Postbiotics have emerged as a promising alternative to live probiotics, offering comparable health benefits while overcoming challenges related to safety, stability, and shelf life. This review provides a comprehensive overview of the current state of postbiotic research, beginning with updated definitions and the rationale for transitioning from live microbial formulations to inanimate postbiotics. We examine the diverse mechanisms by which postbiotics modulate host physiology, including enhancement of epithelial barrier function, immunomodulation, systemic metabolic regulation, neuroactive effects, anti‐inflammatory activities, and anticancer properties. Detailed discussions highlight how bioactive components—such as bacteriocins, exopolysaccharides (EPS), short‐chain fatty acids (SCFA), and specific proteins (e.g., Amuc_1100 and P9 from Akkermansia muciniphila )—mediate these effects through complex cellular signaling pathways and host‐microbe interactions. Furthermore, we review the antimicrobial potential of postbiotic formulations, emphasizing their role in controlling pathogenic and spoilage microorganisms. Various methods for microbial inactivation are discussed, ranging from conventional thermal techniques (e.g., pasteurization and ohmic heating) to non‐thermal approaches (e.g., ultrasonication, ionizing radiation, and ultraviolet light), as well as innovative hybrid methods that combine chemical, physical, and enzymatic treatments. These strategies not only ensure the complete inactivation of live microorganisms but also preserve the integrity and bioactivity of postbiotic compounds. Comparative analyses of live probiotics versus postbiotics reveal that inactivated formulations can deliver similar or even enhanced health benefits, with superior safety profiles and improved quality control. The review concludes by addressing current challenges in standardizing postbiotic definitions and production processes and by outlining future research directions necessary to unlock their full potential in clinical, nutritional, and biotechnological applications.

Although several internationally recognised scientific groups and non-governmental organisations have attempted to define ‘postbiotics,’ there remains no consensus. Leading experts have highlighted persistent problems of terminological inconsistency, lack of standardisation, and unclear boundaries between related concepts. What is needed is a comprehensive analysis that integrates existing definitions with considerations of manufacturing processes, mechanisms of action, and clinical applications. Ultimately, progress requires harmonisation of terminology to ensure comparability across studies and to provide a solid foundation for both academic and industry development.

Background: Recent studies on the lysate of Lactobacillus rhamnosus DV have demonstrated its antimicrobial and fungicidal activities. Classical microbiological methods for evaluating postbiotics and metabiotics are resource-intensive that need for new rapid and sensitive tests systems to assess their antimicrobial and antifungal properties. Objectives: The aim of this work was to study the effects of the Lactobacillus rhamnosus DV lysate on the intensity of Photobacterium phosphoreum bioluminescence and to demonstrate the potential use of bacterial bioluminescence to determine the bacteriostatic activity of this postbiotic substance. Materials and methods: The cell lysates of lactic acid bacterial strain L. rhamnosus DV were investigated, which were included in the Del-Immune V® dietary supplement produced by MirImmunoPharm LLC (Ukraine) in cooperation with Stellar Biotics, LLC (USA). The culture of P. phosphoreum IMV B-7071 was used in this study. Bioluminescence measurements were conducted using a digital photo-registration method. Bioluminescence was analyzed using cross-platform open-source software ImageJ (NIH) in brightness units in RGB color space. Results: The bioluminescence intensity initially increased with population density during the first day, then faded despite the continued growth of cell density in the bacterial suspensions. The addition of Lactobacillus rhamnosus DV lysate significantly suppressed bioluminescence, reducing it to background levels within 24 hours, with the effect varying by concentration. The peak luminescence in control samples occurred at 18 hours, whereas in lysate-treated samples it shifted to 3–6 hours, depending on the lysate concentration. Conclusions: The lysate of Lactobacillus rhamnosus DV causes a significant decrease in the growth rate of Photobacterium phosphoreum and strongly suppresses the intensity of their bioluminescence, the magnitude of which depends on the concentration of the lysate. This finding supports the use of bacterial luminescence as an effective way for evaluating the bacteriostatic activity of postbiotic substances against pathogenic and opportunistic microorganisms.