Current clinical treatments for inflammatory bowel disease with comorbid depression and anxiety show poor overall efficacy. The lack of targeted therapies often results in treatment discontinuation, incomplete symptom relief and higher relapse rates. Standard systemic anti-TNF-α therapy can partially relieve intestinal inflammation, yet it causes systemic immune suppression and elevated infection risks. Critically, it cannot reverse intestinal flora imbalance and gut-brain axis dysfunction, the core pathological factors behind IBD-related mental complications.
Intestinal flora mediates bidirectional signal communication between the intestine and the central nervous system, and gut microbial imbalance is a major trigger of depressive and anxiety symptoms in IBD patients. As symbiotic microbes naturally colonize the intestine, genetically engineered bacteria serve as an effective living treatment platform to regulate the intestinal microenvironment and target intestinal-derived mental disorders. Despite limited large-scale technical application at present, this innovative approach has broad clinical prospects and high research value.
Based on its mature technical system in intestinal microenvironment regulation and advanced biomaterials, the research team led by Prof. Guangjun Nie and Jiaqi Xu developed a clinically promising live therapeutic agent named engineered Escherichia coli Nissle 1917. This platform can actively target inflamed intestinal lesions for in-situ treatment and reshape intestinal flora, effectively solving the key limitations of traditional biological drugs and providing a new strategy for treating IBD-related mental comorbidities.
The study has two core innovations. First, the engineered strain secretes outer membrane vesicles loaded with anti-TNF-α nanobodies, which precisely block local intestinal inflammatory signals, repair intestinal mucosa and regulate local immune responses specifically in inflamed intestinal tissues. Second, it regulates the gamma-aminobutyric acid metabolism of intestinal flora. The engineered bacteria promote the proliferation of beneficial lactobacillus and increase circulating gamma-aminobutyric acid levels to restore intestinal microbial balance.
Science Bulletin
Experimental study