Microfluidic-derived montmorillonite composite microparticles for oral codelivery of probiotic biofilm and postbiotics

Oral delivery of probiotics has shown promising effects in modulating the gut microbiota and treating ulcerative colitis (UC). However, the therapeutic efficacy is restricted by gastrointestinal assaults, poor mucosal adhesion, and single therapeutic modality. Here, we developed acid-resistant, gut-environment–responsive composite microparticles based on microfluidic electrospray for the oral codelivery of probiotic [ Lactobacillus acidophilus (LA)] biofilm and postbiotics (indole-3-propionic acid). Montmorillonite was selected for supporting biofilm formation due to its cation-exchange capability and clearly defined biosafety. The montmorillonite-LA biofilm was effectively protected by the microparticles and markedly improved the intestinal retention. Upon oral administration, the composite microparticles notably alleviated colitis in mice, including reducing the inflammatory response, improving intestinal barrier function, and modulating the gut microbiota. Consequently, the composite microparticles show high potential for enhancing probiotic delivery efficacy and present a promising strategy for UC treatment.