warranted to understand the long-term implications for metabolic health.
Introduction:
Children born small for gestational age (SGA) have an elevated risk of developing metabolic disorders in later life. However, the underlying gut microbiota and metabolomic alterations in SGA mother-infant dyads remain poorly understood.
Methods:
We performed an integrated analysis of fecal metagenomics, metabolomics, and short-chain fatty acids (SCFAs) profiling in 10 SGA and 10 appropriate for gestational age (AGA) mother-infant dyads at term. Taxonomic composition, microbial functional pathways, carbohydrate-active enzyme (CAZyme) profiles, differential metabolites, and metabolite pathway enrichment were systematically evaluated.
Results And Discussion:
SGA neonates exhibited reduced microbial richness (Chao1 index), distinct beta-diversity, and differential abundance of key bacterial species including increased Enterococcus faecalis and Escherichia coli. Functionally, SGA maternal subjects showed divergent profiles in CAZyme genes, with lower abundance of glycoside hydrolase family 13 subfamily 16, glycosyl transferase family 66, and carbohydrate-binding module family 6, and altered structural polysaccharide degradation capacity. Metabolomic profiling revealed significant perturbations in tryptophan metabolism pathways, notably enriched in kynurenine and taurine derivatives in SGA mother and neonates. Notably, SCFA profiles were disrupted, with increased butyrate in SGA mother and reduced propionate and isobutyrate in SGA neonates. Microbe-metabolite correlation networks revealed strong associations between SGA-specific bacterial taxa and fecal metabolites. In conclusion, our analysis identifies distinct features of the early fecal microbiome and metabolome within 48 h of birth in SGA neonates compared with AGA peers, reflecting differences in initial colonization and metabolism that warrant longitudinal follow-up.

