Preclinical Evaluation of Bacterial Lysates in Murine Disease Models: A Systematic Review.

BACKGROUND

Bacterial lysates are biologically active preparations obtained by thermal, mechanical, or chemical inactivation of whole bacterial cells, preserving their immunomodulatory properties.

METHODS

This systematic review evaluates preclinical studies published between 2010 and 2025 that investigated bacterial lysates in murine disease models, according to the PRISMA 2020 guideline. A total of 34 original studies met the inclusion criteria. The included studies cover a wide spectrum of pathologies, with respiratory infections and allergic/asthmatic diseases representing the most extensively investigated areas, followed by recurrent urinary tract infections, inflammatory bowel disease, acute lung injury/fibrosis, neuroinflammation, and cancer. Lysates ranged from monobacterial preparations to complex polybacterial formulations (particularly OM-85), administered orally, intranasally, or systematically.

RESULTS

Key mechanisms include activation of TLRs and NOD receptors, modulation of the NLRP3 inflammasome, T-cell polarization, macrophage remodeling, and induction of trained immunity. Beneficial effects were consistently reported, including reduced allergic inflammation, protection against recurrent infections, barrier restoration, and potentiation of anticancer immunotherapy.

CONCLUSIONS

The most robust and translationally advanced evidence remains that obtained in respiratory infection models, the original clinical indication of bacterial lysates. Clinical translation is still limited by preparation heterogeneity, lack of standardization, differences between murine and human immunity, and predominance of preventive study designs. Methodological standardization and rigurous bridging studies are needed to realize the therapeutic potential of bacterial lysates.

TRIAL REGISTRATION: PROSPERO (ID: CRD420261282071).