Overview of the immunomodulatory role of bacterial probiotic-derived peptidoglycan: from molecular insights to therapeutic application.

2026-02-26
Frontiers in microbiology 17
- Omer Qutaiba B Allela
- Abdulkareem Shareef
- Hayder Naji Sameer
- Ahmed Yaseen
- Zainab H Athab
- Mohaned Adil

PubMed: 41834851
DOI: 10.3389/fmicb.2026.1761985

Study Design

Type: Review
Methods: 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.

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.

Research Insights

Bifidobacterium plantarum→Improved Effectiveness in Inflammatory Bowel Disease
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
Effect
Beneficial
Effect size
Moderate
Bifidobacterium plantarum→Improved Immune Modulation
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.
Effect
Beneficial
Effect size
Moderate
Bifidobacterium plantarum→Improved Immunomodulation
probiotic-derived peptidoglycan has emerged as a key immunologically active molecule with a critical role in regulating both innate and adaptive immunity
Effect
Beneficial
Effect size
Moderate
Bifidobacterium plantarum→Reduced Inflammation
the context-dependent immunomodulatory and anti-inflammatory functions of peptidoglycan
Effect
Beneficial
Effect size
Moderate
Bifidobacterium plantarum→Reduced Inflammatory Bowel Disease Symptoms
Collectively, these findings suggest that peptidoglycan holds considerable promise for the development of next-generation microbiota-based immunotherapeutic strategies.
Effect
Beneficial
Effect size
Moderate
Lactobacillus acidophilus L-92→Improved Immune Function
growing evidence indicates that many of their beneficial effects are mediated by structural components rather than by viable microorganisms... probiotic-derived peptidoglycan has emerged as a key immunologically active molecule with a critical role in regulating both innate and adaptive immunity
Effect
Beneficial
Effect size
Moderate
Lactobacillus acidophilus L-92→Reduced Inflammatory Response
the immunoregulatory properties of probiotic-derived peptidoglycan... therapeutic potential of probiotic-derived peptidoglycan in infectious diseases, inflammatory bowel disease (IBD), autoimmune disorders, allergic inflammation, and cancer
Effect
Beneficial
Effect size
Moderate
Lactobacillus casei rhamnosus→Modulated Immune Response
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.
Effect
Beneficial
Effect size
Moderate
Lactobacillus casei rhamnosus→Reduced Inflammation
the context-dependent immunomodulatory and anti-inflammatory functions of peptidoglycan
Effect
Beneficial
Effect size
Moderate