A new horizon of precision medicine: combination of the microbiome and extracellular vesicles

Abstract

Over several decades, the disease pattern of intractable disease has changed from acute infection to chronic disease accompanied by immune and metabolic dysfunction. In addition, scientific evidence has shown that humans are holobionts; of the DNA in humans, 1% is derived from the human genome, and 99% is derived from microbial genomes (the microbiome). Extracellular vesicles (EVs) are lipid bilayer-delimited nanoparticles and key messengers in cell-to-cell communication. Many publications indicate that microbial EVs are both positively and negatively involved in the pathogenesis of various intractable diseases, including inflammatory diseases, metabolic disorders, and cancers. Microbial EVs in feces, blood, and urine show significant differences in their profiles between patients with a particular disease and healthy subjects, demonstrating the potential of microbial EVs as biomarkers for disease diagnosis, especially for assessing disease risk. Furthermore, microbial EV therapy offers a variety of advantages over live biotherapeutics and human cell EV (or exosome) therapy for the treatment of intractable diseases. In summary, microbial EVs are a new tool in medicine, and microbial EV technology might provide us with innovative diagnostic and therapeutic solutions in precision medicine.

Fig. 1. Biogenesis of extracellular vesicles (EVs) derived from eukaryotic cells and prokaryotic cells.

Extracellular vesicles can be classified into three main classes: Exosome, exosomes are formed within the endosomal network and released upon fusion of multivesicular bodies (MVBs) with the plasma membrane. Ectosomes, ectosomes are produced by outward budding and fission of the plasma membrane. Apoptotic bodies, apoptotic bodies are released as blebs of cells by apoptosis. Eukaryotic cells can release exosomes, ectosomes, and apoptotic bodies, whereas prokaryotic cells are able to secrete ectosomes and apoptotic bodies.

Fig. 2. Key milestones of microbial EV research.

The main findings of such studies are that gram-negative bacteria release EVs, bacterial EVs contain DNA and RNA, and gram-positive bacteria release EVs. Currently, microbial EV-based biotechnology is developing dramatically.

Fig. 3. Application of microbial EVs for precision medicine.

Precision medicine goals, including risk assessment, screening, prediction, and monitoring, are based on analysis using an artificial intelligence (AI) algorithm through human microbial EV big data and clinical data. High-risk individuals and diseased individuals can be identified by risk assessment, and preventive therapy can reduce disease risk. Diseased individuals identified by screening and diagnosis are suggested therapeutics based on the results of response prediction and monitoring. These processes can realize microbial EV-based health care solutions.