# Adipose-derived stem cell extracellular vesicles attenuate liver fibrosis via restoration of gut barrier function and modulation of gut microbiota

## TL;DR

This study shows that extracellular vesicles from adipose-derived stem cells can reduce liver fibrosis by improving gut barrier function and balancing gut bacteria.

## Contribution

The novel contribution is demonstrating that ADSC-EVs treat liver fibrosis by modulating the gut-liver axis through gut barrier restoration and microbiota regulation.

## Key findings

- ADSC-EVs reduced liver fibrosis by decreasing collagen and suppressing stellate cell activation.
- Treatment restored gut barrier integrity and reduced intestinal permeability.
- ADSC-EVs increased beneficial gut bacteria like Akkermansia muciniphila and elevated butyric acid levels.

## Abstract

Aim: Liver fibrosis (LF) is a major pathological stage that may progress to end-stage chronic liver injury but currently lacks effective treatment strategies. Previous studies have shown that adipose-derived stem cell extracellular vesicles (ADSC-EVs) play crucial roles in tissue repair, immune regulation, and anti-inflammatory effects. This study aims to elucidate the therapeutic effect of ADSC-EVs in LF and reveal their regulation mechanisms in gut-liver axis dysregulation.

Methods: The LF mouse model was established by intraperitoneal injection of diethylnitrosamine/CCl4. LF mice for ADSC-EV treatment received ADSC-EVs (200 μg per mouse) twice a week for three weeks. Then, hepatic function tests, liver and gut histopathology, and gut microbiota analyses were performed.

Results: ADSC-EVs effectively improved hepatic function, reduced collagen deposition and suppressed hepatic stellate cell activation, exhibiting potent anti-fibrotic potential in LF mice. Additionally, they significantly restored intestinal barrier integrity by reducing intestinal permeability and reinforcing the mucus barrier. Furthermore, ADSC-EV treatment regulated gut microbiota dysbiosis, increased the abundance of beneficial intestinal bacteria such as Akkermansia muciniphila. ADSC-EV intervention also elevated the level of butyric acid in cecal contents and significantly reduced systemic inflammation.

Conclusion: Our findings suggest that ADSC-EVs represent a promising novel therapeutic strategy for LF, promoting liver tissue repair, enhancing intestinal barrier function, and maintaining gut homeostasis to establish a virtuous circle within the liver-gut axis.