Recombinant Lactococcus lactis Expressing IFN-γ Alleviates Viral Enteritis via Microbial and Metabolic Modulation

Abstract Viral enteritis severely impacts the animal industry. Current vaccines and antibiotics have limited efficacy due to virus mutation, drug resistance, and side effects. This study developed an edible lactic acid bacteria (LAB) delivery system, constructing a recombinant strain (pNZ8149-IFN-γ/NZ3900) expressing interferon-γ (IFN-γ) via the nisin-inducible (NICE) system for active IFN-γ release, aiming to provide a novel therapeutic with both probiotic and antiviral functions. Using a mouse viral enteritis model and intestinal organoid coculture, the strain was shown to significantly alleviate intestinal inflammation and tissue damage and reduce serum inflammatory factors. An acute virulence test confirmed its safety. Furthermore, at the organoid level, the recombinant LAB resisted Poly(I:C)-induced inflammation and damage. The innovation lies in the first combination of IFN-γ with food-grade LAB for oral delivery and targeted immunomodulation, offering a new antibiotic-free strategy for preventing and treating viral enteritis.