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Reactive oxygen species-responsive prodrug nanomicelle-functionalized Lactobacillus rhamnosus probiotics for

Xinyue Zhang1,2, Shuyun Liu1,2, Rui Xin1,2

  • 1Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, Shandong, China. lq7080@ouc.edu.cn.

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Summary
This summary is machine-generated.

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.

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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.