Protective effect and mechanism of <i>Lacticaseibacillus paracasei</i> 207-27 administration on colitis in antibiotic-exposed mice in early life

Evidence shows that antibiotic exposure in early life increases the risk of inflammatory bowel disease by causing gut microbiota dysbiosis and affecting intestinal immune system development. This study aimed to investigate the possible protective effect and mechanism of short-term and long-term applications of <i>Lacticaseibacillus paracasei</i> 207-27 for ameliorating gut microbiota disorders due to early-life antibiotic exposure in mice with dextran sulfate sodium (DSS)-induced colitis. We intervened neonatal mice with ceftriaxone, and <i>L. paracasei</i> 207-27 was administered 2 h following antibiotic administration. <i>L. paracasei</i> 207-27 was used for continuous gavage for 3 and 6 weeks. The first batch of mice was sacrificed on day 21, and the second batch was sacrificed on day 46 following a 4-day intervention with 3% DSS to induce colitis. Results showed that on day 21, the ceftri + 207-27 group had higher alpha diversity of the gut microbiota, short-chain fatty acid levels, and splenic immune factor levels than the ceftri group, with significantly lower serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels. On day 46, the 207-27 short-term group had similarly lower splenic and serum IL-6 and TNF-α levels than the DSS group. Regarding colonic IL-17, TNF-α, and interferon-γ (INF-γ) levels, a decreasing trend was observed in the 207-27 short-term and long-term groups compared with that in the ceftri-DSS group, and the 207-27 long-term group had significantly higher claudin and secretory immunoglobulin A levels. In conclusion, short-term <i>L. paracasei</i> 207-27 administration improves gut microbiota composition and effectively alleviates colitis symptoms, and long-term <i>L. paracasei</i> 207-27 administration protects the intestinal barrier.IMPORTANCEThis study is the first to apply <i>Lacticaseibacillus paracasei</i> 207-27 on colitis in antibiotic-exposed mice in early life and observe the protective effect. Short-term <i>L. paracasei</i> 207-27 administration improves the symptoms of colitis, whereas long-term <i>L. paracasei</i> 207-27 administration promotes intestinal barrier function.