Abstract
Ochratoxin A (OTA), a nephrotoxic, immunosuppressive, and potentially carcinogenic mycotoxin produced by Aspergillus and Penicillium species, poses a persistent threat to global food safety and livestock health. Although current biological detoxification strategies can degrade OTA, they often overlook its detrimental impact on vaccine efficacy, and safe probiotic candidates with dual functions of detoxification and immune restoration remain scarce. In this study, we isolated 3 OTA-degrading bacterial strains from 28 types of traditional Chinese fermented foods. Among them, Lysinibacillus macroides 38352 exhibited the highest degradation efficiency, removing 51.4% of 2.5 µg/mL OTA within 72 h at 37°C, with further increases observed over time. Mechanistic analysis revealed that the degradation was mediated not by cell surface adsorption but by secreted metabolites generated through active cellular metabolism. The strain also demonstrated excellent probiotic properties, including tolerance to pH 2-12 and 0.2% bile salts, sensitivity to 15 antibiotics (indicating no resistance), and no pathogenicity in mice. Notably, oral administration of L. macroides 38352 significantly reversed OTA-induced immunosuppression, enhancing vaccine-induced specific IgG, neutralizing antibody titers, and cytokine levels (interleukin [IL]-1β, IL-4, IL-12, IL-17, and interferon gamma), while also reducing inflammatory damage and improving growth performance in OTA-exposed broilers. Our study demonstrates that L. macroides 38352 is a dual-function probiotic capable of both OTA biodegradation and immune restoration. These findings provide a mechanistically distinct microbe-based strategy that couples mycotoxin detoxification with host immune restoration, advancing microbiome-informed interventions for sustainable livestock production and food safety. IMPORTANCE: Ochratoxin A (OTA) is a widespread food and feed contaminant known for its toxic, carcinogenic, and immune-disrupting effects, which pose serious challenges to animal health and food security. However, existing detoxification approaches rarely address the immune damage caused by OTA, and safe microbial solutions with both detoxifying and immune-supporting capabilities remain limited. This study introduces Lysinibacillus macroides 38352, a newly identified probiotic from traditional Chinese fermented food, as a dual-function candidate that not only degrades OTA efficiently through secreted metabolites but also helps repair immune function suppressed by OTA exposure. The strain shows excellent safety features and effectively improves vaccine responses and overall health in poultry. These findings highlight a novel microbe-based strategy that integrates mycotoxin detoxification with immune restoration, advancing the development of functional probiotics for microbiome-driven interventions in sustainable animal production and food safety.