The immunomodulatory role of postbiotics and parabiotics: a narrative review of next-generation probiotics

Background Traditional live probiotics present profound translational challenges, including manufacturing instability and systemic safety risks in immunocompromised patients. To overcome these constraints, non-viable alternatives—namely postbiotics and parabiotics—have emerged as promising biologically active components within the framework of next-generation probiotics (NGPs). Objective This study reviews current clinical and preclinical evidence regarding the molecular mechanisms and therapeutic efficacy of postbiotics and parabiotics in modulating the host’s innate and adaptive immune responses. Methods PubMed, Web of Science, Scopus, and the Cochrane Library were systematically searched for eligible human and animal studies published up to May 2026 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Following rigorous screening and selection, a total of 11 studies that met the inclusion criteria were evaluated to assess the immunological outcomes associated with inanimate microbial fractions and metabolic byproducts. Results Findings indicate that parabiotic molecular pathways primarily rely on interactions between microbe-associated molecular patterns (MAMPs) derived from the cell wall and host pattern recognition receptors (PRRs), specifically Toll-like receptor 2 (TLR-2) and nucleotide-binding oligomerization domain-like receptors 1 and 2 (NOD1/NOD2). Concurrently, postbiotics (short-chain fatty acids, exopolysaccharides, and extracellular vesicles) downregulate pro-inflammatory cascades through nuclear factor-κB (NF-κB) inhibition and upregulate regulatory T cells (Tregs) through interleukin-10 (IL-10) induction. Conclusion By reducing bacterial translocation risks and horizontal antibiotic resistance gene transfer, while ensuring high techno-functional stability, postbiotics and parabiotics exert potent, reproducible immunomodulatory effects, establishing them as safe candidates for targeted biotherapeutic applications.