Antibiotics modulate intestinal immunity and prevent necrotizing enterocolitis in preterm neonatal piglets

Area of Science:

• Neonatal research
• Gastroenterology
• Microbiology

Background:

• Preterm birth, bacterial colonization, and formula feeding are risk factors for necrotizing enterocolitis (NEC).
• The impact of prophylactic antibiotics on intestinal immunity and NEC resistance in neonates remains unclear.

Purpose of the Study:

• To investigate the hypothesis that broad-spectrum antibiotic treatment enhances NEC resistance and improves intestinal structure, function, and immunity in neonates.
• To evaluate the effects of neonatal prophylactic antibiotics on gut health and NEC development in preterm pigs.

Main Methods:

• Preterm pigs delivered via C-section were administered either broad-spectrum antibiotics (gentamycin, ampicillin, metronidazole) or saline for 5 days.
• Evaluated NEC lesions, intestinal structure (villi height, goblet cells), digestive enzyme activity, microbial density, and immune markers.
• Utilized microarray transcriptomics to analyze gene expression related to inflammation, immunity, and metabolism.

Main Results:

• Antibiotic treatment completely prevented NEC lesions (0/11) compared to the control group (85% incidence, P < 0.05).
• Antibiotic-treated pigs showed enhanced intestinal villi, digestive enzyme activity, and goblet cell density, with reduced inflammation markers and gut microbial load.
• Gene expression analysis revealed downregulation of inflammatory genes and upregulation of genes involved in amino acid metabolism, glucose transport, and cell cycle.

Conclusions:

• Neonatal prophylactic antibiotics effectively reduce gut bacterial load and prevent NEC, intestinal atrophy, and inflammation in preterm pigs.
• Antibiotic administration enhances gut metabolism and immunity gene expression, contributing to NEC resistance.
• This study demonstrates the protective role of early-life antibiotics against NEC and associated intestinal pathologies.