Bacterial Extracellular Vesicles in Gastrointestinal Tract Cancer: An Unexplored Territory

Abstract

Bacterial extracellular vesicles are membrane-enclosed, lipid bi-layer nanostructures that carry different classes of biomolecules, such as nucleic acids, lipids, proteins, and diverse types of small molecular metabolites, as their cargo. Almost all of the bacteria in the gut secrete extracellular vesicles to assist them in competition, survival, material exchange, host immune modulation, infection, and invasion. The role of gut microbiota in the development, progression, and pathogenesis of gastrointestinal tract (GIT) cancer has been well documented. However, the possible involvement of bacterial extracellular vesicles (bEVs) in GIT cancer pathophysiology has not been given due attention. Studies have illustrated the ability of bEVs to cross physiological barriers, selectively accumulate near tumor cells, and possibly alter the tumor microenvironment (TME). A systematic search of original published works related to bacterial extracellular vesicles on gastrointestinal cancer was performed for this review. The current systemic review outlines the possible impact of gut microbiota derived bEVs in GIT cancer in light of present-day understanding. The necessity of using advanced sequencing technologies, such as genetic, proteomic, and metabolomic investigation methodologies, to facilitate an understanding of the interrelationship between cancer-associated bacterial vesicles and gastrointestinal cancer is also emphasized. We further discuss the clinical and pharmaceutical potential of bEVs, along with future efforts needed to understand the mechanism of interaction of bEVs in GIT cancer pathogenesis.

Sturgeon Chondroitin Sulfate Restores the Balance of Gut Microbiota in Colorectal Cancer Bearing Mice

“…After SCS treatment (High group), the relative abundance of Fusobacteria decreased by ~100-fold. Fusobacteria are common human pathogens, can participate in a variety of infections, such as appendicitis and inflammatory bowel disease [ 26 , 27 ]. Recent studies found Fusobacteria can promote colon tumor formation in animal models, and is abnormally enriched in colon cancer patients [ 28 ].…”

Microbiota and Extracellular Vesicles in Anti-PD-1/PD-L1 Therapy

“…The nanosized and non-replicative status of bEVs, their ability to be bioengineered to produce desired effect [ 106 , 107 ], their accumulation near the tumor sites, their capacity to induce anti-tumor immune responses [ 15 , 108 ], and their ability to carry the desired payloads [ 109 , 110 ] provide lucrative incentives for the further study of bEVs in order to fill the current knowledge gap as well as to develop optimized novel cancer therapy modules ( Figure 6 ).…”

“…The systematically released bEVs could then trigger tolerogenic immune reprogramming of the TME, thereby acting as tumor-promoting entities, and could also traverse to distant tissues and organs [ 14 ]. In contrast, bEVs derived from certain gram-negative bacteria such as Vibrio cholera , Escherichia coli (BL21), and Shigella flexneri have been found to significantly inhibit tumor growth when injected into colon tumor-bearing mice [ 15 ]. Consequently, bEVs present a promising prospect for further comprehending carcinogenesis and disease progression, improving existing immunotherapies, and formulating new targeted therapies.…”

Metabolomics of Extracellular Vesicles: A Future Promise of Multiple Clinical Applications

“… 22 As it aids in our understanding of molecular mechanism diversity, metabolomics can also be applied to precision medicine to improve human health, such as for metabolic and cardiac diseases, cancer, longevity, and nervous system diseases. 23 , 24 Additionally, due to the interference of environmental enzymes, initial genomics and transcriptomics are not completely linear with the downstream metabolites, as side reactions may simultaneously happen, resulting in unexpected products. 25 It is thus not enough to concentrate solely on the genomics and transcriptomics, as the whole molecular landscape should be understood.…”