Reactive oxygen species-responsive prodrug nanomicelle-functionalized Lactobacillus rhamnosus probiotics for amplified therapy of ulcerative colitis

Xinyue Zhang ^1,2, Shuyun Liu ^1,2, Rui Xin ^1,2

⁰Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, Shandong, China. lq7080@ouc.edu.cn.

Materials Horizons +

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April 29, 2025

View abstract on PubMed

Summary

This study developed plant-derived nanomicelles carrying 18β-glycyrrhetinic acid (18β-GA) to protect probiotics. This strategy effectively treats ulcerative colitis (UC) and associated depression by resolving inflammation and restoring gut microbiota.

Area Of Science

Gastroenterology and Immunology
Nanomedicine
Pharmacology

Background

Ulcerative colitis (UC) is characterized by oxidative stress and gut dysbiosis, impacting millions globally.
Current probiotic therapies for UC face limitations including low bioactivity and short gut retention.
UC is often associated with depression-like behaviors, suggesting a gut-brain axis connection.

Purpose Of The Study

To design novel plant-derived 18β-glycyrrhetinic acid (18β-GA) prodrug nanomicelles to enhance probiotic efficacy for UC treatment.
To investigate the capacity of these nanomicelles to resolve reactive oxygen species (ROS) and inflammation.
To evaluate the combined therapeutic effects on UC, gut microbiota restoration, and associated depression-like behaviors.

Main Methods

Development of 18β-GA prodrug nanomicelles derived from plants.
Oral administration of nanomicelles and probiotics (Lactobacillus rhamnosus GG - LGG) in a UC model.
Assessment of ROS levels, inflammatory markers, gut barrier integrity, and gut microbiota composition.
Evaluation of depression-like behaviors and neuroinflammation markers.

Main Results

Nanomicelles released 18β-GA at UC lesion sites, triggered by ROS, reducing inflammation and oxidative stress.
The improved microenvironment facilitated LGG to repair intestinal barrier and restore gut microbiota.
Combined therapy significantly alleviated UC symptoms and UC-associated depression-like behaviors by reducing microglial activation and neuroinflammation.

Conclusions

Plant-derived 18β-GA prodrug nanomicelles offer a promising strategy for enhancing oral probiotic therapy in UC.
This integrated approach demonstrates synergistic therapeutic effects, addressing both colitis and associated depression.
The study highlights a novel oral nanomedicine strategy for inflammatory diseases by combining natural small molecules with probiotics.