ROS-responsive bio-hybrid probiotics for synergistic acute lung injury therapy

Area of Science:

• Microbiology
• Immunology
• Biomaterials Engineering

Background:

• Acute lung injury (ALI) involves severe inflammation and oxidative stress, leading to high mortality.
• Probiotics show potential for ALI treatment but have limited immune modulation and lung retention.
• Current strategies require enhanced delivery and localized therapeutic effects for effective ALI management.

Purpose of the Study:

• To engineer a probiotic bacterium for enhanced therapeutic effects in acute lung injury.
• To develop a dual-functional probiotic with immune regulation and antioxidant capabilities.
• To investigate the efficacy of the engineered probiotic in preclinical ALI models.

Main Methods:

• Engineered Lactobacillus paracasei to secrete interleukin-4 (IL-4) using synthetic biology.
• Modified bacterial surface with materials to enhance reactive oxygen species (ROS) scavenging.
• Evaluated in vitro suppression of TNF-α, IL-6, and ROS.
• Assessed therapeutic effects in LPS- and Pseudomonas aeruginosa -induced ALI mouse models.
• Utilized metabolomic profiling to analyze pulmonary microenvironment changes.

Main Results:

• Engineered probiotic suppressed pro-inflammatory cytokines (TNF-α, IL-6) and reduced intracellular ROS in vitro.
• Treatment significantly attenuated lung inflammation and histopathological injury in ALI mouse models.
• Demonstrated improved lung function, indicated by reduced lung wet/dry ratio.
• Therapeutic benefits increased over time, and pulmonary metabolites were favorably altered.

Conclusions:

• Developed a synergistic probiotic strategy combining synthetic biology and responsive materials for ALI.
• Engineered probiotic effectively delivers targeted immune modulation and oxidative stress relief.
• This versatile platform shows potent therapeutic efficacy in ALI and potential for other inflammatory respiratory diseases.