Akkermansia muciniphila (Akk) has gained significant attention for its role in regulating metabolic health and its impact on diseases such as cancer, diabetes, obesity, and inflammatory bowel disease (IBD). Studies suggest that the regulatory effects of Akk are primarily realized through its secreted extracellular vesicles (Akk-EVs), rather than relying solely on the in vivo form. These highly stable bilayer vesicles can regulate physiological and pathological processes in host cells through local or systemic signaling. Unlike direct delivery by live bacteria, Akk-EVs can efficiently deliver a variety of bioactive molecules involved in the regulation of glucose metabolism, lipid homeostasis, intestinal immunity, and maintenance of intestinal barrier integrity without the risk of infection. Given that natural and engineered EVs are increasingly entering clinical trials, Akk-EVs, with their superior stability and specificity, present a promising therapeutic alternative to live bacterial treatments. This review summarizes the regulatory mechanisms of Akk-EVs in health and disease and discusses their potential applications in precision medicine and clinical therapy, offering new insights into therapeutic strategies for metabolic disorders, cancer, and gut diseases.

Von Willebrand disease (VWD) is caused by a quantitative or qualitative defect of von Willebrand factor (VWF). Despite its prevalence as the most common hereditary bleeding disorder and the associated morbidity, its diagnosis and classification remains a challenge. This is mainly attributed to the heterogeneity of the disorder, multi-faceted functions of VWF, limitations of diagnostic assays, and significant impacts of various patho-physiological processes on VWF. For the past few years, significant progress has been made in elucidating the structural basis of VWF activation and development of VWF activity assays. The O-glycosylated sequences flanking the VWF A1 domain constitute a discontinuous and force-sensitive autoinhibitory module (AIM), which regulates the VWF affinity for GPIbα. New options for laboratory assessment of VWF activity include VWF∶GPIbM and VWF∶GPIbNab. The former utilizes a recombinant gain-of-function GPIbα fragment that supports spontaneous binding to plasma VWF, with less variability and higher precision compared to the traditional ristocetin cofactor activity assay. The latter utilizes a VWF-activating nanobody targeting the AIM to activate VWF, demonstrating the highest sensitivity for high-molecular-weight multimers among contemporary assays in the preliminary study. In this review, we focused on recent developments in the field of VWD diagnosis and considered how these advances can improve diagnostic algorithms and patient care in clinical practice.