Microenvironment Self‐Adaptive Nanoarmor to Address Adhesion‐ and Colonization‐Related Obstacles in Impaired Intestine Promote Bacteriotherapy Against Parkinson's Disease

ABSTRACT Intestinal localized inflammations are recognized as key contributors to the incidence and progression of diverse extraintestinal disorders. Probiotic colonization has been increasingly highlighted for its potential to modulate susceptibility and progression of such diseases. Considering the adhesion‐ and colonization‐related challenges posed by multiple physiological and pathological characteristics in the intestine, a microenvironment self‐adaptive nanoarmor is developed. Partially acetylated chitosan oligosaccharides (CS) were employed to tune the adaptability and responsiveness of nanoarmor, enabling efficient interaction with the intestinal interface under dynamic conditions. Notably, Chitinase‐3‐like protein 1 (CHI3L1), an inflammation‐related secreted glycoprotein, served as a colonized niche to facilitate probiotics colonization in pathological microenvironments by leveraging the specific interaction between chitin‐like fragment and CHI3L1. By combining the intestinal microenvironment self‐adaptive nanoarmor with the inherent anti‐inflammatory properties of Lactobacillus plantarum ST‐III ( L. plantarum ), the nanocoated bacteria demonstrated significantly improved performance in alleviating intestinal mucosal inflammation, restoring gut barrier integrity, and reestablishing microbial homeostasis. Furthermore, the nanocoated bacteria showed significant therapeutic potential in treating Parkinson's disease (PD), a model for extraintestinal disorders, as evidenced by their ability to improve motor behavior disorders, reduce dopaminergic neuronal death, and mitigate neuroimmune responses. This approach proposes new insights into the living therapeutics for the treatment of extraintestinal diseases.