Complementary Use of Probiotics and Their Antimicrobial Proteins in Brucellosis: A Comprehensive Review of Mechanisms and Clinical Benefits.

Brucellosis, a chronic intracellular infection caused by Brucella spp., remains therapeutically challenging due to antimicrobial resistance and frequent relapse. Probiotic microorganisms produce antimicrobial proteins-including bacteriocins and thermostable peptides-that inhibit pathogen viability, modulate host immunity, and attenuate oxidative damage. In murine models, therapeutic administration of Lactobacillus-based probiotics reduced Brucella infection index by 58.75%, while prophylactic use yielded a 25% reduction. Co-treatment with rifampicin eliminated residual infection, outperforming antibiotics alone. Experimental and clinical data suggest probiotics enhance antioxidant markers-e.g., lower malondialdehyde and higher total glutathione-while modulating cytokine profiles toward Th1-skewed immunity, with increased IFN-γ and regulated IL-10. Pediatric trials report faster symptom resolution and improved oxidative balance under probiotic co-administration. Additionally, mucosal vaccines vectored by probiotic strains elicit strong IgA/IgG titers and T-cell responses, targeting Brucella antigens such as Omp16, Omp31, and SOD. Given the limitations of current antibiotic regimens and rising antimicrobial resistance, probiotic-based approaches could offer a promising adjunctive strategy. Despite preclinical promise, no phase III trials exist evaluating probiotic-antibiotic synergy in human brucellosis. Future directions include standardized strain selection, mechanistic optimization, and multicenter randomized trials to enable clinical translation of probiotic-protein therapeutics in brucellosis.