Postbiotics derived from Lactobacillus acidophilus exhibit prevention and treatment efficacy against rotavirus-induced diarrhea in neonatal mice.

Rotavirus (RV) is the leading cause of severe diarrhea in children under 5 years of age worldwide, and no specific clinical treatments are currently available. Developing a therapeutic agent that combines antiviral properties with the ability to repair the intestinal mucosa holds significant clinical value. In this study, a dual prevention and treatment intervention model was established using neonatal BALB/c mice to systematically investigate the protective effects and underlying mechanisms of Lacidophilin (LA) against RV-induced infectious diarrhea. The results showed that LA significantly alleviated diarrhea symptoms and reduced the loose stool rate and index in infected mice, with superior effects observed in the high-dose and preventive intervention groups. LA repaired RV-induced small intestinal pathological damage, reduced intestinal epithelial apoptosis, restored the expression of tight-junction proteins and mucosal protective factors, and decreased intestinal permeability. It not only inhibited RV replication in vitro and in vivo but also inhibited adenovirus and astrovirus replication in vitro. In addition, LA upregulated sIgA levels in serum and intestinal tissues, reshaped the imbalanced cytokine network, and restored protective Th1-type immunity. Multi-omics analyses revealed that LA regulated the intestinal microbial structure, reversed metabolic disorders, remodeled transcriptomic characteristics, and significantly enriched the PI3K-AKT, PPARγ and NF-κB signaling pathways in RV-infected mice. Molecular verification confirmed that LA repaired the intestinal epithelium by activating the pro-survival PI3K-AKT pathway, restoring normal PPARγ function and inhibiting NF-κB-mediated excessive inflammation. In conclusion, LA exerts a protective effect against RV-induced infectious diarrhea through multi-target synergistic actions of antiviral activity, intestinal barrier repair, immune response regulation, remodeling of the microbiota-metabolism-transcriptome network, and modulation of the PI3K-AKT/PPARγ/NF-κB signaling pathway, providing solid experimental evidence and theoretical support for its clinical translation and application.