Pediococcus acidilactici A1-2 as a Promising Antiviral Probiotic Candidate

Although probiotics are best known for supporting intestinal health, some strains show antiviral potential. We characterized Pediococcus acidilactici A1-2, a novel strain from fermented apple, and evaluated its ac-tivity against influenza A (H1N1) in porcine intestinal epithelial cells. A1-2 cell-free supernatant (CFS) re-duced H1N1 haemagglutinin activity 16-fold, retaining 8-fold inhibition at neutral pH, indicating pH-stable secreted compounds rather than acidification alone. Preincubating virus with 20% CFS reduced infectious titer >5 log10 (100,000-fold; p<0.0001). CFS and live cells each independently reduced infectious titer (p≤0.01) and suppressed IL-6 without attenuating virus-induced barrier gene upregulation or causing apopto-sis. Untargeted metabolomics identified 313 enriched compounds, several previously linked to antiviral ac-tivity. Whole-genome sequencing confirmed identity (ANI 0.992) and probiotic genes (bile salt hydrolase, adhesion, acid-stress resistance, vitamin biosynthesis) with no antimicrobial resistance genes. A1-2 also re-covered metabolically under simulated gastrointestinal stress, identifying it as a promising antiviral probiotic candidate.