Alessio Di Ciancia

Background/Objectives: Chronic lymphocytic leukemia (CLL) is characterized by marked clinical heterogeneity, underscoring the need for reliable biomarkers to improve diagnosis and risk stratification. Extracellular vesicles (EVs) represent promising liquid biopsy candidates because they reflect the molecular profile of their cells of origin. In CLL, CD200 is a well-established marker of tumor cells; its expression on EVs and its role as a CLL biomarker were poorly characterized. This study investigated the diagnostic and prognostic value of serum EVs in CLL. Methods: Serum EVs were isolated from 83 patients with CLL and 20 healthy subjects (HS). EV morphology, size, and concentration were assessed by transmission electron microscopy and nanoparticle tracking analysis. Flow cytometry was used to evaluate the expression of CD19, CD20, and CD200 on EVs, while digital PCR quantified EV-associated miR-93-5p, miR-125b-5p, miR-150-5p, and miR-484. Results: Compared with HS, CLL patients showed increased total EV counts and higher levels of CD19⁺, CD20⁺, CD200⁺, and CD19⁺/CD20⁺ EVs, together with enhanced CD20 and CD200 expression and reduced miR-93-5p, miR-125b-5p, and miR-484 levels. In contrast, EV-associated miR-150-5p levels were comparable between CLL patients and HS. EV features were correlated with clinical and biological characteristics, including disease stage, cytogenetic abnormalities, treatment, and time to treatment (TTT). Older age was associated with lower EV concentrations but higher CD20 and CD200 expression. Advanced-stage disease was characterized by smaller EVs with increased CD200 expression. Notably, elevated CD200⁺ EV levels and reduced CD19 expression were associated with shorter TTT and earlier treatment initiation. Conclusions: Multiparametric profiling identified distinct quantitative, phenotypic, and molecular features of CLL-derived EVs and revealed CD200 as a novel EV-associated biomarker. These findings support the clinical utility of serum EVs as a new valuable approach for CLL diagnosis, prognosis, and treatment prediction.

Short-chain fatty acids (SCFAs), such as butyrate, acetate, and propionate, are the result of microbial fermentation and have been demonstrated to exert anticancer effects in different experimental models. We systematically reviewed 27 studies on postbiotics in colorectal cancer models, enclosing a range of study types including cell lines, animal models, and organoids. Eight studies that focused specifically on SCFAs were identified and analyzed. SCFAs promoted apoptosis through caspase activation, influenced NF-κB and MAPK signaling, increased mucin expression, and strengthened barrier function. Butyrate has also been demonstrated to induce autophagy via LKB1–AMPK signaling. Studies using SCFA-containing supernatants showed similar effects, although the presence of multiple biomolecules limited attribution. Overall, these findings provide a robust foundation for further research, particularly in the context of translational studies that can bridge the gap between preclinical and clinical research.

Postbiotics, defined as a preparation of inanimate microorganisms and/or their components, including metabolic byproducts, have gained recognition as promising modulators of gut health and disease, offering advantages over probiotics in terms of safety, stability, and formulation. This systematic review investigates the therapeutic potential of postbiotics derived from functional foods in the context of colorectal cancer (CRC), a leading cause of cancer-related mortality worldwide. Despite encouraging preclinical findings, translation into clinical practice remains limited due to a paucity of robust human trials, revealing a significant gap and the need for further translational research. Key bioactive categories of postbiotics are described, alongside their anti-inflammatory, immunomodulatory, and chemopreventive mechanisms. Through comprehensive literature mapping, this review uniquely categorizes research according to the experimental models employed, i.e., in vitro, in silico, in vivo, and ex vivo, and advanced models such as organoids and organ-on-chip platforms. The latter offers greater physiological relevance by closely mimicking human tissue architecture and microenvironment. These models help demonstrate how postbiotics may influence tumorigenesis through mechanisms involving inflammation, apoptosis, epigenetic regulation, and the maintenance of gut barrier integrity. Finally, the review summarizes recent innovations in their delivery strategies and calls for comprehensive mechanistic studies and high-quality clinical trials to validate postbiotics as safe and effective adjuncts in CRC prevention, therapy, and management.

Postbiotics, defined as non-viable microbial cells, their components, or metabolic byproducts, have gained recognition as promising modulators of gut health and disease, offering advantages over probiotics in terms of safety, stability and formulation. This systematic review explores the therapeutic potential of postbiotics derived from functional foods in the context of colorectal cancer (CRC), a leading cause of cancer-related mortality worldwide. Key bioactive categories of postbiotics, including short-chain fatty acids, exopolysaccharides, enzymes, cell wall fragments and cell-free supernatants are described, along with their mechanisms of action such as anti-inflammatory, immunomodulatory, and chemopreventive effects. Particular emphasis is laid on preclinical studies, in vitro, in silico, in vivo, ex vivo and advanced models such as organoids and organ-on-chip systems, that demonstrate how postbiotics may impact on tumorigenesis through pathways involving apoptosis, epigenetic regulation and gut barrier integrity. Recent advances in postbiotic delivery strategies are also summarized. Despite encouraging preclinical results, translation to clinical practice remains limited by the scarcity of human trials. This review draws attention to the need for further mechanistic research and robust clinical studies to validate the role of postbiotics as safe, effective adjuncts in CRC prevention therapy and management.