Dual engineered bacteria improve inflammatory bowel disease in mice

Area of Science:

• Microbiology
• Immunology
• Gastroenterology

Background:

• Current inflammatory bowel disease (IBD) therapies, including engineered bacteria, often use single drugs, limiting efficacy.
• Expressing multiple drugs in one bacterial strain can burden the host, hindering therapeutic effectiveness.
• A dual-bacterial system offers a potential solution to enhance both therapeutic and probiotic functions for IBD treatment.

Purpose of the Study:

• To construct and evaluate a dual-bacterial, dual-drug expression system for treating inflammatory bowel disease (IBD).
• To simultaneously neutralize pro-inflammatory factors and enhance anti-inflammatory pathways using engineered probiotics.
• To assess the therapeutic efficacy and safety of this dual-bacterial system in an IBD model.

Main Methods:

• Engineered two probiotic bacteria, Escherichia coli Nissle 1917, to express and secrete anti-TNF-α nanobody and IL-10.
• Administered the dual-engineered bacteria orally to an IBD model.
• Assessed inflammatory cell infiltration, pro-inflammatory cytokine levels, gut fibrosis, and intestinal microbiota composition.

Main Results:

• Oral administration of engineered bacteria significantly reduced inflammatory cell infiltration in the colon.
• Pro-inflammatory cytokine levels were reduced following treatment with the dual-bacterial system.
• The treatment did not exacerbate gut fibrosis and demonstrated a moderating effect on intestinal microbes.

Conclusions:

• A dual-bacterial, dual-drug system effectively treats IBD by delivering combined anti-inflammatory agents.
• This engineered bacterial therapy reduces inflammation and positively modulates the gut microbiome.
• The developed system presents a novel and promising therapeutic approach for managing inflammatory bowel disease.