Preliminary exploration of the ability of HUC-MSCs to restore the lung microbiota and related metabolite disorders in IPF treatment: Combining 16S sequencing and metabolite analysis

ABSTRACT:

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive pulmonary disease, and effective therapies to reverse the natural course of IPF are lacking. A growing number of studies have shown that the use of human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) is a promising therapeutic strategy. However, the mechanism by which HUC-MSCs alleviate IPF and how HUC-MSCs affect the lung microbiota are still unclear and need further exploration.

Methods: Bleomycin (BLM) injection was utilized to establish a mouse model of IPF, followed by the application of 16S rDNA sequencing and LC‒MS/MS metabolomics to explore the underlying mechanism of HUC‒MSC treatment for IPF. Thirty mice were allocated into three groups, namely, the control, BLM, and BLM+HUC-MSC groups, and their lung morphology; the levels of α-SMA, FN1 and COL1A1; and the levels of the inflammatory cytokines TNF-α, IL-1β, IL-6, and TGF-β1 were subsequently evaluated. Bronchoalveolar lavage fluid (BALF) samples from six mice in each of the control, BLM, and BLM+HUC-MSC groups were collected randomly for 16S rDNA sequencing to analyze the lung microbiota and untargeted metabolomics.

Results: Compared with IPF model mice, HUC-MSCs restored alveolar morphology and reduced the expression of α-SMA, FN1 and COL1A1 and the inflammatory cytokines TNF-α, IL-1β, IL-6, and TGF-β1, confirming the anti-inflammatory properties of HUC-MSCs in IPF treatment. The findings from the 16S rDNA sequencing indicated that HUC-MSC treatment effectively decreased α diversity indices, such as ACE and Shannon indices, as well as β diversity, leading to a decrease in microbiota abundance. The findings from the metabolomics analysis revealed that the metabolites exhibiting notable differences were composed primarily of organic acids and their derivatives, lipids and lipid-like molecules, phenylpropanoids and polyketides, and organic nitrogen compounds, indicating the potential of HUC-MSCs to exert antifibrotic effects via these metabolic pathways.

Conclusions: Overall, our study preliminarily confirmed that IPF in mice was closely related to microbial and metabolic dysbiosis. HUC-MSC treatment modulated dysregulated metabolic pathways in mice with IPF, restoring abnormal microbiota function to that of the control group. This study provides new insights into the potential mechanisms and treatments of IPF.

INSTRUMENT(S): Liquid Chromatography MS - positive - HILIC, Liquid Chromatography MS - negative - HILIC

PROVIDER: MTBLS12922 | MetaboLights | 2025-09-01

REPOSITORIES: MetaboLights