Mechanisms and Clinical Translational Prospects of the Microbiota–Gut–Lung Axis in Connective Tissue Disease-Associated Interstitial Lung Disease
- 1School of Clinical Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, China
- 2School of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, China
- 3Key Laboratory of Modern Chinese Medicinal Preparations, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004, China
Abstract
Connective tissue disease-associated interstitial lung disease (CTD-ILD) is one of the most severe pulmonary complications of connective tissue diseases, featuring rapid progression and heterogeneous prognosis. Early recognition and prognostic prediction remain substantial clinical challenges. Accumulating evidence indicates that the microbiota–gut–lung axis participates in key pathological cascades, including autoimmune dysregulation, chronic inflammatory activation, and tissue fibrotic remodeling, which provides new insights into the pathogenesis of autoimmune-mediated lung diseases. This review systematically summarizes regulatory mechanisms of CTD-ILD involving gut dysbiosis, intestinal mucosal barrier impairment, disturbed metabolism of short-chain fatty acids, bile acids, and tryptophan, and systemic immune imbalance. We further compare evidence and pathological discrepancies of gut–lung–axis disturbance across CTD subtypes: systemic sclerosis-associated interstitial lung disease (SSc-ILD), rheumatoid arthritis-associated interstitial lung disease (RA-ILD), systemic lupus erythematosus-associated interstitial lung disease (SLE-ILD), idiopathic inflammatory myopathy interstitial lung disease (IIM-ILD), and primary Sjögren’s syndrome-associated interstitial lung disease (pSS-ILD). We also highlight the translational potential of gut–lung axis-related biomarkers for screening and assessment, summarize targeted interventions and integrated Chinese–Western therapeutic regimens, and pinpoint major evidence gaps and methodological limitations. This review refines the inter-organ regulatory framework of CTD-ILD and offers scientific references for mechanistic investigation, precise clinical evaluation, and novel therapeutic development.
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BibTeX
@article{hu2026mechanisms,
title = {{Mechanisms and Clinical Translational Prospects of the Microbiota–Gut–Lung Axis in Connective Tissue Disease-Associated Interstitial Lung Disease}},
author = {Junxia Hu and Shiwen Ke and Lisha Mo and Guoshuang Zhu and Zenan Wu and Yingchong Chen},
journal = {Biomolecules},
year = {2026},
month = oct,
doi = {10.3390/biom16101525},
url = {https://www.mdpi.com/2218-273X/16/10/1525},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Mechanisms and Clinical Translational Prospects of the Microbiota–Gut–Lung Axis in Connective Tissue Disease-Associated Interstitial Lung Disease
AU - Junxia Hu
AU - Shiwen Ke
AU - Lisha Mo
AU - Guoshuang Zhu
AU - Zenan Wu
AU - Yingchong Chen
PY - 2026
DA - 2026/10/01
JO - Biomolecules
DO - 10.3390/biom16101525
UR - https://www.mdpi.com/2218-273X/16/10/1525
AB - Connective tissue disease-associated interstitial lung disease (CTD-ILD) is one of the most severe pulmonary complications of connective tissue diseases, featuring rapid progression and heterogeneous prognosis. Early recognition and prognostic prediction remain substantial clinical challenges. Accumulating evidence indicates that the microbiota–gut–lung axis participates in key pathological cascades, including autoimmune dysregulation, chronic inflammatory activation, and tissue fibrotic remodeling, which provides new insights into the pathogenesis of autoimmune-mediated lung diseases. This review systematically summarizes regulatory mechanisms of CTD-ILD involving gut dysbiosis, intestinal mucosal barrier impairment, disturbed metabolism of short-chain fatty acids, bile acids, and tryptophan, and systemic immune imbalance. We further compare evidence and pathological discrepancies of gut–lung–axis disturbance across CTD subtypes: systemic sclerosis-associated interstitial lung disease (SSc-ILD), rheumatoid arthritis-associated interstitial lung disease (RA-ILD), systemic lupus erythematosus-associated interstitial lung disease (SLE-ILD), idiopathic inflammatory myopathy interstitial lung disease (IIM-ILD), and primary Sjögren’s syndrome-associated interstitial lung disease (pSS-ILD). We also highlight the translational potential of gut–lung axis-related biomarkers for screening and assessment, summarize targeted interventions and integrated Chinese–Western therapeutic regimens, and pinpoint major evidence gaps and methodological limitations. This review refines the inter-organ regulatory framework of CTD-ILD and offers scientific references for mechanistic investigation, precise clinical evaluation, and novel therapeutic development.
SN - 2218-273X
ER -