Microfluidic-based multifunctional microspheres for enhanced oral co-delivery of probiotics and postbiotics

Probiotic-based therapies have shown great potential in the prevention and treatment of many diseases by positively regulating intestinal flora homeostasis. However, the efficacy of oral probiotics is severely limited due to the loss of bioactivity, short intestinal retention time, and insufficient therapeutic effect. Here, based on droplet microfluidics, we developed a hydrogel microsphere with colonic targeting and mucoadhesive capabilities as a multifunctional delivery platform, which can be used for co-delivery of probiotics (Escherichia coli Nissle 1917, EcN) and auxiliary molecules (indole-3-propionic acid, IPA), achieving synergistic therapeutic effects. In vivo studies shown that the integrated multifunctional microspheres can significantly reduce intestinal inflammation, repair intestinal barrier function, enhance probiotic colonization in the intestine, and modulate disordered intestinal flora, demonstrating enhanced therapeutic effects in a mouse model of colitis. This work reveals that microfluidic-based smart droplet microspheres can provide a versatile platform for advanced microbial therapies.