Deciphering dynamic antibiotics-microbiome-metabolome interactions in preterm infants using systems biology

Area of Science:

• Neonatal medicine
• Microbiome research
• Metabolomics

Background:

• Preterm infants often receive antibiotics to prevent infections.
• The effects of these antibiotics on the developing gut microbiome and metabolome are complex and significant.

Purpose of the Study:

• To systematically assess the impact of antibiotic exposure on the gut microbiota and metabolome in preterm infants.
• To identify specific antibiotic effects and their association with clinical outcomes like necrotizing enterocolitis (NEC).

Main Methods:

• Analysis of longitudinal stool samples from 54 extremely- and very-low-birthweight infants.
• Integration of clinical data, 16S rRNA microbiome profiling, targeted metabolomics, and community-scale metabolic modeling.
• In silico metabolic modeling to identify microbial contributions to metabolite production.

Main Results:

• Antibiotic exposure reduced microbial diversity and beneficial taxa, altering short-chain fatty acids (SCFAs) and bile acids.
• Cephalosporins were linked to increased Staphylococcus and potentially reduced bile acid diversity.
• NEC samples showed SCFA depletion and enrichment of antibiotic-resistant bacteria.
• In silico models confirmed microbial SCFA producers and metabolite trends.

Conclusions:

• Antibiotic regimens significantly perturb the neonatal gut ecosystem.
• There is a need for precision antibiotic stewardship to maintain microbiome functions.
• Protecting the gut microbiome can reduce disease risks in preterm infants.