Fecal microbiome extract downregulates the expression of key proteins at the interface between airway remodelling and lung cancer pathogenesis in vitro

Gabriele De Rubis ¹, Keshav Raj Paudel ², Sukriti Vishwas ³

¹Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, Australia.
²Centre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney 2007, Australia; Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India.
³School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India.
⁴Department of Life Sciences, School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur 57000, Malaysia.
⁵Chitkara College of Pharmacy, Chitkara University, Rajpura, India; Centre of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates.
⁶Aerogen, IDA Business Park, Dangan, Galway H91 HE94, Ireland; School of Pharmacy & Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin D02 YN77, Ireland; School of Pharmacy & Pharmaceutical Sciences, Trinity College, Dublin D02 PN40, Ireland.
⁷Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, Australia; School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India.
⁸Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, Australia; School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India; School of Medical and Life Sciences, Sunway University, 47500 Sunway City, Malaysia.
⁹Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, Australia; Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India.

⁰Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, Australia.

Pathology, Research and Practice +

|

June 13, 2024

View abstract on PubMed

Summary

Fecal microbiome extract shows potential in treating lung cancer by targeting airway remodeling pathways common in chronic respiratory diseases. This approach may improve outcomes for patients with both conditions.

Area Of Science

Oncology
Pulmonology
Microbiome research

Background

Lung cancer (LC) is a leading cause of cancer mortality with poor survival rates, often linked to treatment resistance and late diagnosis.
Patients with chronic respiratory diseases (CRDs) like asthma and COPD have a higher incidence of LC, sharing common features such as chronic inflammation and airway remodeling.
Airway remodeling involves fibrosis, epithelial-to-mesenchymal transition (EMT), and collagen deposition, processes also crucial in LC development.

Purpose Of The Study

To investigate the therapeutic potential of rat fecal microbiome extract (FME) on lung adenocarcinoma cells.
To explore the role of airway remodeling pathways in the connection between CRDs and LC.
To identify novel treatment strategies targeting shared pathophysiological mechanisms.

Main Methods

In vitro testing of rat fecal microbiome extract (FME) on A549 human lung adenocarcinoma cells.
Analysis of protein expression changes following FME treatment.
Focus on proteins involved in both airway remodeling and LC pathogenesis.

Main Results

FME treatment significantly downregulated the expression of six key proteins: Snail, SPARC, MUC-1, Osteopontin, MMP-2, and HIF-1α.
These proteins are critical at the intersection of airway remodeling and lung cancer development.
Demonstrated a potential therapeutic effect of FME on lung cancer cells.

Conclusions

Fecal microbiome extract exhibits in vitro therapeutic activity against lung adenocarcinoma cells.
FME targets key proteins involved in airway remodeling, suggesting a novel treatment avenue for lung cancer.
This study provides proof-of-concept for targeting airway remodeling mechanisms in lung cancer, particularly in CRD patients.

Keywords:

Airway remodelling Anticancer treatment Chronic respiratory diseases Fecal microbiome Lung cancer