Probiotics are well recognized for their ability to modulate host immune responses; however, growing evidence indicates that many of their beneficial effects are mediated by structural components rather than by viable microorganisms. Among these components, probiotic-derived peptidoglycan has emerged as a key immunologically active molecule with a critical role in regulating both innate and adaptive immunity. Although substantial experimental data exist regarding its underlying mechanisms, the context-dependent immunomodulatory and anti-inflammatory functions of peptidoglycan have not been comprehensively integrated. In this review, we provide an up-to-date and comprehensive overview of the molecular and cellular mechanisms that govern the immunoregulatory properties of probiotic-derived peptidoglycan. We first discuss the structural diversity and processing of peptidoglycan and their implications for host recognition via pattern-recognition receptors, particularly Toll-like receptor 2 (TLR2) and nucleotide-binding oligomerization domain proteins 1 and 2 (NOD1/2). We then critically evaluate current evidence supporting the therapeutic potential of probiotic-derived peptidoglycan in infectious diseases, inflammatory bowel disease (IBD), autoimmune disorders, allergic inflammation, and cancer. Collectively, these findings suggest that peptidoglycan holds considerable promise for the development of next-generation microbiota-based immunotherapeutic strategies.
Keywords: cancer; immune modulation; infection; inflammation; inflammatory bowel disease (IBD); nucleotide-binding oligomerization domain (NOD) receptor; probiotic-derived peptidoglycan; toll-like receptor (TLR).
Copyright © 2026 Allela, Shareef, Sameer, Yaseen, Athab and Adil.