Probiotic spore‐based bioresponsive drug delivery for reversing inflammatory bowel disease and its associated anxiety and depression

Abstract Patients with inflammatory bowel disease (IBD) often exhibit gut microbiota dysbiosis and are predisposed to psychiatric disorders such as anxiety and depression. Consequently, developing novel oral probiotic therapies to address intestinal inflammation, microbiota dysbiosis, and psychiatric comorbidities is essential for managing IBD. Here, we propose a probiotic spore‐based bioresponsive system (BCS‐Que@ApNPs) fabricated by thioketone linkage of Quercetin‐loaded Antheraea pernyi (AP) silk fibroin nanoparticles (Que@ApNPs) to the Bacillus coagulans spores (BCS). The AP silk fibroin with arginine‐glycine‐aspartate (RGD) tripeptides in Que@ApNPs nanoparticles is critical for bioresponsive targeting Quercetin (Que) delivery to the inflamed intestinal epithelium. BCS could effectively shield probiotics from gastric acid‐induced degradation, maintaining their bioactivity in the intestinal tract, where they modulate the gut microbiota and preserve the integrity of the intestinal barrier. Notably, BCS‐Que@ApNPs can inhibit neuroinflammation and enhance hippocampal neural plasticity in the IBD mice model. Additionally, behavioral test results reveal that BCS‐Que@ApNPs alleviate IBD‐associated anxiety and depressive behaviors. This work provides a bioresponsive probiotic drug hybrid delivery system, highlighting a gut‐brain axis intervention therapeutic strategy for individuals diagnosed with IBD and its associated anxiety and depression.