The role of microbiota derived peptidoglycan fragments in diseases and therapies
Berkel, Kevin van
MetadataShow full item record
The human gut microbiota, inhabited by diverse microorganisms, including bacteria, plays a pivotal role in maintaining our overall health. In its normal state, the human gut microbiota exhibits stability, resilience, and a mutually beneficial relationship with the host. Furthermore, it plays a crucial role in various physiological processes, such as metabolism, immune function, and nutrient absorption. Peptidoglycan fragments derived from the human gut microbiota, acting on immune receptors, are important in preserving this symbiotic relationship, but disruptions in this balance can lead to the onset of various diseases. This literature review aims to explore the potential link between peptidoglycan fragments and the development of different diseases. Additionally, it delves into the therapeutic applications of peptidoglycan. It has become evident that disturbances in peptidoglycan sensing, particularly involving NOD-like receptors (NLRs: NOD1 and NOD2) and peptidoglycan recognition proteins (PGLYRPs), contribute to intestinal dysbiosis and the emergence of several diseases, including Crohn's disease, neurodevelopmental disorders, and cardiovascular conditions. Notably, these disruptions also impact the development of cancer, especially colorectal cancer (CRC). However, peptidoglycan fragments exhibit a dual role, promoting tumorigenesis while also inhibiting it, for instance, by enhancing the effectiveness of PD-L1 anti-tumor immunotherapy. Consequently, peptidoglycan fragments used as therapeutics to enhance the efficacy of cancer immunotherapy hold promise for the future. Furthermore, the development of inhibitors targeting NLRs and PGLYRPs offers potential in slowing the progression of the aforementioned diseases. Patients suffering from conditions like Crohn's disease could potentially benefit from the utilization of probiotics, paraprobiotics, or fecal microbiota transplantation. These therapeutic implications, whether utilizing or inhibiting peptidoglycan or its immune receptors, offer promising prospects for the future. However, it is essential to underscore that further research is necessary to carefully weigh the benefits against the risks and ensure a balanced approach to disease management.