Engineering fucoxanthin-loaded probiotics' membrane vesicles for the dietary intervention of colitis

Extracellular vesicles (EVs) are very attractive as carriers of active components due to their good immunological and their ability to penetrate the physiological barrier that synthetic delivery carriers cannot penetrate. However, the low secretion capacity of EVs limited its widespread adoption, let alone the lower yield of EVs loaded with active components. Here, we report a large-scale engineering preparation strategy of synthetic probiotic membrane vesicles for encapsulating fucoxanthin (FX-MVs), an intervention for colitis. Compared with the EVs naturally secreted by probiotics, the engineering membrane vesicles showed a 150-fold yield and richer protein. Moreover, FX-MVs improved the gastrointestinal stability of fucoxanthin and inhibited H₂O₂-induced oxidative damage by scavenging free radicals effectively (p < 0.05). The in vivo results showed that FX-MVs could promote the polarization of macrophages to M2 type, prevent the injury and shortening of colon tissue (p < 0.05), and improve the colonic inflammatory response. Consistently, proinflammatory cytokines were effectively suppressed after FX-MVs treatment (p < 0.05). Unexpectedly, such engineering FX-MVs could also reshape the gut microbiota communities and improve the abundance of short-chain fatty acids in the colon. This study lays a foundation for developing dietary interventions using natural foods to treat intestinal-related diseases.