Postnatal 14D is the Key Window for Mice Intestinal Development- An Insight from Age-Dependent Antibiotic-Mediated...

Area of Science:

• Microbiology
• Immunology
• Developmental Biology

Background:

• The postnatal period is crucial for gastrointestinal tract and immune system development.
• Gut microbiota plays a vital role in host health, immunity, and development, but its early-life functions require further elucidation.
• Understanding gut microbiota's impact on intestinal integrity and immune profile during early development is essential.

Purpose of the Study:

• To investigate the effects of antibiotic-mediated gut microbiota perturbation on intestinal integrity, epithelial development, and immune profile in neonatal mice.
• To identify critical developmental periods and specific microbial compositions influencing neonatal intestinal health.

Main Methods:

• Antibiotic-induced gut microbiota perturbation in mice at postnatal days 7, 14, 21, and 28.
• 16S rRNA metagenomic analysis to assess microbial composition.
• Analysis of barrier integrity, tight junction proteins (TJPs), intestinal epithelial cell (IEC) markers, and inflammatory cytokines.
• Microbiota transplantation to confirm causal roles.

Main Results:

• Antibiotic treatment led to age-related changes in gut microbiota, increasing Proteobacteria and decreasing Bacteroidetes and Firmicutes.
• Significant disruption of intestinal barrier integrity, reduced TJPs and IEC markers, and increased systemic inflammation were observed at postnatal day 14.
• Microbiota transplantation demonstrated a causal role of specific bacteria in restoring barrier function.

Conclusions:

• Postnatal day 14 represents a critical window for neonatal intestinal development, significantly influenced by gut microbiota composition.
• Early-life gut microbiota perturbation can lead to detrimental effects on intestinal integrity and immune homeostasis.
• Specific microbial compositions are crucial for maintaining neonatal intestinal barrier functions.