Nanoarmored Probiotic for Inflammatory Bowel Disease Bacteriotherapy via a Dual-Targeting Host-Microbiota...

Area of Science:

• Biomaterials Engineering
• Microbiology
• Immunology
• Gastroenterology

Background:

• Inflammatory bowel disease (IBD) is characterized by oxidative stress, chronic inflammation, and gut dysbiosis, posing therapeutic challenges.
• Current treatments for IBD often lack specificity and can have systemic side effects.
• Probiotics offer therapeutic potential but face limitations in survival and targeted delivery within the gastrointestinal tract.

Purpose of the Study:

• To engineer a robust, biomimetic nanoarmored probiotic platform for enhanced IBD treatment.
• To improve bacterial viability, achieve colon-specific delivery, and enhance therapeutic efficacy against IBD.
• To investigate the immunomodulatory and microbiota-reversing effects of the nanoarmored probiotic.

Main Methods:

• Mineralization of FDA-approved calcium carbonate (CaCO3) nanocoating onto luteolin-loaded Escherichia coli Nissle 1917 (EcN-Lut).
• In vitro assessment of bacterial viability under simulated gastrointestinal conditions and evaluation of reactive oxygen species (ROS) scavenging and cytokine modulation.
• In vivo efficacy testing in a DSS-induced murine colitis model, including disease severity assessment, colon length restoration, and histopathology.
• Transcriptomic and 16S rRNA sequencing to analyze host signaling pathways and gut microbiota composition.

Main Results:

• The nanocomposite EcN-Lut/CaCO3 exhibited a 100-fold increase in bacterial survival and potent ROS scavenging (~100%).
• In vitro studies showed downregulation of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-17A) and upregulation of IL-10.
• In vivo, EcN-Lut/CaCO3 significantly attenuated colitis, restored colon length by 57.30%, reduced disease activity index by 72.73%, and improved gut microbiota balance.
• Transcriptomic analysis revealed activation of beneficial metabolic pathways and suppression of key inflammatory pathways.

Conclusions:

• The biomimetic nanoarmoring strategy successfully transforms probiotics into resilient, multifunctional living therapeutics for IBD.
• The engineered EcN-Lut/CaCO3 platform demonstrates significant therapeutic potential by reducing inflammation, restoring gut homeostasis, and enhancing bacterial survival.
• This approach offers a promising, generalizable strategy for targeted treatment of IBD and other complex inflammatory disorders.