Plant Exosomal-like Nanoparticles in Cross-Kingdom Modulation of Gut Microbiota and Host Health

Plant exosomal-like nanoparticles (PELNs) have emerged as evolutionary conserved nanocarriers that facilitate complex cross-kingdom communication. These lipid-bilayer vesicles encapsulate diverse bioactive cargoes, including small RNAs, proteins, and secondary metabolites, which are capable of modulating the gut microbiota to influence host health. This review systematically examines the therapeutic potential of PELNs in managing inflammatory bowel disease (IBD), improving cancer therapy while reducing treatment toxicity, and regulating systemic metabolic and inflammatory disorders via gut-organ axes. Despite this progress, the clinical translation of PELNs faces several hurdles. These include a need for geographic diversification, specifically the exploration of untapped African botanical resources, and the development of triple-kingdom (plant–animal–bacteria) multi-omic frameworks. Furthermore, overcoming technical bottlenecks in functional engineering and scalable manufacturing is essential for developing the next generation of PELN-based therapeutics. By fostering global research partnerships and standardizing production protocols, PELNs are poised to provide transformative strategies for the treatment of major human diseases.