Oral Bioinspired Peroxisome-Engineered Probiotics for Modulating Gut Microbiota Homeostasis and Alleviating Cardiac...

Area of Science:

• Biomedical Engineering
• Microbiology
• Cardiology

Background:

• Doxorubicin (DOX) chemotherapy causes severe cardiotoxicity, limiting its use.
• DOX disrupts the gut barrier and microbial balance, impacting heart health via the gut-heart axis.
• Natural probiotics struggle with survival in the gastrointestinal tract, hindering their therapeutic potential.

Purpose of the Study:

• To develop an orally administrable bioinspired peroxisome engineered probiotic (BPEP) platform.
• To enhance probiotic survival and efficacy in mitigating doxorubicin-induced cardiotoxicity.
• To investigate the role of the gut-heart axis in chemotherapy-related cardiac damage.

Main Methods:

• Ruthenium-based nanozymes with antioxidant activity were encapsulated in lipid shells (bioinspired peroxisomes, BP).
• BPs were anchored onto *Escherichia coli* Nissle 1917 to create BPEP.
• BPEP was administered orally to a chronic DOX-induced cardiotoxicity mouse model.

Main Results:

• BPEP demonstrated enhanced survival and colonization in the gastrointestinal tract.
• BPEP treatment reduced oxidative stress, preserved intestinal barrier integrity, and restored microbial homeostasis.
• Oral BPEP administration significantly improved cardiac function in the mouse model.

Conclusions:

• BPEP represents a promising therapeutic platform for mitigating chemotherapy-induced cardiotoxicity.
• The bioinspired probiotic-nanozyme hybrid strategy overcomes limitations of natural probiotics.
• Targeting the gut-heart axis via BPEP offers a novel approach to cancer therapy side effect management.